Novichkov A. I., Diskin-Posner Y., Shimon L. J., Leitus G., Flamm C. & Semenov S. N. (2025) Journal of the American Chemical Society. 147, 37, p. 33711-33722
Although HCN has been explored extensively as a precursor in the prebiotic synthesis of biological molecules, macroscopic system-level phenomena, originating from reactions of HCN, such as autocatalysis, oscillations, pattern formation, and phase separation have attracted less attention. Autocatalysis and phase separation are particularly interesting in the context of the origin of life because they are sources of self-replication and compartmentalization. In this work, we investigate the reaction between HCN and cysteamine in water, which exhibits both sigmoidal reaction kinetics and the formation of a distinct liquid phase. We studied the origin of the sigmoidal kinetics using NMR spectroscopy and other techniques, investigated the chemical composition of the products using single-crystal X-ray diffraction and mass spectrometry, and probed the absorption of inert additives into the second liquid phase. Our studies show that the sigmoidal kinetics arise from an autocatalytic feedback loop driven by both an increase in pH and the catalytic nature of the newly formed phase itself. Product analysis revealed co-oligomers with a backbone derived from HCN and branches from cysteamine. This composition suggests that co-oligomerization with thiols provides a route to tractable oligomers, mitigating the formation of insoluble HCN polymers. Furthermore, this second liquid phase effectively sequesters hydrophobic molecules like benzene, demonstrating its capacity to act as a primitive compartment. The phenomena that we observed may provide some insight into prebiotic chemical networks and early-stage chemical evolution.
Wen Q., Tan M., Eisenberg O., Nasi H., Brumfeld V., Tiwari A., Ye H., Kahr B., Shimon L. J. W., Lahav M. & van der Boom M. E. (2025) Nature Communications. 16, 1, 8441
The expression of molecular dissymmetry in crystal form has been studied since Pasteur correlated macroscopic and microscopic chirality by measuring the optical activity of solutions of enantiomorphous tartrate salt crystals. Here, we show a direct correlation between enantiomorphous metal-organic framework (MOF) crystals and the chirality of the molecular structure. The geometry of the habits is correlated with single-crystal optical activity along the accessible low-symmetry directions. Weak X-ray scattering from small crystals was consistent with a hexagonal, enantiomorphous space group. However, the heterochirality of the mirror image forms could not be established with X-rays, necessitating a different approach. The optical circular birefringence of the enantiomorphs as evidenced by chiroptical imaging with a complete polarimetric microscope, was used to correlate optical and morphological chirality.
Aizen R., Vijayakanth T., Guerin S., Cazade P. A., Tiwari O. S., Xue B., Shimon L. J., Cao Y., Thompson D. & Gazit E. (2025) Chemistry - A European Journal. 31, 59, e00726
Metabolites, including amino acids, nucleobases, and vitamins, have emerged as promising candidates for sustainable functional materials due to their inherent biocompatibility and low fabrication costs. Notable examples include glycine-based nanogenerators, indigo-based organic transistors, and caffeine-based optical waveguides. Riboflavin (vitamin B2), forms optically active supramolecular structures in the tapetum lucidum of lemurs and cats; however, its detailed packing and functional role remain unknown. Here, aiming to explore the bio-inspired self-assembly of riboflavin to uncover potential device applications, we discovered and extensively characterized a new single co-crystal using a combination of crystallography, microscopy, and mechanical experiments supported by atomistic molecular models to understand the organization on different surfaces. The crystals exhibit pronounced surface responsiveness, leading to the formation of distinct branched, twisted, and serrated micron-scale morphologies as the riboflavin self-assembled on different substrates of copper, mica, and silicon. This intrinsic ability to adapt shape and generate substrate-templated structures was confirmed computationally and experimentally and was attributed mainly to the crystal's relatively low Young's modulus, reflecting its lattice flexibility. This structurefunction study of an adaptable metabolite crystal offers fundamental insights into how molecular organization governs mechanical responsiveness, advancing the understanding of bio-inspired crystallization and paving the way for future technological applications.
Yuan H., Tang Y., Naranjo E., Cazade P. A., Yao Y., Thangavel V., Yang R., Rencus-Lazar S., Thompson D., Shimon L. J., Wei G., Chen X. & Gazit E. (2025) Angewandte Chemie - International Edition. 64, 43, e202513629
Engineering guest-responsive materials capable of controlled and precise sorption behavior and structural deformation in response to external stimuli is imperative for various applications. However, existing systems often exhibit complex, unpredictable dynamics, posing challenges for efficient control and utilization. Here, we design crystalline metalpeptide frameworks with tunable water-responsive (WR) dynamics by assembling glycine-threonine (Gly-Thr, GT) or glycine-serine (Gly-Ser, GS) peptides with zinc (Zn) ions, achieving either continuous or discrete threshold water-sorption-dependent phase transitions. As ambient relative humidity (RH) changes, the Zn-GT crystal continuously adsorbs or desorbs water, resulting in gradual structural adaptations, similar to those observed in other supramolecular systems. In contrast, the Zn-GS crystal undergoes stepwise water sorption and structural transitions at specific RH thresholds. These contrasting WR modes arise from differences in water binding and structural dynamics; in Zn-GT, each coordinating water molecule contributes varying degrees of framework integrity and evaporates sequentially, whereas in Zn-GS, water molecules with comparable interactions within a flexible framework are released simultaneously during dehydration. Our study demonstrates the mechanism by which hostguest interactions can be harnessed to control dynamic sorption and actuation behavior of supramolecular materials at the molecular level, offering mechanistic insights that may guide the rational design of next-generation programmable, stimulus-responsive systems.
Dan Y., Arnon Z. A., Tang Y., Kravikass M., Zhou Y., Misra R., Tiwari O. S., Shimon L. J., Beck R., Gazit E., Wei G. & Adler-Abramovich L. (2025) Nature Communications. 16, 6106
Self-assembled supramolecular materials have gained extensive interest due to their ability to form structures with diverse physical, chemical, and biological properties. These characteristics arise from the precise arrangement of building blocks at the nanoscale. There is an unmet need to efficiently manipulate crystalline materials solid-state packing and monitor the effect on growth at a single crystal level. Herein, we used N-capped diphenylalanine peptide module to study the conditions affecting lattice configuration. In addition to the canonical monoclinic crystal, we found the peptide to alternatively assemble into an orthorhombic crystalline form. Wide-angle X-ray analysis indicated that the sharp transition between the distinct crystalline polymorphic forms depends on solvent composition, indicating the impact of the immediate molecular milieu on the monomeric conformation and the interactions with crystals. Both experimental and molecular dynamics simulations corroborate the results and demonstrate that solution composition directs the monomers to adopt specific conformations and affects their interactions with pre-formed crystal templates, resulting in either crystal growth, steady-state, or disassembly. These notions provide a profound understanding of crystal polymorphism and growth mechanisms at the molecular level, enabling the advanced design of bio-inspired materials.
Vishwakarma S., Tiwari O. S., Banerjee D., Shimon L. J. W., Israelstam A., Kaminker I., Mukherjee S., Gazit E. & Makam P. (2025) Advanced healthcare materials. 14, 24, 2501435
The quest for efficient, robust, and sustainable solutions in environmental remediation and advanced biosensing has catalyzed significant interest in biomimetic enzymology. Here, a new Bionanozyme, synthesized from a single nucleobase-adenine (A)-coordinated with copper (Cu) in a 2D crystalline structure (A-Cu), is presented. This state-of-the-art A-Cu Bionanozyme, inspired by natural redox enzymes (Laccase (LAC), Catechol oxidase (CO), and Peroxidase (POD)), is synthesized via simple and scalable, green methods including solvent-free co-grinding and natural aqueous evaporation process. A-Cu's unique structure exhibits triple-enzyme-mimicking catalytic activity, enabling it to detect and degrade toxic phenols in contaminated water and perform ultrasensitive colorimetric biosensing for key biomarkers like dopamine, hydrogen peroxide, and glutathione. Additionally, its biocompatibility and reactive oxygen species (ROS) scavenging properties highlight its potential in biomedical applications. Hence, this report provides a foundational framework for developing next-generation multienzyme-mimicking Bionanozymes with the potential to enhance eco-friendly technologies in both environmental and biomedical applications.
Banerjee D., Chibh S., Tiwari O. S., Mirón G. D., Monti M., Yakir H. R., Pawar S., Fixler D., Shimon L. J., Gazit E. & Hassanali A. (2025) Angewandte Chemie - International Edition. 64, 29, e202505331
Developing noninvasive techniques that can probe how solvents modulate the nucleation pathways of bioorganic molecules in solution remains an active and open area of research. Herein, we investigate the crystallization of the amino acid L-Cysteine and show that both the structure of the crystal and its intrinsic fluorescence can be drastically altered by the solvent. Crystals formed in heavy water exhibit markedly different intermolecular packing as well as strikingly different monomer conformations compared to those in light water. Remarkably, these differences in the supramolecular packing result in significantly elevated intrinsic fluorescence in the crystal that is formed in heavy water. Using a combination of experimental techniques and advanced electronic structure approaches, we elucidate the molecular interactions within the crystals that govern both the electronic origins and the intensity of their emission. These findings demonstrate how tuning the solvent by changing its isotope leads to the emergence of design principles for new intrinsic fluorophores that could serve as novel sensing probes for biomedical applications.
Deri S., Feller M., Panda S., Blank B., Iron M. A., Diskin-Posner Y., Avram L., Shimon L. J., Mondal R. & Gnaim S. (2025) Journal of the American Chemical Society. 147, 23, p. 19520-19529
We introduce a novel class of boranobornadiene derivatives, termed boranoanthracene, along with an in-depth study of their structures and reactivities. Using these versatile precursors, we propose a fundamentally novel mechanism for generating free oxoborane species. This pathway enables the formation of aminoxoborane species, which are rarely reported in the literature. The proposed mechanism unfolds via the coordination of an oxygen-Lewis base (dimethyl sulfoxide) to the boron center, triggering a fragmentation cascade propelled by oxidative aromatization. A detailed experimental analysis, NMR measurements, and DFT calculations provide a strong evidence supporting our findings. We explored three distinct reactivities of these species: first, the insertion of oxoborane species into B-C bonds, representing, to the best of our knowledge, the first example of this reactivity. Second, we demonstrated the [3 + 2] cycloaddition reaction of oxoboranes with nitrones, offering viable access to new boranoheterocycles. Third, we reported the first example of a [5 + 2] cycloaddition between oxoboranes and azomethine imines, leading to the formation of a seven-membered boracycle. The diverse reactivities and facile generation of aminoxoboranes highlight their immense potential as versatile tools in organic chemistry.
Pophali S., Su D. D., Ata R., Vijayakanth T., Nandi S., Jain R., Shimon L. J., Misra R. & Barboiu M. (2025) Journal of the American Chemical Society.
Transmembrane selective transport of metabolites controls essential biological functions. During the last two decades, artificial channels have been developed and cyclic peptides have emerged as ideal platforms for efficient ion, sugar, and nucleic acid channel translocation. Despite these tremendous developments, cyclic peptides have eluded selective water transport. Herein, we report the formation of narrow artificial β-helical tubules with diameters ranging from 2.80 to 3.25 Å that selectively control the water translocation, akin to natural aquaporin channels. The tubular assemblies resulted from the metal-driven folding and assembly of minimal heterochiral metal-binding 3-pyridyl-terminated peptides. The bent ultrashort peptide ligand coordinates with Ag<sup>+</sup> metal ions in a head-to-tail manner, which undergoes subsequent polymerization into a β-helical tubular structure stabilized by interstrand hydrogen bonds (H-bonds) between the β-strands and π-π staking interactions between terminal pyridyl moieties. Furthermore, sequence engineering of the heterochiral peptide and subsequent Ag<sup>+</sup> ion coordination of the tailored peptides enabled the formation of distinct synthetic double β-barrel and artificial β-helical tubular assemblies, with water molecules encapsulated in the hydrophilic core of the tubes. These water-encapsulated tubes were further explored as artificial water channels in lipid bilayers. Our findings suggest that such β-helical tubular channels achieve a single-channel permeability of 10<sup>6</sup> water molecules/second/channel, which is within 1-2 orders of magnitude lower than that of aquaporins, with a rather good ability to sterically reject ions and prevent proton transport. These assemblies present significant potential for engineering efficient membranes for water purification and separation sciences.
Dey S., Field E. H., Wang Y., Han K., Kumar R., Shimon L. J., Liu S., Guerin S., Berryman J. T., Ji W., Reynolds N. P. & Bera S. (2025) Small. 21, 18, 2500288
Although initially identified as pathological aggregates, amyloid fibrillar assemblies formed by various proteins and peptides are now known to have crucial physiological roles, carrying out numerous biological functions in almost all organisms. Due to unique features, the common etiology of amyloids cross-β structure is long posited as a template for designing artificial self-assembling systems. However, the recent discovery of cross-α amyloids indicates additional structural paradigms for self-assembly into ordered nanostructures, turning significant attention toward designing artificial nanostructures based on cross-α assembly. Herein, a minimalistic designer peptide which forms a hydrogen-bonded amyloid-like structure while remaining in the α region of conformation is engineered, to investigate the effect of aromatic, hydrophobic, and steric considerations on amyloidal assemblies. These results demonstrate a significant modulation of helicity and self-assembly, leading to the structure-dependent piezoelectric function of the amyloid-like cross-α fibrils. This study indicates a potential avenue for molecular engineering of functional peptide materials.
Malik N., Shimon L. J., Houben L., Kossoy A., Pinkas I., Kaplan-Ashiri I., Bendikov T., Lahav M. & van der Boom M. E. (2025) Chemistry - A European Journal. 31, 7, e202403577
The branched metal-organic frameworks (MOFs) are the first superstructures of this kind, and the growth mechanism may explain crystal shapes of other materials. The mechanism of the formation of fascinating structures having a hedrite, sheaf or spherulite appearance are detailed. The branching can be controlled, resulting in crystals that either exhibit multiple generations of branching or a single generation. These structures might result from an increasing number of defects on fast-grown rods. As the basal facets become less reactive, material is added to the prism facets, leading to secondary nucleation and triangular branches. These triangular structures are connected to the rod surface, growing longer than the central rod. Electron diffraction analyses show that the sheafs are polycrystalline structures with their fantails consisting of single-crystalline nanorods deviating gradually from each other in their orientation. The crystallographic structure consists of channels with opposite handedness. The accessibility of the nanochannels and the porosity of the superstructures are demonstrated by chromophore diffusion into the channels. The confinement and alignment of the chromophores inside the channels resulted in polarized-light dependent coloration of the crystals; the polycrystallinity generated areas having different optical properties.
Lu L., Luo J., Montag M., Diskin-Posner Y. & Milstein D. (2025) Journal of the American Chemical Society. 147, 49, p. 45283-45293
Alcohol coupling reactions that are induced by alcohol dehydrogenation, and generate hydrogen or water as the only byproducts, have become a well-recognized way to carry out important synthetic transformations, such as esterification and alkylation, in a green and atom-economical fashion. Herein, we report a new type of alcohol-alcohol coupling reaction that involves the dehydrogenative annulation of ethylene glycol with secondary alcohols to give 1,2-cyclopentanedione derivatives in a single synthetic step. This process, which is catalyzed by a pincer complex of earth-abundant manganese, represents a new approach for constructing structurally complicated products from inexpensive, readily available alcohols.
Pinsk N., Benshalom N., Hartstein M., Diskin-Posner Y., Menahem M., Hellman O., Kronik L. & Yaffe O. (2025) Journal of the American Chemical Society. 147, 45, p. 41699-41705
Hydrogen bonds in molecular crystals are often modeled as double-well potentials, yet direct evidence linking this potential form to vibrational spectroscopic features remains elusive. In this study, we investigate alpha-glycine, a hydrogen-bonded crystal that exhibits pronounced Raman anomalies without undergoing a structural phase transition. Through temperature- and polarization-dependent Raman spectroscopy, supported by isotope substitution and first-principles calculations, we identify two peaks whose behavior violates conventional Raman selection rules. These peaks merge and narrow anomalously with temperature, an effect that cannot be explained by harmonic models or thermal broadening. Simulated spectra based on a weakly evolving asymmetric double-well potential reproduce this merging, indicating that both peaks originate from one double-well potential. Our results establish alpha-glycine as a model system directly linking microscopic hydrogen-bond potentials to vibrational spectroscopic features.
You C., Lu L., Luo J., Diskin-Posner Y. & Milstein D. (2025) Journal of the American Chemical Society. 147, 33, p. 30060-30071
Liquid organic hydrogen carriers (LOHCs) offer an attractive strategy for efficient hydrogen storage and release, thereby facilitating the effective use of hydrogen as a carbon-neutral energy carrier. The advancement of LOHC technology is highly dependent on the innovation of the catalysts. Herein, based on a strategy combining rigidity and flexibility in a single molecular catalyst, a novel class of PNP-pincer ligands, called longshort-arm acridine ligands, and their Ru complexes have been developed and successfully used in the LOHC system based on ethylene glycol (EG). In comparison to previously reported catalytic systems, which suffered from low conversions or insufficient H<sub>2</sub>release due to the dual challenge of catalyst stability and catalytic activity in the acceptorless dehydrogenative coupling of EG, this new catalytic system overcomes these challenges and achieves high conversion (up to >99%) with high H<sub>2</sub>yield (up to 96%), achieving a hydrogen storage capacity of 6.2 wt %. Mechanistic and computational studies reveal that the special coordination mode, one 5-membered metallacycle and one 6-membered metallacycle, is essential for the high reactivity and late-stage dehydrogenative coupling. Moreover, both dehydrogenation and hydrogenation can be achieved under solvent- and additive-free conditions, highlighting the robustness and application potential of this new catalytic system. This advances the promising liquid-to-liquid paired LOHC systems based on inexpensive, widely accessible, and biobased EG toward practical application.
Niazov-Elkan A., Lee H. J., Mafi S., Yerragunta M., Rosenhek-Goldian I., Penedo M., Fantner G., Kossoy A., Feldman Y., Diskin-Posner Y., Oron D. & Vekilov P. G. (2025) iScience. 28, 7, 112866
How molecular-level understanding of the crystal growth mechanisms and their relation to lattice bonds informs the rational design of crystals with desired shapes and properties has remained elusive. Here we employ theophylline crystals and drive them into classical growth mode, in which the crystals grow molecule-by-molecule and new layers are generated by two-dimensional nucleation. We demonstrate that classical growth allows for controlling the crystal's shape and dimensions. We correlate the anisotropic responses to the supersaturation of the growth rates of crystal layers and crystal faces to the hydrogen and π−π stacking bond chains in the crystal lattice. The obtained insights suggest strategies to direct the crystal shape to either one-dimensional needles or flat sheets. Moreover, we show that crystals that grow by the classical mode of direct monomer incorporation have the potential to regrow and heal once a defect is introduced by mechanical cut or local thermal subliming of crystalline sections.
Liang Y., Luo J., You C., Diskin-Posner Y. & Milstein D. (2025) Nature Catalysis. 8, 2, p. 98-106, 5339
Using water as a hydrogen or oxygen source in organic synthesis has enabled various reductive and oxidative transformations, but incorporation of both hydrogen and oxygen atoms into the same molecule, representing an atom-economic and environmentally benign process, has scarcely been explored. Here we report a hydrogenative oxidation strategy using water as both a source of H<sub>2</sub> and formal oxidant, enabling the direct synthesis of lactams from N-heteroarenes and thereby eliminating the need for additional reductants and oxidants and minimizing waste generation. The reaction can be initiated either under low H<sub>2</sub> pressure or with a catalytic amount of H<sub>2</sub>, leading to the efficient transformation of various N-heteroarenes into lactams in excellent yield thanks to an in situ-generated, piperidine-based, ruthenium pincer complex that balances the hydrogenation and dehydrogenation processes. This study will promote the design of other hydrogenative oxidation reactions using water. (Figure presented.)
Nasi H., Barak D., di Gregorio M. C., Shimon L. J., Lahav M. & van der Boom M. E. (2024) Crystal Growth and Design. 24, 20, p. 8468-8475
Straight facets and sharp edges are among the most distinctive indicators of well-defined crystals and often reflect the polyhedral geometry and symmetry of the underlying close-packed, molecular structure. Curved morphologies are sometimes observed in biogenic crystals where templating or nonclassical crystallization processes (e.g., crystallization via amorphous states) occur. Here we report the formation and growth of copper-based metal-organic frameworks (MOFs) that crystallize in the hexagonal space group P622. The individual MOFs are homochiral and are formed from achiral compounds. The crystals begin as hexagonal-like structures, developing over time into complex flower-like structures having two decks joined in the center. Each deck layer has six well-defined petals with curved lateral surfaces. The growth mechanism shows initial straight petals that become progressively more curved with increased faceting. Remarkably, despite its multidomain appearance, the entire entity is a single crystal. The curved morphology is correlated to the crystallographic structure and the arrangement of nanosized channels within this structure. Crystal habits are typically considered to be inconsistent with curved morphologies. This work suggests that crystallographic explanations can support the development of such surfaces for low-density structures.
Raje S., Garhwal S., Młodzikowska-Pieńko K., Sheikh Mohammad T., Raphaeli R., Fridman N., Shimon L. J., Gershoni-Poranne R. & de Ruiter G. (2024) JACS Au. 4, 11, p. 4234-4248
With growing efforts pushing toward sustainable catalysis, using earth-abundant metals has become increasingly important. Here, we present the first examples of cobalt PC<sub>NHC</sub>P pincer complexes that demonstrate dual stereoselectivity for allyl ether isomerization. While the cationic cobalt complex [((PC<sub>NHC</sub>P)Co)<sub>2</sub>-μ-N<sub>2</sub>][BAr<sub>4</sub><sup>F</sup>]<sub>2</sub> (3) mainly favors the Z-isomer of the enol ether, the corresponding methyl complex [(PC<sub>NHC</sub>P)CoMe] (4) mostly gives the E-isomer. The dichotomy in selectivity was investigated computationally, revealing important contributions from the substituents on the metal (N<sub>2</sub> vs Me), including a 1,2-alkyl migration from cobalt to the N-heterocyclic carbene (NHC) of the methyl substituent, which is further explored in this report.
Bajpayee N., Pophali S., Vijayakanth T., Nandi S., Desai A. V., Kumar V., Jain R., Bera S., Shimon L. J. & Misra R. (2024) Chemical Communications. 60, 19, p. 2621-2624
In contrast to short helical peptides, constrained peptides, and foldamers, the design and fabrication of crystalline 3D frameworks from the β-sheet peptides are rare because of their high self-aggregation propensity to form 1D architectures. Herein, we demonstrate the formation of a 3D porous honeycomb framework through the silver coordination of a minimal β-sheet forming a peptide having terminal metal coordinated 4- and 3-pyridyl ligands.
Shioukhi I., Batchu H., Schwartz G., Minion L., Deree Y., Bogoslavsky B., Shimon L. J., Wade J., Hoffman R., Fuchter M. J., Markovich G. & Gidron O. (2024) Angewandte Chemie - International Edition. 63, 11, e202319318
Helicity is expressed differently in ortho- and para-fused aceneshelicenes and twistacenes, respectively. While the extent of helicity is constant in helicenes, it can be tuned in twistacenes, and the handedness of flexible twistacenes is often determined by more rigid helicenes. Here, we combine helicenes with rigid twistacenes consisting of a tunable degree of twisting, forming helitwistacenes. While the X-ray structures reveal that the connection does not affect the helicity of each moiety, their electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) spectra are strongly affected by the helicity of the twistacene unit, resulting in solvent-induced sign inversion. ROESY NMR and TD-DFT calculations support this observation, which is explained by differences in the relative orientation of the helicene and twistacene moieties.
Yuan H., Cazade P. A., Zhou S., Shimon L. J., Yuan C., Tan D., Liu C., Fan W., Thangavel V., Cao Y., Thompson D., Yan X., Yang R., Xue B. & Gazit E. (2024) Small. 20, 17, 2309493
Sulfonic acid-containing bioorganic monomers with wide molecular designability and abundant hydrogen bonding sites hold great potential to design diverse functional biocrystals but have so far not been explored for piezoelectric energy harvesting applications due to the lack of strategies to break the centrosymmetry of their assemblies. Here, a significant molecular packing transformation from centrosymmetric into non-centrosymmetric conformation by the addition of an amide terminus in the sulfonic acid-containing bioorganic molecule is demonstrated, allowing a high electromechanical response. The amide-functionalized molecule self-assembles into a polar supramolecular parallel β-sheet-like structure with a high longitudinal piezoelectric coefficient d<sub>11</sub> = 15.9 pm V<sup>−1</sup> that produces the maximal open-circuit voltage of >1 V and the maximal power of 18 nW in nanogenerator devices pioneered. By contrast, molecules containing an amino or a cyclohexyl terminus assemble into highly symmetric 3D hydrogen bonding diamondoid-like networks or 2D double layer structures that show tunable morphologies, thermostability, and mechanical properties but non-piezoelectricity. This work not only presents a facile approach to achieving symmetry transformation of bioorganic assemblies but also demonstrates the terminal group and the property correlation for tailor-made design of high-performance piezoelectric biomaterials.
Lavi Y., Montag M., Diskin-Posner Y., Avram L., Shimon L. J., Ben-David Y. & Milstein D. (2024) Inorganica Chimica Acta. 559, 121787
Acridine-based PNP-type pincer ligands (AcrPNP) have previously been used for the construction of a small number of Ru(II), Mn(I), Rh(III) and Ir(III) complexes, with most attention being given to the catalytically-active ruthenium complexes. In the present work, we significantly expand the scope of known AcrPNP complexes by introducing a series of new Ir(I) and Ir(III) complexes. These were synthesized from two AcrPNP ligands differing in their P-substituents (<sup>i</sup>Pr vs Ph), in conjunction with various Ir(I)-olefin precursors, through different sequences of reactions that include intramolecular C[sbnd]H activations and additions of H<sub>2</sub> and NaBEt<sub>3</sub>H. The new iridium complexes, with their observed structures and reactivities, reflect the unique properties of the acridine-based PNP ligands, i.e., their inherent structural flexibility and ability to support both metal-centered reactivity (C[sbnd]H and H[sbnd]H oxidative addition) and ligand-centered reactivity (hydride- and H<sub>2</sub>-induced dearomatization).
Lee L. M., Tirukoti N. D., Subramani B., Goren E., Diskin-Posner Y., Allouche-Arnon H. & Bar-Shir A. (2024) ACS Sensors. 9, 11, p. 5770-5775
The rapid fluctuations of metal ion levels in biological systems are faster than the time needed to map fluorinated sensors designed for the <sup>19</sup>F-MRI of cations. An attractive modular solution might come from the activity-based sensing approach. Here, we propose a highly reactive but still ultimately specific synthetic fluorinated sensor for <sup>19</sup>F-MRI mapping of labile Zn<sup>2+</sup>. The sensor comprises a dipicolylamine scaffold for Zn<sup>2+</sup> recognition conjugated to a fluorophenyl acetate entity. Upon binding to Zn<sup>2+</sup>, the synthetic sensor is readily hydrolyzed, and the frequency of its <sup>19</sup>F-functional group in <sup>19</sup>F-NMR is shifted by 12 ppm, allowing the display of the Zn<sup>2+</sup> distribution as an artificial MRI-colored map highlighting its specificity compared to other metal ions. The irreversible Zn<sup>2+</sup>-induced hydrolysis results in a \u201cturn-on\u201d <sup>19</sup>F-MRI, potentially detecting the cation even upon a transient elevation of its levels. We envision that additional metal-ion sensors can be developed based on the principles demonstrated in this work, expanding the molecular toolbox currently used for <sup>19</sup>F-MRI.
Lu L., Luo J., Montag M., Diskin-Posner Y. & Milstein D. (2024) Journal of the American Chemical Society. 146, 31, p. 22017-22026
Polyoxymethylene (POM) is a commonly used engineering thermoplastic, but its recycling by conventional means, i.e., mechanical recycling, is not practiced to any meaningful extent, due to technical limitations. Instead, waste POM is typically incinerated or disposed in landfills, where it becomes a persistent environmental pollutant. An attractive alternative to mechanical recycling is upcycling, namely, the conversion of waste POM into value-added chemicals, but this has received very little attention. Herein, we report the upcycling of POM into useful chemicals through three different reactions, all of which are efficiently catalyzed by a single pincer complex of earth-abundant manganese. One method involves hydrogenation of POM into methanol using H<sub>2</sub> gas as the only reagent, whereas another method converts POM into methanol and CO<sub>2</sub> through a one-pot process comprising acidolysis followed by Mn-catalyzed disproportionation. The third method utilizes POM as a reagent for the methylation of ketones and amines.
Farber M., Rawat V., Diskin-Posner Y., Dobrovetsky R. & Vigalok A. (2024) Organic Letters. 26, 27, p. 5731-5735
Calixpyrenes, calix[4]arenes incorporating one or two pyrene moieties as a part of their hydrophobic cavities, have been prepared and fully characterized. Distally di-O-propoxy diether of the calix dipyrene, which exists in the pinched cone conformation with nearly parallel pyrene moieties, demonstrates strongly enhanced binding of an organic cation (N-methylpyridinium) compared with the analogous diethers of the parent calix[4]arene.
Liang Y., Efremenko I., Diskin-Posner Y., Avram L. & Milstein D. (2024) Angewandte Chemie - International Edition. 63, 21, e202401702
Bond activation and catalysis using s-block metals are of great significance. Herein, a series of calcium pincer complexes with deprotonated side arms have been prepared using pyridine-based PNP and PNN ligands. The complexes were characterized by NMR and X-ray crystal diffraction. Utilizing the obtained calcium complexes, unprecedented N<sub>2</sub>O activation by metal-ligand cooperation (MLC) involving dearomatization-aromatization of the pyridine ligand was achieved, generating aromatized calcium diazotate complexes as products. Additionally, the dearomatized calcium complexes were able to activate the N−H bond as well as reversibly activate H<sub>2</sub>, offering an opportunity for the catalytic hydrogenation of various unsaturated molecules. DFT calculations were applied to analyze the electronic structures of the synthesized complexes and explore possible reaction mechanisms. This study is an important complement to the area of MLC and main-group metal chemistry.
Thiyagarajan S., Diskin-Posner Y., Montag M. & Milstein D. (2024) Chemical Science. 15, 7, p. 2571-2577
The coupling of mononitriles into dinitriles is a desirable strategy, given the prevalence of nitrile compounds and the synthetic and industrial utility of dinitriles. Herein, we present an atom-economical approach for the heteroaddition of saturated nitriles to α,β- and β,γ-unsaturated mononitriles to generate glutaronitrile derivatives using a catalyst based on earth-abundant manganese. A broad range of such saturated and unsaturated nitriles were found to undergo facile heteroaddition with excellent functional group tolerance, in a reaction that proceeds under mild and base-free conditions using low catalyst loading. Mechanistic studies showed that this unique transformation takes place through a template-type pathway involving an enamido complex intermediate, which is generated by addition of a saturated nitrile to the catalyst, and acts as a nucleophile for Michael addition to unsaturated nitriles. This work represents a new application of template catalysis for CC bond formation.
Singh V., Feldman Y., Leitus G., Brumfeld V., Shimon L. J., Lahav M. & van der Boom M. E. (2023) Chemistry - A European Journal. 29, 54, e202301825
We demonstrate here how nitrate salts of bivalent copper, nickel, cobalt, and manganese, along with an achiral organic ligand, assemble into various structures such as symmetrical double-decker flowers, smooth elongated hexagonal bipyramids, and hexagonal prisms. Large morphological changes occur in these structures because of different metal cations, although they maintain isomorphous hexagonal crystallographic structures. Metal cations with stronger coordination to ligands (Cu and Ni) tend to form uniform crystals with unusual shapes, whereas weaker coordinating metal cations (Mn and Co) produce crystals with more regular hexagonal morphologies. The unusual flower-like crystals formed with copper nitrate have two pairs of six symmetrical petals with hexagonal convex centers. The texture of the petals indicates dendritic growth. Two different types of morphologies were formed by using different copper nitrate-to-ligand ratios. An excess of the metal salt results in uniform and hexagonal crystals having a narrow size distribution, whereas the use of an excess of ligand results in double-decker morphologies. Mechanistically, an intermediate structure was observed with slightly concave facets and a domed center. Such structures most likely play a key role in the formation of double-decker crystals that can be formed by fusion processes. The coordination chemistry results in isostructural chiral frameworks consisting of two types of continuous helical channels. Four pyridine units from four separate ligands are coordinated to the metal center in a plane having a chiral (propeller-type) arrangement. The individual double-decker flower crystals are homochiral and a batch consists of crystals having both handedness.
Tiwari O. S., Aizen R., Meli M., Colombo G., Shimon L. J. W., Tal N. & Gazit E. (2023) ACS Nano. 17, 4, p. 3506-3517
Molecular self- and co-assembly allow the formation of diverse and well-defined supramolecular structures with notable physical properties. Among the associating molecules, amino acids are especially attractive due to their inherent biocompatibility and simplicity. The biologically active enantiomer of l-histidine (l-His) plays structural and functional roles in proteins but does not self-assemble to form discrete nanostructures. In order to expand the structural space to include l-His-containing materials, we explored the co-assembly of l-His with all aromatic amino acids, including phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), all in both enantiomeric forms. In contrast to pristine l-His, the combination of this building block with all aromatic amino acids resulted in distinct morphologies including fibers, rods, and flake-like structures. Electrospray ionization mass spectrometry (ESI-MS) indicated the formation of supramolecular co-assemblies in all six combinations, but time-of-flight secondary-ion mass spectrometry (ToF-SIMS) indicated the best seamless co-assembly occurs between l-His and l-Phe while in the other cases, different degrees of phase separation could be observed. Indeed, isothermal titration calorimetry (ITC) suggested the highest affinity between l-His and l-Phe where the formation of co-assembled structures was driven by entropy. In accordance, among all the combinations, the co-assembly of l-His and l-Phe produced single crystals. The structure revealed the formation of a 3D network with nanocavities stabilized by hydrogen bonding between -N (l-His) and -NH (l-Phe). Taken together, using the co-assembly approach we expanded the field of amino acid nanomaterials and showed the ability to obtain discrete supramolecular nanostructures containing l-His based on its specific interactions with l-Phe.
Wen Q., Malik N., Addadi Y., Weißenfels M., Singh V., Shimon L. J. W., Lahav M. & van der Boom M. E. (2023) Angewandte Chemie - International Edition. 62, 4, e202214041
In this study, the precise positioning and alignment of arrays of two different guest molecules in a crystalline host matrix has been engineered and resulted in new optically active materials. Sub-nm differences in the diameters of two types of 1D channels are sufficient for size-selective inclusion of dyes. Energy transport occurs between the arrays of different dyes that are included in parallel-positioned nanochannels by Förster resonance energy transfer (FRET). The color of individual micro-sized crystals are dependent on their relative position under polarized light. This angular-dependent behavior is a result of the geometrically constrained orientation of the dyes by the crystallographic packing of the host matrix and is concentration dependent.
Hema K., Grommet A. B., Białek M. J., Wang J., Schneider L., Drechsler C., Yanshyna O., Diskin-Posner Y., Clever G. H. & Klajn R. (2023) Journal of the American Chemical Society.
The architecture of self-assembled host molecules can profoundly affect the properties of the encapsulated guests. For example, a rigid cage with small windows can efficiently protect its contents from the environment; in contrast, tube-shaped, flexible hosts with large openings and an easily accessible cavity are ideally suited for catalysis. Here, we report a \u201cJanus\u201d nature of a Pd<sub>6</sub>L<sub>4</sub> coordination host previously reported to exist exclusively as a tube isomer (T). We show that upon encapsulating various tetrahedrally shaped guests, T can reconfigure into a cage-shaped host (C) in quantitative yield. Extracting the guest affords empty C, which is metastable and spontaneously relaxes to T, and the T⇄C interconversion can be repeated for multiple cycles. Reversible toggling between two vastly different isomers paves the way toward controlling functional properties of coordination hosts \u201con demand\u201d.
Goren E., Iron M. A., Diskin-Posner Y., Falkovich A., Avram L. & Bar-Shir A. (2023) Chemical Science. 14, 41, p. 11351-11358
Metal-capped molecular hosts are unique in supramolecular chemistry, benefitting from the inner cavity's hydrophobic nature and the metal center's electrochemical properties. It is shown here that the paramagnetic properties of the metals in lanthanide-capped cyclodextrins (Ln-α-CDs and Ln-β-CDs) are a convenient NMR indicator for different populations of host-guest complexes in a given solution. The paramagnetic guest exchange saturation transfer (paraGEST) method was used to study the exchange dynamics in systems composed of Ln-α-CDs or Ln-β-CDs with fluorinated guests, revealing multiple co-existing populations of host-guest complexes exclusively in solutions containing Ln-β-CDs. The enhanced spectral resolution of paraGEST, achieved by a strong pseudo contact shift induction, revealed that different molecular guests can adopt multiple orientations within Ln-β-CDs' cavities and, in contrast, only a single orientation inside Ln-α-CDs. Thus, paraGEST, which can significantly improve NMR detectability and spectral resolution of host-guest systems that experience fast exchange dynamics, is a convenient tool for studying supramolecular systems of metal-capped molecular hosts.
Oded B. E., Diskin-Posner Y., Marks V., Kornweitz H. & Grynszpan F. (2023) European Journal of Organic Chemistry. 26, 39, e202300697
Theoretical and experimental mixed approaches are complementary and valuable. Our DFT calculations support the mechanism suggested by Kosower, adding to it a key diaziridine intermediate that determines the relative product distribution of this reaction. Our results are consistent with the formation of the diazoketene intermediate as the rate-limiting step. Based on curve fittings, first or second-order kinetics cannot be ruled out. This may indicate that more than one mechanism is simultaneously at play in this transformation. This unexpected outcome led us to study an alternative cyclopropenone intermediate. Although cyclopropenone is not likely to be formed under thermal conditions, adding it to the reaction mixture results in bimane structures. The most staggering finding from this investigation was the unanticipated generation of the unsymmetrical anti-(Me,Me)(Ph,Ph)bimane. The optimization of this route towards unsymmetrical bimanes will require additional investigation.
Gemen J., Church J. R., Ruoko T. P., Durandin N., Białek M. J., Weißenfels M., Feller M., Kazes M., Odaybat M., Borin V. A., Kalepu R., Diskin-Posner Y., Oron D., Fuchter M. J., Priimagi A., Schapiro I. & Klajn R. (2023) Science (New York, N.Y.). 381, 6664, p. 1357-1363, adh9059
Photoisomerization of azobenzenes from their stable E isomer to the metastable Z state is the basis of numerous applications of these molecules. However, this reaction typically requires ultraviolet light, which limits applicability. In this study, we introduce disequilibration by sensitization under confinement (DESC), a supramolecular approach to induce the E-to-Z isomerization by using light of a desired color, including red. DESC relies on a combination of a macrocyclic host and a photosensitizer, which act together to selectively bind and sensitize E-azobenzenes for isomerization. The Z isomer lacks strong affinity for and is expelled from the host, which can then convert additional E-azobenzenes to the Z state. In this way, the host-photosensitizer complex converts photon energy into chemical energy in the form of out-of-equilibrium photostationary states, including ones that cannot be accessed through direct photoexcitation.
Das P. J., Roy A., Nandi A., Neogi I., Diskin-Posner Y., Marks V., Pinkas I., Amer S., Kozuch S., Firer M., Montag M. & Grynszpan F. (2023) Journal of Organic Chemistry. 88, 19, p. 13475-13489
Dioxobimanes, colloquially known as bimanes, are a well-established family of N-heterobicyclic compounds that share a characteristic core structure, 1,5-diazabicyclo[3.3.0]octadienedione, bearing two endocyclic carbonyl groups. By sequentially thionating these carbonyls in the syn and anti isomers of the known (Me,Me)dioxobimane, we were able to synthesize a series of thioxobimanes, representing the first heavy-chalcogenide bimane variants. These new compounds were extensively characterized spectroscopically and crystallographically, and their aromaticity was probed computationally. Their potential role as ligands for transition metals was demonstrated by synthesizing a representative gold(I)-thioxobimane complex.
Liang Y., Luo J., Diskin-Posner Y. & Milstein D. (2023) Journal of the American Chemical Society. 145, 16, p. 9164-9175
Utilization of main-group metals as alternatives to transition metals in homogeneous catalysis has become a hot research area in recent years. However, their application in catalytic hydrogenation is less common due to the difficulty in heterolytic cleavage of the HH bond. Employing aromatization/de-aromatization metalligand cooperation (MLC) highly enhances the H2 activation process, offering an efficient approach for the hydrogenation of unsaturated molecules catalyzed by main-group metals. Herein, we report a series of new magnesium pincer complexes prepared using PNNH-type pincer ligands. The complexes were characterized by NMR and X-ray single-crystal diffraction. Reversible activation of H2 and NH bonds by MLC employing these pincer complexes was developed. Using the new magnesium complexes, homogeneously catalyzed hydrogenation of aldimines and ketimines was achieved, affording secondary amines in excellent yields. Control experiments and DFT studies reveal that a pathway involving MLC is favorable for the hydrogenation reactions. Moreover, the efficient catalysis was extended to the selective hydrogenation of quinolines and other N-heteroarenes, presenting the first example of hydrogenation of N-heteroarenes homogeneously catalyzed by early main-group metal complexes. This study provides a new strategy for hydrogenation of C═N bonds catalyzed by magnesium compounds and enriches the research of main-group metal catalysis.
Reuveni G., Diskin-Posner Y., Gehrmann C., Godse S., Gkikas G. G., Buchine I., Aharon S., Korobko R., Stoumpos C. C., Egger D. A. & Yaffe O. (2023) Journal of Physical Chemistry Letters. 14, 5, p. 1288-1293
We show that formamidinium-based crystals are distinct from methylammonium-based halide perovskite crystals because their inorganic sublattice exhibits intrinsic local static disorder that coexists with a well-defined average crystal structure. Our study combines terahertz-range Raman scattering with single-crystal X-ray diffraction and first-principles calculations to probe the evolution of inorganic sublattice dynamics with temperature in the range of 10300 K. The temperature evolution of the Raman spectra shows that low-temperature, local static disorder strongly affects the crystal structural dynamics and phase transitions at higher temperatures.
Misra R., Netti F., Koren G., Dan Y., Chakraborty P., Cohen S. R., Shimon L. J. W., Beck R. & Adler-Abramovich L. (2022) Polymer Chemistry. 335, 12
Peptide amphiphiles exhibit excellent self-assembly properties and have potential applications ranging from materials science to nanobiotechnology. Yet, a detailed understanding of supramolecular assembly from an atomistic perspective is still lacking. Here, we demonstrate the spontaneous self-association of an aromatic amphiphilic alpha,beta-hybrid into a hierarchically-oriented crystalline supramolecular polymer under aqueous conditions. Single-crystal analysis after fiber recrystallization revealed that the peptide formed a beta-sheet structure stabilized by intermolecular hydrogen bonds and aromatic-aromatic interactions. The head-to-head salt bridge interaction between the opposite charges and hydrogen bonding between the strands account for the elongated shape of the crystal and for the high mechanical strength of the fibers. A new composite biocompatible hydrogel was further fabricated by co-assembly of the hybrid peptide with a well-established hydrogelator. These findings shed light on molecular-level understanding of the supramolecular assembly of hybrid peptide amphiphiles, facilitating development of new composite hydrogels for various applications.
di Gregorio M. C., Singh V., Shimon L. J. W., Lahav M. & van der Boom M. E. (2022) Journal of the American Chemical Society. 144, 50, p. 22838-22843
The symmetry of a crystal's morphology usually reflects the symmetry of the crystallographic packing. For single crystals, the space and point groups allow only a limited number of mathematical descriptions of the morphology (forms), all of which are convex polyhedrons. In contrast, concave polyhedrons are a hallmark of twinning and polycrystallinity and are typically inconsistent with single crystallinity. Here we report a new type of structure: a concave polyhedron shape single crystal having a multidomain appearance and a rare space group (P622). Despite these unusual structural features, the hexagonal symmetry is revealed at the morphological levels.
Ji W., Xue B., Yin Y., Guerin S., Wang Y., Zhang L., Cheng Y., Shimon L. J. W., Chen Y., Thompson D., Yang R., Cao Y., Wang W., Cai K. & Gazit E. (2022) Journal of the American Chemical Society. 144, 40, p. 18375-18386
Supramolecular packing dictates the physical properties of bio-inspired molecular assemblies in the solid state. Yet, modulating the stacking modes of bio-inspired supramolecular assemblies remains a challenge and the structure-property relationship is still not fully understood, which hampers the rational design of molecular structures to fabricate materials with desired properties. Herein, we present a co-assembly strategy to modulate the supramolecular packing of N-terminally capped alanine-based assemblies (Ac-Ala) by changing the amino acid chirality and mixing with a nonchiral bipyridine derivative (BPA). The co-assembly induced distinct solid-state stacking modes determined by X-ray crystallography, resulting in significantly enhanced electromechanical properties of the assembly architectures. The highest rigidity was observed after the co-assembly of racemic Ac-Ala with a bipyridine coformer (BPA/Ac-DL-Ala), which exhibited a measured Young's modulus of 38.8 GPa. Notably, BPA crystallizes in a centrosymmetric space group, a condition that is broken when co-crystallized with Ac-L-Ala and Ac-D-Ala to induce a piezoelectric response. Enantiopure co-assemblies of BPA/Ac-D-Ala and BPA/Ac-L-Ala showed density functional theory-predicted piezoelectric responses that are remarkably higher than the other assemblies due to the increased polarization of their supramolecular packing. This is the first report of a centrosymmetric-crystallizing coformer which increases the single-crystal piezoelectric response of an electrically active bio-inspired molecular assembly. The design rules that emerge from this investigation of chemically complex co-assemblies can facilitate the molecular design of high-performance functional materials comprised of bio-inspired building blocks.
Misra R., Tang Y., Chen Y., Chakraborty P., Netti F., Vijayakanth T., Shimon L. J. W., Wei G. & AdlerAbramovich L. (2022) Macromolecular Rapid Communications. 43, 19, 2200223
Ordered supramolecular hydrogels assembled by modified aromatic amino acids often exhibit low mechanical rigidity. Aiming to stabilize the hydrogel and understand the impact of conformational freedom and hydrophobicity on the selfassembly process, two building blocks based on 9fluorenylmethoxycarbonylphenylalanine (FmocPhe) gelator which contain two extra methylene units in the backbone, generating FmocγPhe and Fmoc(3hydroxy)γPhe are designed. FmocγPhe spontaneously assembled in aqueous media forming a hydrogel with exceptional mechanical and thermal stability. Moreover, Fmoc(3hydroxy)γPhe, with an extra backbone hydroxyl group decreasing its hydrophobicity while maintaining some molecular flexibility, selfassembled into a transient fibrillar hydrogel, that later formed microcrystalline aggregates through a phase transition. Molecular dynamics simulations and single crystal Xray analyses reveal the mechanism underlying the two residues' distinct selfassembly behaviors. Finally, FmocγPhe and Fmoc(3OH)γPhe coassembly to form a supramolecular hydrogel with notable mechanical properties are demonstrated. It has been believed that the understanding of the structureassembly relationship will enable the design of new functional amino acidbased hydrogels.
Ordered supramolecular hydrogels assembled by modified aromatic amino acids often exhibit low mechanical rigidity. Aiming to stabilize the hydrogel and understand the impact of conformational freedom and hydrophobicity on the selfassembly process, two building blocks containing the minimal FmocγPhenylalanine were designed. Spontaneous assembly in aqueous media allowed the formation of hydrogels with exceptional mechanical and thermal stability.
Gemen J., Białek M. J., Kazes M., Shimon L. J. W., Feller M., Semenov S. N., Diskin-Posner Y., Oron D. & Klajn R. (2022) Chem. 8, 9, p. 2362-2379
Confinement within molecular cages can dramatically modify the physicochemical properties of the encapsulated guest molecules, but such host-guest complexes have mainly been studied in a static context. Combining confinement effects with fast guest exchange kinetics could pave the way toward stimuli-responsive supramolecular systemsand ultimately materialswhose desired properties could be tailored \u201con demand\u201d rapidly and reversibly. Here, we demonstrate rapid guest exchange between inclusion complexes of an open-window coordination cage that can simultaneously accommodate two guest molecules. Working with two types of guests, anthracene derivatives and BODIPY dyes, we show that the former can substantially modify the optical properties of the latter upon noncovalent heterodimer formation. We also studied the light-induced covalent dimerization of encapsulated anthracenes and found large effects of confinement on reaction rates. By coupling the photodimerization with the rapid guest exchange, we developed a new way to modulate fluorescence using external irradiation.
Takebayashi S., Iron M. A., Feller M., Rivada-Wheelaghan O., Leitus G., Diskin-Posner Y., Shimon L. J. W., Avram L., Carmieli R., Wolf S. G., Cohen-Ofri I., Sanguramath R. A., Shenhar R., Eisen M. & Milstein D. (2022) Nature Catalysis. 5, 6, p. 494-502
The olefin metathesis reaction is among the most widely applicable catalytic reactions for carboncarbon double bond formation. Currently, Mo and Rucarbene catalysts are the most common choices for this reaction. It has been suggested that an iron-based catalyst would be a desirable economical and biocompatible substitute of the Ru catalysts; however, practical solutions in this regard are still lacking. Here, we report the discovery and mechanistic studies of three-coordinate iron(II) catalysts for ring-opening metathesis polymerization of olefins. Remarkably, their reactivity enabled the formation of polynorbornene with stereoregularity and high molecular weight (>107gmol1). The polymerization in the presence of styrene revealed cross metathesis reactivity with iron catalysts. Mechanistic studies suggest the possible role of metalligand cooperation in formation of the productive catalyst. This work opens the door to the development of iron complexes that can be economical and biocompatible catalysts for olefin metathesis reactions.
Wen Q., di Gregorio M. C., Shimon L., Pinkas I., Malik N., Kossoy A., Alexandrov E., Proserpio D. M., Lahav M. & van der Boom M. E. (2022) Chemistry - A European Journal. 28, 54, e202201108
We demonstrate the formation of highly interpenetrated frameworks. An interesting observation is the presence of very large adamantane-shaped cages in a single network, making these crystals new entries in the collection of diamondoid-type metal-organic frameworks (MOFs). The frameworks were constructed by assembling tetrahedral pyridine ligands and copper dichloride. Currently, the networks degree of interpenetration is among the highest reported and increases when the size of the ligand is increased. Highly interpenetrated frameworks typically have low surface contact areas. In contrast, in our systems, the voids take up to 63% of the unit cell volume. The frameworks are chiral but formed from achiral components. The chirality is manifested by the coordination chemistry frameworks around the metal center, the structure of the helicoidal channels and the motifs of the individual networks. Channels of both handedness are present within the unit cells. This phenomenon shapes the walls of the channels, which are composed of 10, 16, or 32 chains correlated to the degree of interpenetration 10-, 16- and 32-fold. By changing the distance between the center of the ligand and the coordination moieties, we succeeded in tuning the diameter of the channels. Relatively large channels were formed, having diameters up to 31.0 Å × 14.8 Å.
Misra R., Vijayakanth T., Shimon L. J. W. & Adler-Abramovich L. (2022) Chemical Communications. 58, 44, p. 6445-6448
The occurrence of sequential multiple aromatic residues in a helical sequence is rare compared to the β-sheet rich structure. Here, using helix promoting α-aminoisobutyric acid (Aib) residues, we unravel atomistic details of the helical secondary structure formation and the super helical assembly of two heptapeptides composed of sequential five and six phenylalanine (Phe) residues.
Nasi H., Chiara di Gregorio M., Wen Q., Shimon L. J. W., Kaplan-Ashiri I., Bendikov T., Leitus G., Kazes M., Oron D., Lahav M. & van der Boom M. E. (2022) Angewandte Chemie - International Edition. 61, 34, e202205238
We show that metalorganic frameworks, based on tetrahedral pyridyl ligands, can be used as a morphological and structural template to form a series of isostructural crystals having different metal ions and properties. An iterative crystal-to-crystal conversion has been demonstrated by consecutive cation exchanges. The primary manganese-based crystals are characterized by an uncommon space group (P622). The packing includes chiral channels that can mediate the cation exchange, as indicated by energy-dispersive X-ray spectroscopy on microtome-sectioned crystals. The observed cation exchange is in excellent agreement with the IrvingWilliams series (Mn
Makam P., Yamijala S. S. R. K. C., Bhadram V. S., Shimon L. J. W., Wong B. M. & Gazit E. (2022) Nature Communications. 13, 1, 1505
Enzymes are extremely complex catalytic structures with immense biological and technological importance. Nevertheless, their widespread environmental implementation faces several challenges, including high production costs, low operational stability, and intricate recovery and reusability. Therefore, the de novo design of minimalistic biomolecular nanomaterials that can efficiently mimic the biocatalytic function (bionanozymes) and overcome the limitations of natural enzymes is a critical goal in biomolecular engineering. Here, we report an exceptionally simple yet highly active and robust single amino acid bionanozyme that can catalyze the rapid oxidation of environmentally toxic phenolic contaminates and serves as an ultrasensitive tool to detect biologically important neurotransmitters similar to the laccase enzyme. While inspired by the laccase catalytic site, the substantially simpler copper-coordinated bionanozyme is ∼5400 times more cost-effective, four orders more efficient, and 36 times more sensitive compared to the natural protein. Furthermore, the designed mimic is stable under extreme conditions (pH, ionic strength, temperature, storage time), markedly reusable for several cycles, and displays broad substrate specificity. These findings hold great promise in developing efficient bionanozymes for analytical chemistry, environmental protection, and biotechnology.
Ji W., Yuan H., Xue B., Guerin S., Li H., Zhang L., Liu Y., Shimon L. J. W., Si M., Cao Y., Wang W., Thompson D., Cai K., Yang R. & Gazit E. (2022) Angewandte Chemie - International Edition. 61, 17, e202201234
The physical characteristics of supramolecular assemblies composed of small building blocks are dictated by molecular packing patterns in the solid-state. Yet, the structureproperty correlation is still not fully understood. Herein, we report the unexpected cofacial to herringbone stacking transformation of a small aromatic bipyridine through co-assembly with acetylated glutamic acid. The unique solid-state structural transformation results in enhanced physical properties of the supramolecular organizations. The co-assembly methodology was further expanded to obtain diverse molecular packings by different bipyridine and acetylated amino acid derivatives. This study presents a feasible co-assembly approach to achieve the solid-state stacking transformation of supramolecular organization and opens up new opportunities to further explore the relationship between molecular arrangement and properties of supramolecular assemblies by crystal engineering.
Chakraborty P., Bera S., Mickel P., Paul A., Shimon L. J. W., Arnon Z. A., Segal D., Král P. & Gazit E. (2022) Angewandte Chemie - International Edition. 61, 3, e202113845
Despite the fundamental clinical importance of amyloid fibril formation, its mechanism is still enigmatic. Crystallography of minimal amyloid models was a milestone in the understanding of the architecture and biological activities of amyloid fibers. However, the crystal structure of ultimate dipeptide-based amyloids is not yet reported. Herein, we present the crystal structure of a typical amyloid-forming minimal dipeptide, Ac-Phe-Phe-NH<sub>2</sub> (Ac-FF-NH<sub>2</sub>), showing a canonical β-sheet structure at the atomic level. The simplicity of the structure helped in investigating amyloid-inhibition using crystallography, never previously reported for larger peptide models. Interestingly, in the presence of an inhibitor, the supramolecular packing of Ac-FF-NH<sub>2</sub> molecules rearranged into a supramolecular 2-fold helix (2<sub>1</sub> helix). This study promotes our understanding of the mechanism of amyloid formation and of the structural transitions that occur during the inhibition process in a most fundamental model.
Chen Y., Guerin S., Yuan H., O'Donnell J., Xue B., Cazade P., Haq E. U., Shimon L. J. W., Rencus-Lazar S., Tofail S. A. M., Cao Y., Thompson D., Yang R. & Gazit E. (2022) Journal of the American Chemical Society. 144, 8, p. 3468-3476
The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.
Yanshyna O., Avram L., Shimon L. J. & Klajn R. (2022) Chemical Communications. 58, 21, p. 3461-3464
We show that the optical properties of indigo carmine can be modulated by encapsulation within a coordination cage. Depending on the host/guest molar ratio, the cage can predominantly encapsulate either one or two dye molecules. The 1:1 complex is fluorescent, unique for an indigo dye in an aqueous solution. We have also found that binding two dye molecules stabilizes a previously unknown conformation of the cage.
Neogi I., Darshan V., Linet A., Anjalikrishna P., Sebastian A., Mohanty G., Morimoto A., Suresh C., Yagi S., Posner Y. D., Grynszpan F. & Unni N. (2022) Synthetic Metals. 291, 117185
Inspite of being a good triplet sensitizer, benzophenones are not useful as host materials for phosphorescent organic light-emitting diodes (PhOLEDs), primarily due to their low thermal stability. In this work, we have addressed this shortcoming by judicial tethering of benzoyl units onto different positions of a rigid Trögers base (TB) scaffold to develop two new benzophenone tethered TBs, namely TB-Bz1, and TB-Bz2 as thermally stable host materials for applications in PhOLEDs. The TB-based host molecules were readily synthesized in good yields from the corresponding amines, and were fully characterized using various spectroscopic techniques. These TBs displayed high thermal decomposition temperatures above 320 °C, imparted by the rigid, non-planar, boomerang-shaped scaffold of the Trögers base. It was further observed that the tethering position of the benzoyl units can significantly affect the photophysical properties of the TBs due to the twisting of the benzoyl unit with respect to the TB-core. This assumption was further confirmed by DFT simulations. Taking advantage of the high triplet energy of TBs (>2.8 eV), PhOLED devices were fabricated exploring TBs as the host material and Ir(ppy)3 as the dopant. The maximum external quantum efficiency of 6.1 %, and 6.9 % and maximum luminance of greater than 5000 cd/m2 were obtained using TBs as the host for the proof-of-concept PhOLED devices, where Ir(ppy)3 was employed as the dopant.
Wang J., Avram L., Diskin-Posner Y., Białek M. J., Stawski W., Feller M. & Klajn R. (2022) Journal of the American Chemical Society. 144, 46, p. 21244-21254
Molecular confinement effects can profoundly alter the physicochemical properties of the confined species. A plethora of organic molecules were encapsulated within the cavities of supramolecular hosts, and the impact of the cavity size and polarity was widely investigated. However, the extent to which the properties of the confined guests can be affected by the symmetry of the cagewhich dictates the shape of the cavityremains to be understood. Here we show that cage symmetry has a dramatic effect on the equilibrium between two isomers of the encapsulated spiropyran guests. Working with two Pd-based coordination cages featuring similarly sized but differently shaped hydrophobic cavities, we found a highly selective stabilization of the isomer whose shape matches that of the cavity of the cage. A T<sub>d</sub>-symmetric cage stabilized the spiropyrans' colorless form and rendered them photochemically inert. In contrast, a D<sub>2h</sub>-symmetric cage favored the colored isomer, while maintaining reversible photoswitching between the two states of the encapsulated spiropyrans. We also show that the switching kinetics strongly depend on the substitution pattern on the spiropyran scaffold. This finding was used to fabricate a time-sensitive information storage medium with tunable lifetimes of the encoded messages.
Asher M., Jouclas R., Bardini M., Diskin-Posner Y., Kahn N., Korobko R., Kennedy A. R., Silva de Moraes L., Schweicher G., Liu J., Beljonne D., Geerts Y. & Yaffe O. (2022) ACS Materials Au. 2, 6, p. 699-708
The lattice dynamics of organic semiconductors has a significant role in determining their electronic and mechanical properties. A common technique to control these macroscopic properties is to chemically modify the molecular structure. These modifications are known to change the molecular packing, but their effect on the lattice dynamics is relatively unexplored. Therefore, we investigate how chemical modifications to a core [1]benzothieno[3,2-b]benzothiophene (BTBT) semiconducting crystal affect the evolution of the crystal structural dynamics with temperature. Our study combines temperature-dependent polarization-orientation (PO) low-frequency Raman measurements with first-principles calculations and single-crystal X-ray diffraction measurements. We show that chemical modifications can indeed suppress specific expressions of vibrational anharmonicity in the lattice dynamics. Specifically, we detect in BTBT a gradual change in the PO Raman response with temperature, indicating a unique anharmonic expression. This anharmonic expression is suppressed in all examined chemically modified crystals (ditBu-BTBT and diC8-BTBT, diPh-BTBT, and DNTT). In addition, we observe solidsolid phase transitions in the alkyl-modified BTBTs. Our findings indicate that π-conjugated chemical modifications are the most effective in suppressing these anharmonic effects.
Liang Y., Das U. K., Luo J., Diskin-Posner Y., Avram L. & Milstein D. (2022) Journal of the American Chemical Society. 144, 41, p. 19115-19126
The development of catalysts for environmentally benign organic transformations is a very active area of research. Most of the catalysts reported so far are based on transition-metal complexes. In recent years, examples of catalysis by main-group metal compounds have been reported. Herein, we report a series of magnesium pincer complexes, which were characterized by NMR and X-ray single-crystal diffraction. Reversible activation of H2 via aromatization/dearomatization metal-ligand cooperation was studied. Utilizing the obtained complexes, the unprecedented homogeneous main-group metal catalyzed semihydrogenation of alkynes and hydrogenation of alkenes were demonstrated under base-free conditions, affording Z-alkenes and alkanes as products, respectively, with excellent yields and selectivities. Control experiments and DFT studies reveal the involvement of metal-ligand cooperation in the hydrogenation reactions. This study not only provides a new approach for the semihydrogenation of alkynes and hydrogenation of alkenes catalyzed by magnesium but also offers opportunities for the hydrogenation of other compounds catalyzed by main-group metal complexes.
Mor Markovsky O. E., Ohana T., Borne A., Diskin Posner Y., Asher M., Yaffe O., Shanzer A. & Dayan B. (2022) ACS Photonics. 9, 8, p. 2676-2682
Crystals and fibers doped with rare-earth (RE) ions provide the basis for most of today's solid-state optical systems, from lasers and telecom devices to emerging potential quantum applications such as quantum memories and optical to microwave conversion. The two platforms, doped crystals and doped fibers, seem mutually exclusive, each having its own strengths and limitations, the former providing high homogeneity and coherence and the latter offering the advantages of robust optical waveguides. Here we present a hybrid platform that does not rely on doping but rather on coating the waveguide─a tapered silica optical fiber─with a monolayer of complexes, each containing a single RE ion. The complexes offer an identical, tailored environment to each ion, thus minimizing inhomogeneity and allowing tuning of their properties to the desired application. Specifically, we use highly luminescent Yb3+[Zn(II)MC (QXA)] complexes, which isolate the RE ion from the environment and suppress nonradiative decay channels. We demonstrate that the beneficial optical transitions of the Yb3+ are retained after deposition on the tapered fiber and observe an excited-state lifetime of over 0.9 ms, on par with state-of-the-art Yb-doped inorganic crystals.
Luo J., Liang Y., Montag M., Diskin-Posner Y., Avram L. & Milstein D. (2022) Journal of the American Chemical Society. 144, 29, p. 13266-13275
Catalytic semihydrogenation of internal alkynes using H2 is an attractive atom-economical route to various alkenes, and its stereocontrol has received widespread attention, both in homogeneous and heterogeneous catalyses. Herein, a novel strategy is introduced, whereby a poisoning catalytic thiol is employed as a reversible inhibitor of a ruthenium catalyst, resulting in a controllable H2-based semihydrogenation of internal alkynes. Both (E)- and (Z)-alkenes were obtained efficiently and highly selectively, under very mild conditions, using a single homogeneous acridine-based ruthenium pincer catalyst. Mechanistic studies indicate that the (Z)-alkene is the reaction intermediate leading to the (E)-alkene and that the addition of a catalytic amount of bidentate thiol impedes the Z/E isomerization step by forming stable ruthenium thiol(ate) complexes, while still allowing the main hydrogenation reaction to proceed. Thus, the absence or presence of catalytic thiol controls the stereoselectivity of this alkyne semihydrogenation, affording either the (E)-isomer as the final product or halting the reaction at the (Z)-intermediate. The developed system, which is also applied to the controllable isomerization of a terminal alkene, demonstrates how metal catalysis with switchable selectivity can be achieved by reversible inhibition of the catalyst with a simple auxiliary additive.
Kar S., Luo J., Rauch M., Diskin-Posner Y., Ben-David Y. & Milstein D. (2022) Green chemistry : an international journal and green chemistry resource : GC. 24, 4, p. 1481-1487
We report the dehydrogenative synthesis of esters from enol ethers using water as the formal oxidant, catalyzed by a newly developed ruthenium acridine-based PNP(Ph)-type complex. Mechanistic experiments and density functional theory (DFT)
studies suggest that an inner-sphere stepwise coupled reaction pathway is operational instead of a more intuitive outer-sphere tandem hydrationdehydrogenation pathway.
Bedi A., Manor Armon A., Diskin-Posner Y., Bogosalvsky B. & Gidron O. (2022) Nature Communications. 13, 1, 451
The properties of π-conjugated oligomers and polymers are commonly controlled by side group engineering, main chain engineering, or conformational engineering. The last approach is typically limited to controlling the dihedral angle around the interring single bonds to prevent loss of π-conjugation. Here we propose a different approach to conformational engineering that involves controlling the twist of the aromatic units comprising the backbone by using a tether of varying lengths. We demonstrate this approach by synthesizing an inherently twisted building unit comprised of helically locked tethered acenes, bearing acetylene end-groups to enable backbone extension, which was applied in a series of nine helical oligomers with varying backbone length and twist. We find that the optical and electronic properties of π-conjugated systems may be determined by the additive, antagonistic, or independent effects of backbone length and twist angle. The twisted oligomers display chiral amplification, arising from the formation of secondary helical structures.
Bera S., Dong X., Krishnarjuna B., Raab S. A., Hales D. A., Ji W., Tang Y., Shimon L. J., Ramamoorthy A., Clemmer D. E., Wei G. & Gazit E. (2021) Cell Reports Physical Science. 2, 4, 100391
The understanding and prediction of the solubility of biomolecules, even of the simplest ones, reflect an open question and unmet need. Short aromatic tripeptides are among the most highly aggregative biomolecules. However, in marked contrast, Ala-Phe-Ala (AFA) was surprisingly found to be non-aggregative and could be solubilized at millimolar concentrations. Here, aiming to uncover the underlying molecular basis of its high solubility, we explore in detail the solubility, aggregation propensity, and atomic-level structure of the tripeptide. We demonstrate an unexpectedly high water solubility of AFA reaching 672 mM, two orders of magnitude higher than reported previously. The single crystal structure reveals an anti-parallel β sheet conformation devoid of any aromatic interactions. This study provides clear mechanistic insight into the structural basis of solubility and suggests a simple and feasible tool for its estimation, bearing implications for design of peptide drugs, peptides materials, and advancement of peptide nanotechnology.
Chakraborty P., Bera S., Mickel P., Paul A., Shimon L. J. W., Arnon Z. A., Segal D., Král P. & Gazit E. (2021) Angewandte Chemie. 134, 3, e202113845
Despite the fundamental clinical importance of amyloid fibril formation, its mechanism is still enigmatic. Crystallography of minimal amyloid models was a milestone in the understanding of the architecture and biological activities of amyloid fibers. However, the crystal structure of ultimate dipeptide-based amyloids is not yet reported. Herein, we present the crystal structure of a typical amyloid-forming minimal dipeptide, Ac-Phe-Phe-NH2 (Ac-FF-NH2), showing a canonical β-sheet structure at the atomic level. The simplicity of the structure helped in investigating amyloid-inhibition using crystallography, never previously reported for larger peptide models. Interestingly, in the presence of an inhibitor, the supramolecular packing of Ac-FF-NH2 molecules rearranged into a supramolecular 2-fold helix (21 helix). This study promotes our understanding of the mechanism of amyloid formation and of the structural transitions that occur during the inhibition process in a most fundamental model.
Dishi O., Malakar P., Shimon L. J. W., Ruhman S. & Gidron O. (2021) Chemistry : a European journal. 27, 71, p. 17794-17801
In π-conjugated macrocycles, there is a trade-off between the global and local expression of effects such as aromaticity, with the outcome of the trade-off determined by the geometry and aromaticity of the constituent units. Compared with other aromatic rings, the aromatic character of furan is relatively small, and therefore global effects in macrocyclic furans are expected to be more pronounced. Following our introduction of macrocyclic oligofuran, we present the first synthesis of a series of π-conjugated bifuran macrocycles of various ring sizes, from trimer to hexamer, and characterize them using both computational and experimental methods. The properties of macrocyclic oligofurans change considerably with size: The smaller trimer is rigid, weakly emissive and planar as revealed by its single crystal structure, and displays global antiaromaticity. In contrast, the larger pentamer and hexamer are flexible, emissive, have non-planar structures, and exhibit local aromaticity. The results are supported by NICS and ACID calculations that indicate the global antiaromaticity of planar furan macrocycles, and by transient absorption measurements showing sharp absorption band for the trimer and only the internal conversion decay pathway.
Malik N., Singh V., Shimon L. J. W., Houben L., Lahav M. & van der Boom M. E. (2021) Journal of the American Chemical Society. 143, 41, p. 16913-16918
We demonstrate the formation of both metallo-organic crystals and nanoscale films that have entirely different compositions and structures despite using the same set of starting materials. This difference is the result of an unexpected cation exchange process. The reaction of an iron polypyridyl complex with a copper salt by diffusion of one solution into another resulted in iron-to-copper exchange, concurrent ligand rearrangement, and the formation of metal-organic frameworks (MOFs). This observation shows that polypyridyl complexes can be used as expendable precursors for the growth of MOFs. In contrast, alternative depositions of the iron polypyridyl complex with a copper salt by automated spin coating on conductive metal oxides resulted in the formation of electrochromic coatings, and the structure and redox properties of the iron complex were retained. The possibility to form such different networks from the same set of molecular building blocks by "in solution"versus "on surface"coordination chemistry broadens the synthetic space to design functional materials.
Aviv M., Cohen-Gerassi D., Orr A. A., Misra R., Arnon Z. A., Shimon L. J. W., Shacham-Diamand Y., Tamamis P. & Adler-Abramovich L. (2021) International Journal of Molecular Sciences. 22, 17, 9634
Supramolecular hydrogels formed by the self-assembly of amino-acid based gelators are receiving increasing attention from the fields of biomedicine and material science. Self-assembled systems exhibit well-ordered functional architectures and unique physicochemical properties. However, the control over the kinetics and mechanical properties of the end-products remains puzzling. A minimal alteration of the chemical environment could cause a significant impact. In this context, we report the effects of modifying the position of a single atom on the properties and kinetics of the self-assembly process. A combination of experimental and computational methods, used to investigate double-fluorinated Fmoc-Phe derivatives, Fmoc-3,4F-Phe and Fmoc-3,5F-Phe, reveals the unique effects of modifying the position of a single fluorine on the self-assembly process, and the physical properties of the product. The presence of significant physical and morphological differences between the two derivatives was verified by molecular-dynamics simulations. Analysis of the spontaneous phase-transition of both building blocks, as well as crystal X-ray diffraction to determine the molecular structure of Fmoc-3,4F-Phe, are in good agreement with known changes in the Phe fluorination pattern and highlight the effect of a single atom position on the self-assembly process. These findings prove that fluorination is an effective strategy to influence supramolecular organization on the nanoscale. Moreover, we believe that a deep understanding of the self-assembly process may provide fundamental insights that will facilitate the development of optimal amino-acid-based low-molecular-weight hydrogelators for a wide range of applications.
Chen Y., Yang Y., Orr A. A., Makam P., Redko B., Haimov E., Wang Y., Shimon L. J. W., RencusLazar S., Ju M., Tamamis P., Dong H. & Gazit E. (2021) Angewandte Chemie - International Edition. 60, 31, p. 17164-17170
The structural arrangement of amino acid residues in native enzymes underlies their remarkable catalytic properties, thus providing a notable point of reference for designing potent yet simple biomimetic catalysts. Herein, we describe a minimalistic approach to construct a dipeptide-based nano-superstructure with enzyme-like activity. The self-assembled biocatalyst comprises one peptide as a single building block, readily synthesized from histidine. Through coordination with zinc ion, the peptide self-assembly procedure allows the formation of supramolecular beta-sheet ordered nano-crystals, which can be used as basic units to further construct higher-order superstructure. As a result, remarkable hydrolysis activity and enduring stability are demonstrated. Our work exemplifies the use of a bioinspired supramolecular assembly approach to develop next-generation biocatalysts for biotechnological applications.
Chovnik O., Cohen S. R., Pinkas I., Houben L., Gorelik T. E., Feldman Y., Shimon L. J. W., Iron M. A., Lahav M. & van der Boom M. E. (2021) ACS Nano. 15, 9, p. 14643-14652
We demonstrate the solvent-free amorphous-to-cocrystalline transformations of nanoscale molecular films. Exposing amorphous films to vapors of a haloarene results in the formation of a cocrystalline coating. This transformation proceeds by gradual strengthening of halogen-bonding interactions as a result of the crystallization process. The gassolid diffusion mechanism involves formation of an amorphous metastable phase prior to crystallization of the films. In situ optical microscopy shows mass transport during this process, which is confirmed by cross-section analysis of the final structures using focused ion beam milling combined with scanning electron microscopy. Nanomechanical measurements show that the rigidity of the amorphous films influences the crystallization process. This surface transformation results in molecular arrangements that are not readily obtained through other means. Cocrystals grown in solution crystallize in a monoclinic centrosymmetric space group, whereas the on-surface halogen-bonded assembly crystallizes into a noncentrosymmetric material with a bulk second-order nonlinear optical response.
Singh V., Houben L., Shimon L. J. W., Cohen S. R., Golani O., Feldman Y., Lahav M. & van der Boom M. E. (2021) Angewandte Chemie - International Edition. 60, 33, p. 18256-18264
We demonstrate here a unique metalloorganic material where the appearance and the internal crystal structure are in contradiction. The eggshaped (ovoid) crystals have a brainlike texture. Although these microsized crystals are monodispersed; like fingerprints their grainy surfaces are never exactly alike. Remarkably, our Xray and electron diffraction studies unexpectedly revealed that these structures are singlecrystals comprising a continuous coordination network of two differently shaped homochiral channels. By using the same building blocks under different reaction conditions, a rare series of crystals have been obtained that are uniquely rounded in their shape. In stark contrast to the brainlike crystals, these isostructural and monodispersed crystals have a comparatively smooth appearance. The sizes of these crystals vary by several orders of magnitude.The eggshaped homochiral crystals: A brainlike texture combined with single crystallinity. A series of isomorphous crystals found in a rare space group have been formed with varied morphologies. These crystals contain chiral channels and are made from achiral components.
Bera S., Guerin S., Yuan H., O'Donnell J., Reynolds N. P., Maraba O., Ji W., Shimon L. J. W., Cazade P., Tofail S. A. M., Thompson D., Yang R. & Gazit E. (2021) Nature Communications. 12, 1, 2634
Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d<sub>35</sub> = 27 pm V<sup>−1</sup>). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.
Novichkov A. I., Hanopolskyi A. I., Miao X., Shimon L. J. W., Diskin-Posner Y. & Semenov S. N. (2021) Nature Communications. 12, 1, 2994
Autocatalytic and oscillatory networks of organic reactions are important for designing life-inspired materials and for better understanding the emergence of life on Earth; however, the diversity of the chemistries of these reactions is limited. In this work, we present the thiol-assisted formation of guanidines, which has a mechanism analogous to that of native chemical ligation. Using this reaction, we designed autocatalytic and oscillatory reaction networks that form substituted guanidines from thiouronium salts. The thiouronium salt-based oscillator show good stability of oscillations within a broad range of experimental conditions. By using nitrile-containing starting materials, we constructed an oscillator where the concentration of a bicyclic derivative of dihydropyrimidine oscillates. Moreover, the mixed thioester and thiouronium salt-based oscillator show unique responsiveness to chemical cues. The reactions developed in this work expand our toolbox for designing out-of-equilibrium chemical systems and link autocatalytic and oscillatory chemistry to the synthesis of guanidinium derivatives and the products of their transformations including analogs of nucleobases.
Thenarukandiyil R., Satheesh V., Shimon L. J. W. & de Ruiter G. (2021) Chemistry - An Asian Journal. 16, 8, p. 999-1006
During the past decade earth-abundant metals have become increasingly important in homogeneous catalysis. One of the reactions in which earth-abundant metals have found important applications is the hydroboration of unsaturated C−C and C−X bonds (X=O or N). Within these set of transformations, the hydroboration of challenging substrates such as nitriles, carbonates and esters still remain difficult and often relies on elaborate ligand designs and highly reactive catalysts (e. g., metal alkyls/hydrides). Here we report an effective methodology for the hydroboration of challenging C≡N and C=O bonds that is simple and applicable to a wide set of substrates. The methodology is based on using a manganese(II) triflate salt that, in combination with commercially available potassium tert-butoxide and pinacolborane, catalyzes the hydroboration of nitriles, carbonates, and esters at room temperature and with near quantitative yields in less than three hours. Additional studies demonstrated that other earth-abundant metal triflate salts can facilitate this reaction as well, which is further discussed in this report.
Zou Y. Q., von Wolff N., Rauch M., Feller M., Zhou Q. Q., Anaby A., Diskin-Posner Y., Shimon L. J., Avram L., Ben-David Y. & Milstein D. (2021) Chemistry - A European Journal. 27, 14, p. 4715-4722
Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO<sub>2</sub> emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.
Ji W., Xue B., Bera S., Guerin S., Shimon L. J., Ma Q., Tofail S. A., Thompson D., Cao Y., Wang W. & Gazit E. (2021) Materials Today. 42, p. 29-40
Amino acid chirality plays an important role in conveying directionality and specificity to their supramolecular organization. However, the impact of enantiopure and racemic amino acids on the favorable packing and macroscopic properties of organic cocrystals with nonchiral coformers is poorly understood. Herein, we performed a systematic study of the effect of chirality on the macroscopic properties of acetylated alanine (AcA) single crystals and cocrystals with a nonchiral photo-sensitive bipyridine derivative (BPE). Cocrystallization with BPE produced a marked morphology transition that improved the supramolecular chirality, thermal stability and mechanical strength of AcA crystals. The distinct supramolecular packing modes were analyzed by X-ray crystallography. The highest rigidity was observed for BPE/DL-AcA, while BPE/D-AcA and BPE/L-AcA crystals exhibited higher efficiency of photo-induced emission for fluorescent imprinting, as well as significantly higher piezoelectricity. This work provides a striking illustration that subtle differences in amino acid stereochemistry translate into tunable macroscopic properties of organic cocrystals for future applications in rigid solids, fluorescent imprinting, and energy harvesting.
di Gregorio M. C., Elsousou M., Wen Q., Shimon L. J. W., Brumfeld V., Houben L., Lahav M. & van der Boom M. E. (2021) Nature Communications. 12, 1, 957
The coexistence of single-crystallinity with a multidomain morphology is a paradoxical phenomenon occurring in biomineralization. Translating such feature to synthetic materials is a highly challenging process in crystal engineering. We demonstrate the formation of metallo-organic single-crystals with a unique appearance: six-connected half-rods forming a hexagonal-like tube. These uniform objects are formed from unstable, monodomain crystals. The monodomain crystals dissolve from the inner regions, while material is anisotropically added to their shell, resulting in hollow, single-crystals. Regardless of the different morphologies and growth mechanism, the crystallographic structures of the mono- and multidomain crystals are nearly identical. The chiral crystals are formed from achiral components, and belong to a rare space group (P622). Sonication of the solvents generating radical species is essential for forming the multidomain single-crystals. This process reduces the concentration of the active metal salt. Our approach offers opportunities to generate a new class of crystals.
Degtjarik O., Golovenko D., Diskin-Posner Y., Abrahmsén L., Rozenberg H. & Shakked Z. (2021) Nature Communications. 12, 1, 7057
In response to genotoxic stress, the tumor suppressor p53 acts as a transcription factor by regulating the expression of genes critical for cancer prevention. Mutations in the gene encoding p53 are associated with cancer development. PRIMA-1 and eprenetapopt (APR-246/PRIMA-1
<sup>MET</sup>) are small molecules that are converted into the biologically active compound, methylene quinuclidinone (MQ), shown to reactivate mutant p53 by binding covalently to cysteine residues. Here, we investigate the structural basis of mutant p53 reactivation by MQ based on a series of high-resolution crystal structures of cancer-related and wild-type p53 core domains bound to MQ in their free state and in complexes with their DNA response elements. Our data demonstrate that MQ binds to several cysteine residues located at the surface of the core domain. The structures reveal a large diversity in MQ interaction modes that stabilize p53 and its complexes with DNA, leading to a common global effect that is pertinent to the restoration of non-functional p53 proteins.
Mashiach R., Weissman H., Avram-Biton L., Houben L., Diskin Posner Y., Arunachalam V., Leskes M., Rybtchinski B. & Bar-Shir A. (2021) Nano Letters. 21, 23, p. 9916-9921
Colloidal inorganic nanofluorides have aroused great interest for various applications with their development greatly accelerated thanks to advanced synthetic approaches. Nevertheless, understanding their colloidal evolution and the factors that affect their dispersion could improve the ability to rationally design them. Here, using a multimodal in situ approach that combines DLS, NMR, and cryogenic-TEM, we elucidate the formation dynamics of nanofluorides in water through a transient aggregative phase. Specifically, we demonstrate that ligand-cation interactions mediate a transient aggregation of as-formed CaF2 nanocrystals (NCs) which governs the kinetics of the colloids' evolution. These observations shed light on key stages through which CaF2 NCs are dispersed in water, highlighting fundamental aspects of nanofluorides formation mechanisms. Our findings emphasize the roles of ligands in NCs' synthesis beyond their function as surfactants, including their ability to mediate colloidal evolution by complexing cationic precursors, and should be considered in the design of other types of NCs.
Das U. K., Kar S., Ben-David Y., DiskinPosner Y. & Milstein D. (2021) Advanced Synthesis and Catalysis. 363, 15, p. 3744-3749
We report the first example of homogeneously catalyzed hydrogenation of the N=N bond of azo compounds using a complex of an earth-abundant-metal. The hydrogenation reaction is catalyzed by a manganese pincer complex, proceeds under mild conditions, and yields amines, which makes this methodology a sustainable alternative route for the conversion of azo compounds. A plausible mechanism involving metal-ligand cooperation and hydrazine intermediacy is proposed based on mechanistic studies. (Figure presented.).
Zhou Q., Zou Y., Kar S., Diskin-Posner Y., Ben-David Y. & Milstein D. (2021) ACS Catalysis. 11, p. 10239-10245
A simple and efficient system for the hydration and α-deuteration of nitriles to form amides, α-deuterated nitriles, and α-deuterated amides catalyzed by a single pincer complex of the earth-abundant manganese capable of metalligand cooperation is reported. The reaction is selective and tolerates a wide range of functional groups, giving the corresponding amides in moderate to good yields. Changing the solvent from tert-butanol to toluene and using D2O results in formation of α-deuterated nitriles in high selectivity. Moreover, α-deuterated amides can be obtained in one step directly from nitriles and D2O in THF. Preliminary mechanistic studies suggest the transformations contributing toward activation of the nitriles via a metalligand cooperative pathway, generating the manganese ketimido and enamido pincer complexes as the key intermediates for further transformations.
Tirukoti N. D., Avram L., Haris T., Lerner B., Diskin Posner Y., Allouche-Arnon H. & Bar-Shir A. (2021) Journal of the American Chemical Society. 143, 30, p. 11751-11758
Fast ion-chelate dissociation rates and weak ion-chelate affinities are desired kinetic and thermodynamic features for imaging probes to allow reversible binding and to prevent deviation from basal ionic levels. Nevertheless, such properties often result in poor readouts upon ion binding, frequently result in low ion specificity, and do not allow the detection of a wide range of concentrations. Herein, we show the design, synthesis, characterization, and implementation of a Zn2+-probe developed for MRI that possesses reversible Zn2+-binding properties with a rapid dissociation rate (koff = 845 ± 35 s1) for the detection of a wide range of biologically relevant concentrations. Benefiting from the implementation of chemical exchange saturation transfer (CEST), which is here applied in the 19F-MRI framework in an approach termed ion CEST (iCEST), we demonstrate the ability to map labile Zn2+ with spectrally resolved specificity and with no interference from competitive cations. Relying on fast koff rates for enhanced signal amplification, the use of iCEST allowed the designed fluorinated chelate to experience weak Zn2+-binding affinity (Kd at the mM range), but without compromising high cationic specificity, which is demonstrated here for mapping the distribution of labile Zn2+ in the hippocampal tissue of a live mouse. This strategy for accelerating ion-chelate koff rates for the enhancement of MRI signal amplifications without affecting ion specificity could open new avenues for the design of additional probes for other metal ions beyond zinc.
Semenov S. N., Miao X., Paikar A., Lerner B., Diskin-Posner Y. & Shmul G. (2021) Angewandte Chemie - International Edition. 60, 37, p. 20366-20375
Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo . It is well understood how the selection of specific molecules occurs in reaction networks driven by template-assisted ligation; however how selection could occur in strongly interconnected, nonselective, autocatalytic networks is less clear. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys-Xxx-Gly-SR) 2 form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6-12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single-crystal X-ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model \u201cremoval\u201d reaction. These results indicate that autocatalytic production and competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre-Darwinian stages of molecular evolution.
Kar S., Xie Y., Zhou Q. Q., Diskin-Posner Y., Ben-David Y. & Milstein D. (2021) ACS Catalysis. 11, 12, p. 7383-7393
The current existing methods for the amide bond synthesis via acceptorless dehydrogenative coupling of amines and alcohols all require high reaction temperatures for effective catalysis, typically involving reflux in toluene, limiting their potential practical applications. Herein, we report a system for this reaction that proceeds under mild conditions (reflux in diethyl ether, boiling point 34.6 °C) using ruthenium PNNH complexes. The low-temperature activity stems from the ability of RuPNNH complexes to activate alcohol and hemiaminals at near-ambient temperatures through the assistance of the terminal NH proton. Mechanistic studies reveal the presence of an unexpected aldehyde-bound ruthenium species during the reaction, which is also the catalytic resting state. We further utilize the low-temperature activity to synthesize several simple amide bond-containing commercially available pharmaceutical drugs from the corresponding amines and alcohols via the dehydrogenative coupling method.
Menahem M., Dai Z., Aharon S., Sharma R., Asher M., Diskin-Posner Y., Korobko R., Rappe A. M. & Yaffe O. (2021) ACS Nano. 15, 6, p. 10153-10162
Recent investigations of two-dimensional (2D) hybrid organic-inorganic halide perovskites (HHPs) indicate that their optical and electronic properties are dominated by strong coupling to thermal fluctuations. While the optical properties of 2D-HHPs have been extensively studied, a comprehensive understanding of electron-phonon interactions is limited because little is known about their structural dynamics. This is partially because the unit cells of 2D-HHPs contain many atoms. Therefore, the thermal fluctuations are complex and difficult to elucidate in detail. To overcome this challenge, we use polarization-orientation Raman spectroscopy and ab initio calculations to compare the structural dynamics of the prototypical 2D-HHPs [(BA)2PbI4 and (PhE)2PbI4] to their three-dimensional (3D) counterpart, MAPbI3. Comparison to the simpler, 3D MAPbI3 crystal shows clear similarities with the structural dynamics of (BA)2PbI4 and (PhE)2PbI4 across a wide temperature range. The analogy between the 3D and 2D crystals allows us to isolate the effect of the organic cation on the structural dynamics of the inorganic scaffold of the 2D-HHPs. Furthermore, using this approach, we uncover the mechanism of the order-disorder phase transition of (BA)2PbI4 (274 K) and show that it involves relaxation of octahedral tilting coupled to anharmonic thermal fluctuations. These anharmonic fluctuations are important because they induce charge carrier localization and affect the optoelectronic performance of these materials.
Yadav P., Khoury S., Fridman N., Sharma V. K., Kumar A., Majdoub M., Kumar A., Diskin-Posner Y., Mahammed A. & Gross Z. (2021) Angewandte Chemie - International Edition. 60, 23, p. 12829-12834
Heme-like metal-chelating macrocycles, including expanded and contracted porphyrins, are of everlasting interest as drug candidates for numerous diseases. Still, all reported corrole derivatives (and most other heme analogues) do not fulfill the most basic standards expected for oral drug administration: a combination of low molecular weight and reasonable water solubility. We now disclose a very straightforward synthetic method that relies on surprisingly facile trifluoromethyl hydrolysis for gaining access to a new class of corroles that do satisfy all druglikeness criteria. The relevance is briefly exemplified for the iron corroles by demonstrating the ability to affect their association with plasma proteins and their performance for catalase-like decomposition of hydrogen peroxide.
Bedi A., Shimon L. J., Bogoslavsky B. & Gidron O. (2020) Organic Materials. 2, 4, p. 323-329
Twisting anthracene and higher acenes can alter their optical, magnetic, and electronic properties. To test the effect of twisting on the lower homologue, naphthalene, we synthesized tethered naphthalenophanes bearing alkyl bridges. Both X-ray structure and DFT calculations show that hexyl and butyl bridges induce a 6° and 12° end-to-end twist on the naphthalene unit, respectively. Attempts to increase the twisting further using shorter tethers resulted in an elimination product. Enantiomerically pure naphthalenophanes display strong chiroptical properties, which intensify with increasing twist. Attempts to induce bending, rather than twisting, using the same synthetic methodology, resulted in intermolecular dimerization, yielding macrocyclic naphthalenes. This work highlights the importance of steric hindrance in the synthesis of curved cyclophanes using the bridge formation approach.
Mondal A. K., Brown N., Mishra S., Makam P., Wing D., Gilead S., Wiesenfeld Y., Leitus G., Shimon L. J. W., Carmieli R., Ehre D., Kamieniarz G., Fransson J., Hod O., Kronik L., Gazit E. & Naaman R. (2020) ACS Nano. 14, 12, p. 16624-16633
Room-temperature, long-range (300 nm), chirality-induced spin-selective electron conduction is found in chiral metalorganic Cu(II) phenylalanine crystals, using magnetic conductive-probe atomic force microscopy. These crystals are found to be also weakly ferromagnetic and ferroelectric. Notably, the observed ferromagnetism is thermally activated, so that the crystals are antiferromagnetic at low temperatures and become ferromagnetic above ∼50 K. Electron paramagnetic resonance measurements and density functional theory calculations suggest that these unusual magnetic properties result from indirect exchange interaction of the Cu(II) ions through the chiral lattice.
Gemen J., Ahrens J., Shimon L. J. W. & Klajn R. (2020) Journal of the American Chemical Society. 142, 41, p. 17721-17729
Aggregation of organic molecules can drastically affect their physicochemical properties. For instance, the optical properties of BODIPY dyes are inherently related to the degree of aggregation and the mutual orientation of BODIPY units within these aggregates. Whereas the noncovalent aggregation of various BODIPY dyes has been studied in diverse media, the ill-defined nature of these aggregates has made it difficult to elucidate the structureproperty relationships. Here, we studied the encapsulation of three structurally simple BODIPY derivatives within the hydrophobic cavity of a water-soluble, flexible PdII6L4 coordination cage. The cavity size allowed for the selective encapsulation of two dye molecules, irrespective of the substitution pattern on the BODIPY core. Working with a model, a pentamethyl-substituted derivative, we found that the mutual orientation of two BODIPY units in the cages cavity was remarkably similar to that in the crystalline state of the free dye, allowing us to isolate and characterize the smallest possible noncovalent H-type BODIPY aggregate, namely, an H-dimer. Interestingly, a CF3-substituted BODIPY, known for forming J-type aggregates, was also encapsulated as an H-dimer. Taking advantage of the dynamic nature of encapsulation, we developed a system in which reversible switching between H- and J-aggregates can be induced for multiple cycles simply by addition and subsequent destruction of the cage. We expect that the ability to rapidly and reversibly manipulate the optical properties of supramolecular inclusion complexes in aqueous media will open up avenues for developing detection systems that operate within biological environments.
Tao K., Xue B., Han S., Aizen R., Shimon L. J., Xu Z., Cao Y., Mei D., Wang W. & Gazit E. (2020) ACS applied materials & interfaces. 12, 40, p. 45192-45201
Framework materials have shown promising potential in various biological applications. However, the state-of-the-art components show low biocompatibility or mechanical instability, or cannot integrate both optics and electronics, thus severely limiting their extensive applications in biological systems. Herein, we demonstrate that amide-based bioorganic building blocks, including dipeptides and di-peptide nucleic acids, can self-assemble into hydrogen-bonded suprahelix architectures of controllable handedness, which then form suprahelical frameworks with diverse cavities. Especially, the cavities can be tuned to be hydrophilic or hydrophobic, and the shortest diagonal distance can be modulated from 0.5 nm to 1.8 nm, with the volume proportion in the unit cell changing from 5% to 60%. Furthermore, the hydrogen bonding networks result in high mechanical rigidity and semiconductively optoelectronic properties, which allow the utilization of the suprahelical frameworks as supramolecular scaffolds for artificial photosynthesis. Our findings reveal amide-based suprahelix architectures acting as bioinspired supramolecular frameworks, thus extending the constituents portfolio and increasing the feasibility of using framework materials for biological applications.
Garhwal S., Kaushansky A., Fridman N., Shimon L. J. W. & de Ruiter G. (2020) Journal of the American Chemical Society. 142, 40, p. 17131-17139
Earth-abundant metal pincer complexes have played in important role in homogenous catalysis during the last ten years. Yet, despite intense research efforts, the synthesis of iron PCcarbeneP pincer complexes has so far remained elusive. Here we report the synthesis of the first PCNHCP functionalized iron complex [(PCNHCP)FeCl2] (1), and the re-activity of the corresponding trans-dihydride iron(II) dinitrogen complex [(PCNHCP)Fe(H)2N2)] (2). Complex 2 is stable under atmosphere of N2 and highly active for hydrogen isotope exchange at (hetero)aromatic substrates under mild conditions (50 °C, N2). With benzene-d6 as deuterium source, easily reducible functional groups such as esters and amides are well tolerated, contributing to the overall wide substrate scope (e.g. halides, ethers, amines). DFT studies suggest a complex assisted σ-bond metathesis pathway for C(sp2)H bond activation, which is further discussed in this study.
Ghosh M., Bera S., Schiffmann S., Shimon L. J. W. & Adler-Abramovich L. (2020) ACS Nano. 14, 8, p. 9990-10000
Collagen, the most abundant protein in mammals, possesses notable cohesion and elasticity properties, and efficiently induces tissue regeneration. The Gly-Pro-Hyp canonical tripeptide repeating unit of the collagen super helix, has been well characterized. However, to date, the shortest tripeptide repeat demonstrated to attain a helical conformation, contained 3-10 peptide repeats. Here, taking a minimalistic approach, we studied a single repeating unit of collagen in its protected form, Fmoc-Gly-Pro-Hyp. The peptide formed single crstals displaying left-handed polyproline II super-helical packing, as in the native collagen single strand. The crystalline assemblies also display head-to-tail H-bond interactions, and an aromatic zipper arrangement at the molecular interface. The co-assembly of this tripeptide, with Fmoc-Phe-Phe, a well-studied dipeptide hydrogelator, produced twisted helical fibrils with a polyproline II conformation and improved hydrogel mechanical rigidity. The design of these peptides illustrates the possibility to assemble super-helical nanostructures from minimal collagen-inspired peptides with their potential use as functional motifs to introduce a polyproline II conformation into hybrid hydrogel assemblies.
Ji W., Xue B., Bera S., Guerin S., Liu Y., Yuan H., Li Q., Yuan C., Shimon L. J., Ma Q., Kiely E., Tofail S. A. M., Si M., Yan X., Cao Y., Wang W., Yang R., Thompson D., Li J. & Gazit E. (2020) ACS Nano. 14, 8, p. 10704-10715
Molecular stacking modes, generally classified as H-, J-, and X-aggregation play a key role in determining the optoelectronic properties of organic crystals. However, the control of stacking transformation of a specific molecule is an unmet challenge and a priori prediction of the performance in different stacking modes is extraordinarily difficult to achieve. In particular, the existence of hybrid stacking modes and their combined effect on physicochemical properties of molecular crystals are not fully understood. Herein, unexpected stacking transformation from H- to J- and X- aggregation is observed in the crystal structure of a small heterocyclic molecule, 4,4-bipyridine (4,4-Bpy), upon co-assembly with N-acetyl-L-alanine (AcA), a non-aromatic amino acid derivative. This structural transformation into hybrid stacking mode improves physicochemical properties of the co-crystals, including a large red-shifted emission, enhanced supramolecular chirality, improved thermal stability, and higher mechanical properties. While single crystal of 4,4-Bpy shows good optical waveguiding and piezoelectric properties due to the uniform elongated needles and low symmetry of crystal packing, the significantly lower band gap and resistance of the co-crystal indicates improved conductivity. This study not only demonstrates co-crystallization induced packing transformation between H-, J- and X- aggregations in solid state leading to tunable mechanical and optoelectronic properties, but also will inspire future molecular design of organic functional materials by the co-assembly strategy.
Rauch M., Kar S., Kumar A., Avram L., Shimon L. J. W. & Milstein D. (2020) Journal of the American Chemical Society. 142, 34, p. 14513-14521
A series of PNP zinc pincer complexes capable of bond activation via aromatization/dearomatization metal-ligand cooperation (MLC) were prepared and characterized. Reversible heterolytic N-H and H-H bond activation by MLC is shown, in which hemilability of the phosphorus linkers plays a key role. Utilizing this zinc pincer system, base-free catalytic hydrogenation of imines and ketones is demonstrated. A detailed mechanistic study supported by computation implicates the key role of MLC in facilitating effective catalysis. This approach offers a new strategy for (de)hydrogenation and other catalytic transformations mediated by zinc and other main group metals.
Wen Q., Tenenholtz S., Shimon L. J. W., Bar-Elli O., Beck L., Houben L., Cohen S. R., Feldman Y., Oron D., Lahav M. & van der Boom M. E. (2020) Journal of the American Chemical Society. 142, 33, p. 14210-14221
We demonstrate the formation of uniform and oriented metal-organic frameworks using a combination of anion-effects and surface-chemistry. Subtle but significant morphological changes result from the nature of the coordinative counter-anion of the following metal salts: NiX2 with (X = Br-, Cl-, NO3-, and OAc-). Crystals could be obtained in solution or by template surface growth. The latter resulting in truncated crystals that resemble a half-structure of the solution-grown ones. The oriented surface-bound metal-organic frameworks (sMOFs) are obtained via a one-step solvothermal approach, rather than in a layer-by-layer approach. The MOFs are grown on Si/SiOx substrates modified with an organic monolayer or on glass substrates covered with a transparent conductive oxide (TCO). Regardless of the different morphologies, the crystallographic packing is nearly identical and is not affected by the type of anion, nor by solution versus the surface chemistry. A propeller-type arrangement of the non-chiral ligands around the metal center affords a chiral structure with two geometrically different helical channels in a 2:1 ratio with the same handedness. To demonstrate the accessibility and porosity of the macroscopically-oriented channels, a chromophore (resorufin sodium salt) was successfully embedded into the channels of the crystals by diffusion from solution, resulting in fluorescent crystals. These "colored" crystals displayed polarized emission (red) with a high polarization ratio because of the alignment of these dyes imposed by the crystallographic structure. A second-harmonic generation (SHG) study revealed Kleinman-symmetry forbidden non-linear optical properties. These surface-bound and oriented SHG-active MOFs have the potential for use as single non-linear optical (NLO) devices.
Basavalingappa V., Bera S., Xue B., O'Donnell J., Guerin S., Cazade P., Yuan H., Haq E. u., Silien C., Tao K., Shimon L. J. W., Tofail S. A. M., Thompson D., Kolusheva S., Yang R., Cao Y. & Gazit E. (2020) ACS Nano. 14, 6, p. 7025-7037
Diphenylalanine (FF) represents the simplest peptide building block that self-assembles into ordered nanostructures with interesting physical properties. Among self-assembled peptide structures, FF nanotubes display notable stiffness and piezoelectric parameters (Youngs modulus =19-27 GPa, strain coefficient d33= 18 pC/N). Yet, inorganic alternatives remain the major materials of choice for many applications due to higher stiffness and piezoelectricity. Here, aiming to broaden the applications of the FF motif in materials chemistry, we designed three phenyl-rich dipeptides based on the β,β-diphenyl-Ala-OH (Dip) unit: Dip-Dip, cyclo-Dip-Dip, and tert-butyloxycarbonyl (Boc)-Dip-Dip. The doubled number of aromatic groups per unit, compared to FF, produced a dense aromatic zipper network with dramatically improved Youngs modulus of ~70 GPa which is comparable to aluminium. Piezoelectric strain coefficient d33 of ~73 pC/N of such assembly exceeds that of poled polyvinylidene-fluoride (PVDF) polymers and compares well to that of lead zirconium titanate (PZT) thin films and ribbons. The rationally-designed π-π assemblies show a voltage coefficient of 2-3 Vm/N, an order of magnitude higher than PVDF, improved thermal stability up to 360ºC (~60ºC higher than FF) and useful photoluminescence with wide-range excitation-dependent emission in the visible region. Our data demonstrate that aromatic groups improve the rigidity and piezoelectricity of organic self-assembled materials for numerous applications.
Bera S., Xue B., Rehak P., Jacoby G., Ji W., Shimon L. J. W., Beck R., Kral P., Cao Y. & Gazit E. (2020) ACS Nano. 14, 2, p. 1694-1706
Most natural biomolecules may exist in either of two enantiomeric forms. Although in nature, amino acid biopolymers are characterized by L-type homochirality, incorporation of D-amino acids in the design of self-assembling peptide motifs has been shown to significantly alter enzyme stability, conformation, self-assembly behavior, cytotoxicity, and even therapeutic activity. However, while functional metabolite assemblies are ubiquitous throughout nature and play numerous important roles including physiological, structural, or catalytic functions, the effect of chirality on the self-assembly nature and function of single amino acids is not yet explored. Herein, we investigated the self-assembly mechanism of amyloid-like structure formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan (Trp), both previously found as extremely important for the nucleation and self-assembly of aggregation-prone peptide regions into functional structures. Employing D-enantiomers, we demonstrate the critical role that amino acid chirality plays in their self-assembly process. The kinetics and morphology of pure enantiomers is completely altered upon their coassembly, allowing to fabricate different nanostructures that are mechanically more robust. Using diverse experimental techniques, we reveal the different molecular arrangement and self-assembly mechanism of the DL-racemic mixtures that resulted in the formation of advanced supramolecular materials. This study provides a simple yet sophisticated engineering model for the fabrication of attractive materials with bionanotechnological applications.
Tao K., O'Donnell J., Yuan H., Haq E. U., Guerin S., Shimon L. J. W., Xue B., Silien C., Cao Y., Thompson D., Yang R., Tofail S. A. M. & Gazit E. (2020) Energy & Environmental Science. 13, 1, p. 96-101
Bioinspired assemblies bear massive potential for energy generation and storage. Yet, biological molecules have severe limitations for charge transfer. Here, we report l-tryptophan-d-tryptophan assembling architectures comprising alternating water and peptide layers. The extensive connection of water molecules results in significant dipole-dipole interactions and piezoelectric response that can be further engineered by doping via iodine adsorption or isotope replacement with no change in the chemical composition. This simple system and the new doping strategies supply alternative solutions for enhancing charge transfer in bioinspired supramolecular architectures.
Chen Y., Orr A. A., Tao K., Wang Z., Ruggiero A., Shimon L. J. W., Schnaider L., Goodall A., Rencus-Lazar S., Gilead S., Slutsky I., Tamamis P., Tan Z. & Gazit E. (2020) ACS Nano. 14, 3, p. 2798-2807
Peptide self-assembly has attracted extensive interest in the field of eco-friendly optoelectronics and bioimaging due to its inherent biocompatibility, intrinsic fluorescence, and flexible modulation. However, the practical application of such materials was hindered by the relatively low quantum yield of such assemblies. Here, inspired by the molecular structure of BFPms1, we explored the \u201cself-assembly locking strategy\u201d to design and manipulate the assembly of metal-stabilized cyclic(l-histidine-d-histidine) into peptide material with the high-fluorescence efficiency. We used this bioorganic material as an emissive layer in photo- and electroluminescent prototypes, demonstrating the feasibility of utilizing self-assembling peptides to fabricate a biointegrated microchip that incorporates eco-friendly and tailored optoelectronic properties. We further employed a \u201cself-encapsulation\u201d strategy for constructing an advanced nanocarrier with integrated in situ monitoring. The strategy of the supramolecular capture of functional components exemplifies the use of bioinspired organic chemistry to provide frontiers of smart materials, potentially allowing a better interface between sustainable optoelectronics and biomedical applications.
Daw P., Kumar A., Oren D., Espinosa-Jalapa N. A., Srimani D., Diskin-Posner Y., Leitus G., Shimon L. J. W., Carmieli R., Ben-David Y. & Milstein D. (2020) Organometallics. 39, 2, p. 279-285
Acridine-based PNP pincer complexes have been previously utilized for several environmentally benign catalytic processes. In light of the recent growth in interest in base-metal catalysis, we report here the synthesis of acridine-PNP pincer complexes of Ni, Co, Fe, and Mn. We also report here the noninnocent redox nature of these complexes that results in the dimerization of pincer complexes by forming a C-C bond at the C9 position of the acridine ring.
di Gregorio M. C., Shimon L. J., Brumfeld V., Houben L., Lahav M. & van der Boom M. E. (2020) Nature Communications. 11, 1, 380
Naturally occurring single crystals having a multidomain morphology are a counterintuitive phenonomon: the macroscopic appearance is expected to follow the symmetry of the unit cell. Growing such crystals in the lab is a great challenge, especially from organic molecules. We achieve here uniform metallo-organic crystals that exhibit single crystallinity with apparently distinct domains and chirality. The chirality is present at both the molecular and macroscopic levels, although only achiral elements are used. \u201cYo-yo\u201d-like structures having opposite helical handedness evolve from initially formed seemingly achiral cylinders. This non-polyhedral morphology coexists with a continuous coordination network forming homochiral channels. This work sheds light on the enigmatic aspects of fascinating crystallization processes occurring in biological mineralization. Our findings open up opportunities to generate new porous and hierarchical chiral materials.
Tang S., Rauch M., Montag M., Diskin-Posner Y., Ben-David Y. & Milstein D. (2020) Journal of the American Chemical Society. 142, 49, p. 20875-20882
Selective oxidative deamination has long been considered to be an important but challenging transformation, although it is a common critical process in the metabolism of bioactive amino compounds. Most of the synthetic methods developed so far rely on the use of stoichiometric amounts of strong and toxic oxidants. Here we present a green and efficient method for oxidative deamination, using water as the oxidant, catalyzed by a ruthenium pincer complex. This unprecedented reaction protocol liberates hydrogen gas and avoids the use of sacrificial oxidants. A wide variety of primary amines are selectively transformed to carboxylates or ketones in good to high yields. It is noteworthy that mechanistic experiments and DFT calculations indicate that in addition to serving as the oxidant, water also plays an important role in assisting the hydrogen liberation steps involved in amine dehydrogenation.
Luo J., Rauch M., Avram L., Diskin-Posner Y., Shmul G., Ben-David Y. & Milstein D. (2020) Nature Catalysis. 3, 11, p. 887-892
Thioesters play important roles in chemistry and biology, but their synthesis generally exhibits a poor atom economy and generates copious waste. We report here the dehydrogenative coupling of alcohols and thiols to yield thioesters and evolve H-2. This waste-free reaction is catalysed by an acridine-based ruthenium pincer complex in hexamethyldisiloxane as the optimal solvent without any additives. Various thioesters were formed in good-to-excellent yields using equivalent amounts of alcohols and thiols in excellent selectivity with hydrogen gas as the only by-product. A plausible mechanism, which involves an outer-sphere dehydrogenation process in which the thiol not only serves as a reactant, but also as an assisting ligand, is proposed based on mechanistic studies and the isolation of intermediates. This system provides a facile, efficient and waste-free synthesis of thioesters.
Canton M., Grommet A. B., Pesce L., Gemen J., Li S., Diskin-Posner Y., Credi A., Pavan G. M., Andréasson J. & Klajn R. (2020) Journal of the American Chemical Society. 142, 34, p. 14557-14565
Photochromic molecules undergo reversible isomerization upon irradiation with light at different wavelengths, a process that can alter their physical and chemical properties. For instance, dihydropyrene (DHP) is a deep-colored compound that isomerizes to light-brown cyclophanediene (CPD) upon irradiation with visible light. CPD can then isomerize back to DHP upon irradiation with UV light or thermally in the dark. Conversion between DHP and CPD is thought to proceed via a biradical intermediate; bimolecular events involving this unstable intermediate thus result in rapid decomposition and poor cycling performance. Here, we show that the reversible isomerization of DHP can be stabilized upon confinement within a PdII6L4 coordination cage. By protecting this reactive intermediate using the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product obtainable from traditionally low-yielding organic reactions.
Zou Y., Zhou Q., Diskin-Posner Y., Ben-David Y. & Milstein D. (2020) Chemical Science. 11, 27, p. 7188-7193
A sustainable, new synthesis of oxalamides, by acceptorless dehydrogenative coupling of ethylene glycol with amines, generating H-2, homogeneously catalyzed by a ruthenium pincer complex, is presented. The reverse hydrogenation reaction is also accomplished using the same catalyst. A plausible reaction mechanism is proposed based on stoichiometric reactions, NMR studies, X-ray crystallography as well as observation of plausible intermediates.
Chen Q., Fridman N., Diskin-Posner Y. & Gross Z. (2020) Chemistry-A European Journal. 26, 43, p. 9481-9485
Palladium complexes of corrole and sapphyrin were prepared in high yield and fully characterized. The corrole provides a tetradentate/trianionic square planar coordination sphere for Pd-II, charge balanced by pyridinium. Both one and two Pd(II)ions may be accommodated by the pentapyrrolic skeleton of the sapphyrin, and in each case the macrocycle acts as bidentate/monoanionic ligand and the inner-sphere square planar geometry is completed by allyl anions coordinated in an eta(3)fashion. NMR spectroscopy and X-ray crystallography data analyses uncovered the presence of interesting stereoisomers due to the flexibility of the ally ligands and also the pyrrole ring(s) that is/are not involved in metal binding.
Janes T., Diskin-Posner Y. & Milstein D. (2020) Angewandte Chemie - International Edition. 59, 12, p. 4932-4936
A family of cationic boron complexes was synthesized, using a dianilidopyridine pincer ligand, which imposes in-plane distortion of the geometry at boron towards T-shaped. Reactivity of these cations toward hydride and base was investigated, and the utility of these cations as precursors to a variety of pi-conjugated BN heterocycles was demonstrated. 300 nm irradiation of a deprotonated pincer boron complex triggered a C-N cleavage/C-C formation yielding a dearomatized boryl imine, which has a structure akin to the long-proposed intermediate in the photochemical Hofmann-Martius rearrangement. The photo-rearrangement triggers relief of the distortion imposed by the pincer ligand.
Asher M., Angerer D., Korobko R., Diskin Posner Y., Egger D. A. & Yaffe O. (2020) Advanced Materials. 32, 10, 1908028
The intermolecular lattice vibrations in smallmolecule organic semiconductors have a strong impact on their functional properties. Existing models treat the lattice vibrations within the harmonic approximation. In this work, polarizationorientation (PO) Raman measurements are used to monitor the temperatureevolution of the symmetry of lattice vibrations in anthracene and pentacene single crystals. Combined with firstprinciples calculations, it is shown that at 10 K, the lattice dynamics of the crystals are indeed harmonic. However, as the temperature is increased, specific lattice modes gradually lose their PO dependence and become more liquidlike. This finding is indicative of a dynamic symmetry breaking of the crystal structure and shows clear evidence of the strongly anharmonic nature of these vibrations. Pentacene also shows an apparent phase transition between 80 and 150 K, indicated by a change in the vibrational symmetry of one of the lattice modes. These findings lay the groundwork for accurate predictions of the electronic properties of highmobility organic semiconductors at room temperature.
Cohen N. P., Lo Presti E., Dell'Acqua S., Jantz T., Shimon L. J. W., Levy N., Nassir M., Elbaz L., Casella L. & Fischer B. (2019) Inorganic Chemistry. 58, 14, p. 8995-9003
Recently, we reported on a series of aminomethylene-phosphonate (AMP) analogues, bearing one or two heterocyclic groups on the aminomethylene moiety, as promising Zn(II) chelators. Given the strong Zn(II) binding properties of these compounds, they may find useful applications in metal chelation therapy. With a goal of inhibiting the devastating oxidative damage caused by prion protein in prion diseases, we explored the most promising ligand, {bis[(1H-imidazol-4-yl)methyl]amino}methylphosphonic acid, AMP-(Im)2, 4, as an inhibitor of the oxidative reactivity associated with the Cu(II) complex of prion peptide fragment 84-114. Specifically, we first characterized the Cu(II) complex with AMP-(Im)(2) by ultraviolet visible spectroscopy and electrochemical measurements that indicated the high chemical and electrochemical stability of the complex. Potentiometric pH titration provided evidence of the formation of a stable 1:1 [Cu(II)-AMP-(Im)(2)](+) complex (ML), with successive binding of a second AMP-(Im)(2) molecule yielding ML2 complex [Cu(II)-(AMP-(Im)(2))(2)](+) (log K' = 15.55), and log beta' = 19.84 for ML2 complex. The CuN3O1 ML complex was demonstrated by X-ray crystallography, indicating the thermodynamically stable square pyramidal complex. Chelation of Cu(II) by 4 significantly reduced the oxidation potential of the former. CuCl2 and the 1:2 Cu:AMP-(Im)(2) complex showed one-electron redox of Cu(II)/Cu(I) at 0.13 and -0.35 V, respectively. Indeed, 4 was found to be a potent antioxidant that at a 1:1:1 AMP-(Im)(2):Cu(II)-PrP84-114 molar ratio almost totally inhibited the oxidation reaction of 4-methylcatechol. Circular dichroism data suggest that this antioxidant activity is due to formation of a ternary, redox inactive Cu(II)-Prp(84-114)-[AMP-Im)(2)] complex. Future studies in prion disease animal models are warranted to assess the potential of 4 to inhibit the devastating oxidative damage caused by PrP.Errata: Page 8995. Dr. Bosmat Levi-Hevroni designed, synthesized,
and supplied the major compound investigated in our joint paper. Her name was
originally on the author list but then was omitted by mistake. Unfortunately,
we did not notice this mistake until after the article was published. Her name
has been readded to the list with the approval of all of the authors.
Mondal S., Basavalingappa V., Jacoby G., Shimon L. J. W., Beck R. & Gazit E. (2019) ACS Nano. 13, 11, p. 12630-12637
Coiled-coil peptides represent the principal building blocks for structure-based design of bionanomaterials. The sequence-structure relationship and precise nanoscale ordering of the coiled-coil helices originate from the knob-into-hole (KIH) packing of side chains. The helical interface stabilized by the KIH interaction is known to have chain lengths ranging from 30 to 1000 residues. Yet the shortest peptide required for oligomerization through KIH assembly is still unknown. Here, we report that through atomic resolution a minimal seven-residue amphipathic helix forms a different type of KIH motif, termed "supramolecular KIH packing", which confers an exceptional stability to the helical dimers. Significantly, at a low pH, the peptide self-assembles into nanofibers with coiled-coil architecture resembling the natural fibrous proteins. Furthermore, hierarchical ordering of the nanofibers affords lyotropic liquid crystals composed of a shortest natural helical sequence. Thus, this study expands the sequence space for a coiled-coil folding manifold and provides another paradigm for designer nanomaterials from minimal helical sequences.
Basavalingappa V., Bera S., Xue B., Azuri I., Tang Y., Tao K., Shimon L. J. W., Sawaya M. R., Kolusheva S., Eisenberg D. S., Kronik L., Cao Y., Wei G. & Gazit E. (2019) Nature Communications. 10, 1, 5256
The variety and complexity of DNA-based structures make them attractive candidates for nanotechnology, yet insufficient stability and mechanical rigidity, compared to polyamide-based molecules, limit their application. Here, we combine the advantages of polyamide materials and the structural patterns inspired by nucleic-acids to generate a mechanically rigid fluorenylmethyloxycarbonyl (Fmoc)-guanine peptide nucleic acid (PNA) conjugate with diverse morphology and photoluminescent properties. The assembly possesses a unique atomic structure, with each guanine head of one molecule hydrogen bonded to the Fmoc carbonyl tail of another molecule, generating a non-planar cyclic quartet arrangement. This structure exhibits an average stiffness of 69.6 +/- 6.8 Nm(-1) and Young's modulus of 17.8 +/- 2.5 GPa, higher than any previously reported nucleic acid derived structure. This data suggests that the unique cation-free "basket" formed by the Fmoc-G-PNA conjugate can serve as an attractive component for the design of new materials based on PNA self-assembly for nanotechnology applications.
Makam P., Yamijala S. S. R. K. C., Tao K., Shimon L. J. W., Eisenberg D. S., Sawaya M. R., Wong B. M. & Gazit E. (2019) Nature Catalysis. 2, 11, p. 977-985
Enzymatic activity is crucial for various technological applications, yet the complex structures and limited stability of enzymes often hinder their use. Hence, denovo design of robust biocatalysts that are much simpler than their natural counterparts and possess enhanced catalytic activity has long been a goal in biotechnology. Here, we present evidence for the ability of a single amino acid to self-assemble into a potent and stable catalytic structural entity. Spontaneously, phenylalanine (F) molecules coordinate with zinc ions to form a robust, layered, supramolecular amyloid-like ordered architecture (F-Zn(II)) and exhibit remarkable carbonic anhydrase-like catalytic activity. Notably, amongst the reported artificial biomolecular hydrolases, F-Zn(II) displays the lowest molecular mass and highest catalytic efficiency, in addition to reusability, thermal stability, substrate specificity, stereoselectivity and rapid catalytic CO2 hydration ability. Thus, this report provides a rational path towards future denovo design of minimalistic biocatalysts for biotechnological and industrial applications.
Tao K., Xue B., Li Q., Hu W., Shimon L. J. W., Makam P., Si M., Yan X., Zhang M., Cao Y., Yang R., Li J. & Gazit E. (2019) Materials Today. 30, p. 10-16
Low biocompatibility or engineerability of conventional inorganic materials limits their extensive application for power harvesting in biological systems or at bio-machine interfaces. In contrast, intrinsically biocompatible peptide self-assemblies have shown promising potential as a new type of ideal components for eco-friendly optoelectronic energy-harvesting devices. However, the structural instability, weak mechanical strength, and inefficient optical or electrical properties severely impede their extensive application. Here, we demonstrate tryptophan-based aromatic dipeptide supramolecular structures to be direct wide-gap semiconductors. The molecular packings can be effectively modulated by changing the peptide sequence. The extensive and directional hydrogen bonding and aromatic interactions endow the structures with unique rigidity and thermal stability, as well as a wide-spectrum photoluminescence covering nearly the entire visible region, optical waveguiding, temperature/irradiation-dependent conductivity, and the ability to sustain quite high external electric fields. Furthermore, the assemblies display high piezoelectric properties, with a measured open-circuit voltage of up to 1.4 V. Our work provides insights into using aromatic short peptide self-assemblies for the fabrication of biocompatible, miniaturized electronics for power generation with tailored semiconducting optoelectronic properties and improved structural stability.
Niazov-Elkan A., Sui X., Kaplan-Ashiri I., Shimon L. J. W., Leitus G., Cohen E., Weissman H., Wagner H. D. & Rybtchinski B. (2019) ACS Nano. 13, 10, p. 11097-11106
In view of their facile fabrication and recycling, functional materials that are built from small molecules ("molecular plastics") may represent a cost-efficient and sustainable alternative to conventional covalent materials. We show how molecular plastics can be made robust and how their (nano)structure can be tuned via modular construction. For this purpose, we employed binary composites of organic nanocrystals based on a perylene diimide derivative, with graphene oxide (GO), bentonite nanoclay (NC), or hydroxyethyl cellulose (HEC), that both reinforce and enable tailoring the properties of the membranes. The hybrids are prepared via a simple aqueous deposition method, exhibit enhanced mechanical robustness, and can be recycled. We utilized these properties to create separation membranes with tunable porosity that are easy to fabricate and recycle. Hybrids 1/HEC and 1/NC are capable of ultrafiltration, and 1/NC removes heavy metals from water with high efficiency. Hybrid 1/GO shows mechanical properties akin to covalent materials with just 2-10% (by weight) of GO. This hybrid was used as a membrane for immobilizing β-galactosidase that demonstrated long and stable biocatalytic activity. Our findings demonstrate the utility of modular molecular nanoplastics as robust and sustainable materials that enable efficient tuning of structure and function and are based on self-assembly of readily available inexpensive components.
Sinha W., Mahammed A., Fridman N., Diskin-Posner Y., Shimon L. J. W. & Gross Z. (2019) Chemical Communications. 55, 79, p. 11912-11915
Cobalt and iron complexes of corroles with tyrosine-like proton-transfer-relay moieties in proximity to the metal center have been prepared and fully characterized. The (nitrosyl)iron complex performs very well as an electrocatalyst for the reduction of CO2 to CO.
Kumar A., Daw P., Espinosa-Jalapa N. A., Leitus G., Shimon L. J. W., Ben-David Y. & Milstein D. (2019) Dalton Transactions. 48, 39, p. 14580-14584
We report here the activation of CO2 using two Mn-PNN pincer complexes that can exhibit different modes of metal-ligand cooperation amido/amino mode that involves [1,2]-activation of CO2 and dearomatization/aromatization mode that involves [1,3]-activation of CO2. We also compare their catalytic activity for CO2 hydrogenation.
Mulay S. V., Dishi O., Fang Y., Niazi M. R., Shimon L. J. W., Perepichka D. F. & Gidron O. (2019) Chemical Science. 10, 37, p. 8527-8532
We report the first pi-conjugated macrocyclic system with an oligofuran backbone. The calculated HOMO-LUMO gap is similar to that of the corresponding linear polymer, indicating a remarkable electron delocalization. The X-ray structure reveals a planar conformation, in contrast to the twisted conformation of macrocyclic oligothiophenes. The intermolecular pi-pi stacking distance is extremely small (3.17 angstrom), indicating very strong interactions. The macrocycle forms large pi-aggregates in solution and shows a tendency toward highly ordered multilayer adsorption at the solid-liquid interface. The face-on orientation of molecules explains the higher hole mobility observed in the out-of-plane direction.
Zhang Q., Cohen S. R., Rosenhek-Goldian I., Amgar D., Bar-Elli O., Tsarfati Y., Bendikov T., Shimon L. J. W., Feldman Y., Iron M. A., Weissman H., Levine I., Oron D. & Rybtchinski B. (2019) Journal of Physical Chemistry C. 123, 41, p. 25031-25041
Organic photovoltaics enable cost-efficient, tunable, and flexible platforms for solar energy conversion, yet their performance and stability are still far from optimal. Here, we present a study of photoinduced charge transfer processes between electron donor and acceptor organic nanocrystals as part of a pathfinding effort to develop robust and efficient organic nanocrystalline materials for photovoltaic applications. For this purpose, we utilized nanocrystals of perylenediimides as the electron acceptors and nanocrystalline copper phthalocyanine as the electron donor. Three different configurations of donor-acceptor heterojunctions were prepared. Charge transfer in the heterojunctions was studied with Kelvin probe force microscopy under laser or white light excitation. Moreover, detailed morphology characterizations and time-resolved photoluminescence measurements were conducted to understand the differences in the photovoltaic processes of these organic nanocrystals. Our work demonstrates that excitonic properties can be tuned by controlling the crystal and interface structures in the nanocrystalline heterojunctions, leading to a minimization of photovoltaic losses.
Zhan X., Yadav P., Diskin-Posner Y., Fridman N., Sundararajan M., Ullah Z., Chen Q., Shimon L. J. W., Mahammed A., Churchill D. G., Baik M. & Gross Z. (2019) Dalton Transactions. 48, 32, p. 12279-12286
Tris- and tetrakis-beta-trifluoromethylated gallium (3CF(3)-Ga, 4CF(3)-Ga) and aluminum (3CF(3)-Al, 4CF(3)-Al) corrole systems were synthesized by a facile "one-pot" approach from the respective tri- and tetra-iodo starting compounds using the FSO2CF2CO2Me reagent. The isolated 5,10,15-(tris-pentafluorophenyl)corrole-based compounds set the groundwork for another important beta-substituent study in inorganic photocatalysis. As seen previously, -CF3 group substitution leads to red shifts in both the absorption and emission spectra compared to their unsubstituted counterparts (X. Zhan, et al., Inorg. Chem., 2019, 58, 6184-6198). All CF3-substituted corrole complexes showed strong fluorescence; 3CF(3)-Al possessed the highest fluorescence quantum yield (0.71) among these compounds. The photocatalytic production of bromophenol by way of these photosensitizing complexes was studied demonstrating that tris-trifluoromethylation is an important substitution class, especially when Ga3+ is present (experimental TON value in parentheses): 3CF(3)-Ga (192) > 4CF(3)-Ga (146) > 3CF(3)-Al (130) > 4CF(3)-Al (56) > 1-Ga (43) > 1-Al (18). The catalytic performance (turn-over number, TON) for benzylbromide formation (from toluene) was found to be: 3CF(3)-Ga (225) > 1-Ga (138) > 3CF(3)-Al (130) > 4CF(3)-Ga (126) > 1-Al (95) > 4CF(3)-Al (89); in these trials, benzaldehyde was also detected as a product in which 3CF(3)-Ga outperforms the other compounds (TON = 109). The tetra-CF3-substituted 4CF(3)-Ga and 4CF(3)-Al species exhibit a dramatic formal positive shift of 116 mV and 126 mV per [CF3] group, respectively, compared to the unsubstituted parent species 1-Ga and 1-Al. However, the absorbance values (lambda(abs) = 400 nm) of these corrole complexes (all equally concentrated: 4.0 x 10(-6) M) were 3CF(3)-Al (0.23) > 3CF(3)-Ga (0.22) > 1-Al (0.21) > 1-Ga (0.20) > 4CF(3)-Al (0.19) > 4CF(3)-Ga (0.15), which helps rationalize why 3CF(3)-Ga performs the best among these catalysts. These new photosensitizers were carefully characterized by H-1 and F-19 NMR spectroscopy to help verify the number and position (symmetry) of the CF3 groups; 3CF(3)-Ga and 3I-Al were structurally characterized. Distortions in the corrole macrocycle imposed by the multiple beta-substitution were quantified.
Arnon Z. A., Berger O., Aizen R., Hannes K., Brown N., Shimon L. J. W. & Gazit E. (2019) Small Methods. 3, 11, 1900179
The self-assembly of simple units into well-ordered supramolecular polymeric structures may give rise to a broad range of desirable attributes. In the field of bionanotechnology, there are two main classes commonly used as building blocks for self-assembly-amino acids and nucleobases. While protein, peptide, and amino acid building blocks propose broad chemical versatility, the specific Watson-Crick base pairings of nucleic acids allow rational design and precise control over the assembly process. Specifically, artificially synthesized peptide nucleic acids (PNA), short DNA mimics that have an amide backbone, can present a unique set of properties while preserving the specific base pairing of the nucleic acids. The use of complementary building blocks allows the study of supramolecular polymer coassemblies. Here, the coassembly of two paired di-PNA building blocks provides a new layer of control, as both building blocks are required for the spontaneous assembly to occur. Utilizing a microfluidic system, the growth of the well-ordered structure can be regulated and monitored. The crystal structure of the formed assemblies display Watson-Crick base pairing with similar distances as those found in typical DNA double helices. Moreover, the crystals exhibit intriguing optical properties that may be implemented in various materials science and nanotechnological applications.
Shen K., Diskin-Posner Y., Shimon L. J. W., Leitus G., Carmieli R. & Neumann R. (2019) Dalton Transactions. 48, 19, p. 6396-6407
Commonly, iron(ii) and copper(i) complexes bind dioxygen (O-2) and then activate O-2 through a reductive reaction pathway. There is, however, significant interest in low temperature oxygenation with O-2 without the use of a sacrificial reductant. Here, earth-abundant metal complexes (Fe-II, Co-II, Ni-II and Cu-II) coordinated by two different tetra-dentate mono-carbon bridged bis-phenanthroline ligands, (1,10-Phen)(2)-2,2-CR1R2, where R-1 = n-butyl and R-2 = n-butyl or H were synthesized. The structures all showed the expected metal complexation in the equatorial plane by the bridged bis-phenanthroline ligands. For R-1 = n-butyl; R-2 = H, where the ligand has a tertiary carbon bridging group, fast intramolecular oxygenation occurred at the pseudobenzylic position. Depending on the transition metal the main products formed were oxygen bridged dimers of the metal complexes (Co and Fe) or metal complexes with a carbonyl moiety at the bridging pseudobenzylic position as a result of C-R-1 bond cleavage (Ni and Cu). The different product assemblages are explained by different reaction pathways that are metal specific. For quaternary carbon bridged ligands, R-1 = R-2 = n-butyl, the complexes catalytically activated C-H bonds of cyclohexene under catalytic conditions, showing higher effective turnover numbers at low catalyst loading. The reactivity observed is commensurate with a room temperature autooxidation reaction although the initiation of the free radical reaction is metal specific. In general labelling studies with O-18(2), UV-vis and EPR spectroscopy as well as cyclic voltammetry measurements led to a conclusion that the reaction pathways involved both C-H bond activation and O-2 activation.
Yakir H. R., Shimon L. J. W. & Gidron O. (2019) Helvetica Chimica Acta. 102, 5, 1900027
-Conjugated oligomers and polymers consisting of bifuran units are applied in optoelectronic devices, because bifuran units endow such devices with superior properties compared with their thiophene analogs. However, as is true for most furan oligomers, bifuran oligomers suffer from low photostability, which restricts their application. In this work, we present the synthesis and the photophysical and structural characterization of perfluorinated phenyl bifuran (PFB-2F), which displays high photostability, while maintaining strong fluorescence quantum efficiency in both solution and the solid state. X-Ray crystallography reveals that, unlike its thiophene analog, PFB-2F has a completely planar backbone, with slip-stacked packing and short interplanar distances. PFB-2F crystals display mechanofluorochromic behavior, which renders perfluorophenyl-substituted oligofurans potential candidates for both stable optoelectronic devices and responsive optical materials.
Zhan X., Teplitzky P., Diskin-Posner Y., Sundararajan M., Ullah Z., Chen Q., Shimon L. J. W., Saltsman I., Mahammed A., Kosa M., Baik M., Churchill D. G. & Gross Z. (2019) Inorganic Chemistry. 58, 9, p. 6184-6198
An eight-member series of CF3-substituted difluorophosphorus corroles was prepared for establishing a structure-activity profile of these high-potential photo-sensitizers. It consisted of preparing all four possible isomers of the monosubstituted corrole and complexes with 2-, 3-, 4-, and 5-CF3 groups on the macrocycle's periphery. The synthetic pathway to these CF3-substituted derivatives, beginning with (tpfc)PF2, involves two different initial routes: (i) direct electrophilic CF3 incorporation using FSO2CF2CO2Me and copper iodide, or (ii) bromination to achieve the 2,3,8,17,18-pentabrominated compound using excess bromine in methanol. Crystallographic investigations revealed that distortion of the original planar macrocycle is evident even in the monosubstituted case and that it becomes truly severe for the penta-CF3-substituted derivative 5. There is a shift in redox potentials of about 193 mV per -CF3 group, which decreases to only 120 mV for the fifth one in 5. Differences in the electronic spectra suggest that the Gouterman four orbital model decreases in relevance upon gradual -CF3 substitution, a conclusion that was corroborated by DFT calculations. The very significant energy lowering of the frontier orbitals suggested that photoexcitation should lead to a highly oxidizing photocatalyst. This hypothesis was proven true by finding that the most synthetically accessible CF3-substituted derivative is an excellent catalyst for the photoinduced conversion of bromide to bromine (phenol, toluene, and benzene assay).
Bera S., Mondal S., Xue B., Shimon L. J. W., Cao Y. & Gazit E. (2019) Nature Materials. 18, 5, p. 503-509
The structural versatility, biocompatibility and dynamic range of the mechanical properties of protein materials have been explored in functional biomaterials for a wide array of biotechnology applications. Typically, such materials are made from self-assembled peptides with a predominant beta-sheet structure, a common structural motif in silk and amyloid fibrils. However, collagen, the most abundant protein in mammals, is based on a helical arrangement. Here we show that Pro-Phe-Phe, the most aggregation-prone tripeptide of natural amino acids, assembles into a helical-like sheet that is stabilized by the dry hydrophobic interfaces of Phe residues. This architecture resembles that of the functional PSM alpha 3 amyloid, highlighting the role of dry helical interfaces as a core structural motif in amyloids. Proline replacement by hydroxyproline, a major constituent of collagen, generates minimal helical-like assemblies with enhanced mechanical rigidity. These results establish a framework for designing functional biomaterials based on ultrashort helical protein elements.
Tao K., Hu W., Xue B., Chovan D., Brown N., Shimon L. J. W., Maraba O., Cao Y., Tofail S. A. M., Thompson D., Li J., Yang R. & Gazit E. (2019) Advanced Materials. 31, 12, 1807481
Peptide assemblies are ideal components for eco-friendly optoelectronic energy harvesting devices due to their intrinsic biocompatibility, ease of fabrication, and flexible functionalization. However, to date, their practical applications have been limited due to the difficulty in obtaining stable, high-performance devices. Here, it is shown that the tryptophan-based simplest peptide cyclo-glycine-tryptophan (cyclo-GW) forms mechanically robust (elastic modulus up to 24.0 GPa) and thermally stable up to 370 degrees C monoclinic crystals, due to a supramolecular packing combining dense parallel -sheet hydrogen bonding and herringbone edge-to-face aromatic interactions. The directional and extensive driving forces further confer unique optical properties, including aggregation-induced blue emission and unusual stable photoluminescence. Moreover, the crystals produce a high and sustained open-circuit voltage (1.2 V) due to a high piezoelectric coefficient of 14.1 pC N-1. These findings demonstrate the feasibility of utilizing self-assembling peptides for fabrication of biointegrated microdevices that combine high structural stability, tailored optoelectronics, and significant energy harvesting properties.
Bugnola M., Schreiber R. E., Kaufman Y., Leitus G., Shimon L. J. W. & Neumann R. (2019) European Journal of Inorganic Chemistry. 2019, 3-4, p. 482-485
Polyfluoroxometalates (PFOMs) that have a quasi Wells-Dawson structure and have low valent transition metal substitution at the so-called "belt" position, alpha(1)-[H2F6NaM(H2O)W17O55](q-), can reversibly interchange between dimeric and monomeric structures. The dimers have two unique M-mu O-W bridges between two PFOM units. The dimerization occurs through dehydration and was studied as a function of temperature using the visible spectrum that is sensitive to the wavelength and extinction coefficient of the d-d transition. The calculated thermodynamic parameters of the dimerization reaction were iteratively fitted using a function derived from the equilibrium constant and the Beer-Lambert law. Such reversible dimerization reactions have not been observed for similar alpha(1)-[P2M(H2O)W17O61](q-) structures, thus fluorine atoms in an axial position to the transition metal are apparently critical for dimerization by reducing the bond strength of the transition metal-aqua bond trans to the fluorine atom.
Mondal S., Jacoby G., Sawaya M. R., Arnon Z. A., Adler-Abramovich L., Rehak P., Vukovic L., Shimon L. J. W., Kral P., Beck R. & Gazit E. (2019) Journal of the American Chemical Society. 141, 1, p. 363-369
The ensemble of native, folded state was once considered to represent the global energy minimum of a given protein sequence. More recently, the discovery of the cross-beta amyloid state revealed that deeper energy minima exist, often associated with pathogenic, fibrillar deposits, when the concentration of proteins reaches a critical value. Fortunately, a sizable energy barrier impedes the conversion from native to pathogenic states. However, little is known about the structure of the related transition state. In addition, there are indications of polymorphism in the amyloidogenic process. Here, we report the first evidence of the conversion of metastable cross alpha-helical crystals to thermodynamically stable cross-beta-sheet-like fibrils by a de novo designed heptapeptide. Furthermore, for the first time, we demonstrate at atomic resolution that the flip of a peptide plane from a type I to a type II' turn facilitates transformation to cross-beta structure and assembly of a dry steric zipper. This study establishes the potential of a peptide turn, a common protein secondary structure, to serve as a principal gatekeeper between a native metastable folded state and the amyloid state.
Al Rahal O., Hughes G. E., Williams P. A., Logsdail A. J., Diskin-Posner Y. & Harris K. D. M. (2019) Angewandte Chemie - International Edition. 58, 52, p. 18788-18792
A new polymorph of l-tryptophan was prepared through crystallization from the gas phase, with structure determination carried out directly from powder XRD data augmented by periodic DFT-D calculations. The new polymorph (denoted beta) and the previously reported polymorph (denoted alpha) are both based on alternating hydrophilic and hydrophobic layers, but with substantially different hydrogen-bonding arrangements. The beta polymorph exhibits the energetically favourable l2-l2 hydrogen-bonding arrangement, which is unprecedented for amino acids with aromatic side chains. The specific molecular conformations adopted in the beta polymorph facilitate this hydrogen-bonding scheme while avoiding steric conflict of the side chains.
Bruffaerts J., von Wolff N., Diskin-Posner Y., Ben-David Y. & Milstein D. (2019) Journal of the American Chemical Society. 141, 41, p. 16486-16493
Despite the hazardous nature of isocyanates, they remain key building blocks in bulk and fine chemical synthesis. By surrogating them with less potent and readily available formamide precursors, we herein demonstrate an alternative, mechanistic approach to selectively access a broad range of ureas, carbamates, and heterocycles via ruthenium-based pincer complex catalyzed acceptorless dehydrogenative coupling reactions. The design of these highly atom-efficient procedures was driven by the identification and characterization of the relevant organometallic complexes, uniquely exhibiting the trapping of an isocyanate intermediate. Density functional theory (DFT) calculations further contributed to shed light on the remarkably orchestrated chain of catalytic events, involving metal-ligand cooperation.
Hanopolskyi A., De S., Bialek M. J., Diskin-Posner Y., Avram L., Feller M. & Klajn R. (2019) Beilstein Journal of Organic Chemistry. 15, p. 2398-2407
Arylazopyrazoles represent a new family of molecular photoswitches characterized by a near-quantitative conversion between two states and long thermal half-lives of the metastable state. Here, we investigated the behavior of a model arylazopyrazole in the presence of a self-assembled cage based on Pd-imidazole coordination. Owing to its high water solubility, the cage can solubilize the E isomer of arylazopyrazole, which, by itself, is not soluble in water. NMR spectroscopy and X-ray crystallography have independently demonstrated that each cage can encapsulate two molecules of E-arylazopyrazole. UV-induced switching to the Z isomer was accompanied by the release of one of the two guests from the cage and the formation of a 1:1 cage/Z-arylazopyrazole inclusion complex. DFT calculations suggest that this process involves a dramatic change in the conformation of the cage. Back-isomerization was induced with green light and resulted in the initial 1:2 cage/E-arylazopyrazole complex. This back-isomerization reaction also proceeded in the dark, with a rate significantly higher than in the absence of the cage.
Diskin-Posner Y., Amer S., Roy A., Das P. J., Grynszpan F. & Montag M. (2019) Crystal Growth and Design. 19, 8, p. 4358-4368
Li(I) and Na(I) complexes of the fluorescent dye syn-(Me,Me)bimane were isolated and crystallographically characterized, revealing the bimane as a principal component in diverse coordination topologies, including discrete and polymeric structures. The bimane exhibits multiple functions in these frameworks, acting as a variable-denticity O-donor ligand, pi-stacking unit, and hydrogen bond acceptor. These features highlight a new role for syn-bimanes, not as fluorophores, but as versatile building blocks in metal coordination architectures.
Tang S., von Wolff N., Diskin-Posner Y., Leitus G., Ben-David Y. & Milstein D. (2019) Journal of the American Chemical Society. 141, 18, p. 7554-7561
Metal-ligand cooperation (MLC) by dearomatization/aromatization provides a unique way for bond activation, which has led to the discovery of various acceptorless dehydrogenative coupling reactions. However, most of the studies are based on pincer complexes with a central nitrogen donor. Aiming at exploration of the possibility of MLC by PCP-type pincer complexes, we report herein the synthesis, characterization, structure, and reactivity of pyridine-based PCP-Ru complexes. X-ray structures and DFT calculations indicate a carbenoid character of quaternized pyridine-based PCP-Ru complexes. These complexes undergo dearomatization by direct deprotonation, and the dearomatized complex can react with hydrogen, alcohols, or nitriles to regain aromatization via MLC.
Kumar A., Janes T., Chakraborty S., Daw P., von Wolff N., Carmieli R., Diskin-Posner Y. & Milstein D. (2019) Angewandte Chemie - International Edition. 58, 11, p. 3373-3377
We report a C−C bond-forming reaction between benzyl alcohols and alkynes in the presence of a catalytic amount of KO
<sup>t</sup> Bu to form α-alkylated ketones in which the C=O group is located on the side derived from the alcohol. The reaction proceeds under thermal conditions (125 °C) and produces no waste, making the reaction highly atom efficient, environmentally benign, and sustainable. Based on our mechanistic investigations, we propose that the reaction proceeds through radical pathways.
Das U. K., Ben-David Y., Leitus G., Diskin-Posner Y. & Milstein D. (2019) ACS Catalysis. 9, 1, p. 479-484
Base-metal-catalyzed dehydrogenative cross-coupling of primary alcohols to form cross-esters as major products, liberating hydrogen gas, is reported. The reaction is catalyzed by a pincer complex of earth-abundant manganese in the presence of catalytic base, without any hydrogen acceptor or oxidant. Mechanistic insight indicates that a dearomatized complex is the actual catalyst, and indeed this independently prepared dearomatized complex catalyzes the reaction under neutral conditions.
Adler-abramovich L., Arnon Z. A., Sui X., Azuri I., Cohen H., Hod O., Kronik L., Shimon L. J. W., Wagner H. D. & Gazit E. (2018) . 30
Scanning electron microscopy (SEM) studies of laminated selfassembled Ncapped diphenylalanine crystals are presented by Lihi AdlerAbramovich, Ehud Gazit, and coworkers in article number 1704551. These crystals exhibit wellordered crystal packing and diffraction of subÅngstrom resolution, yet display an exceptionally flexible nature. The combination of strength, toughness, and flexibility can be explained in terms of weak interactions between the rigid crystal layers, which are presented in the SEM image shown.
Schierl C., Niazov-Elkan A., Shimon L. J. W., Feldman Y., Rybtchinski B. & Guldi D. M. (2018) Nanoscale. 10, 43, p. 20147-20154
Upon photoexcitation, self-assembled PDI nanocrystals (S1S0) in the form of rods of 70 nm width and 1 mu m length are subject to a symmetry breaking charge separation (SBCS) as the first step in the singlet fission (SF) sequence. Hereby, the correlated pair of triplet excited states (1)(T1T1) is formed with a quantum yield of 122%. Decoherence and triplet diffusion within the nanocrystals affords a long-lived, uncorrelated pair of triplet excited states (T-1 + T-1) with a quantum yield of 24%.
Samanta D., Gemen J., Chu Z., Diskin-Posner Y., Shimon L. J. W. & Klajn R. (2018) Proceedings Of The National Academy Of Sciences Of The United States Of America-Physical Sciences. 115, 38, p. 9379-9384
Efficient molecular switching in confined spaces is critical for the successful development of artificial molecular machines. However, molecular switching events often entail large structural changes and therefore require conformational freedom, which is typically limited under confinement conditions. Here, we investigated the behavior of azobenzene-the key building block of light-controlled molecular machines-in a confined environment that is flexible and can adapt its shape to that of the bound guest. To this end, we encapsulated several structurally diverse azobenzenes within the cavity of a flexible, water-soluble coordination cage, and investigated their light-responsive behavior. Using UV/Vis absorption spectroscopy and a combination of NMR methods, we showed that each of the encapsulated azobenzenes exhibited distinct switching properties. An azobenzene forming a 1:1 host-guest inclusion complex could be efficiently photoisomerized in a reversible fashion. In contrast, successful switching in inclusion complexes incorporating two azobenzene guests was dependent on the availability of free cages in the system, and it involved reversible trafficking of azobenzene between the cages. In the absence of extra cages, photoswitching was either suppressed or it involved expulsion of azobenzene from the cage and consequently its precipitation from the solution. This finding was utilized to develop an information storage medium in which messages could be written and erased in a reversible fashion using light.
di Gregorio M. C., Ranjan P., Houben L., Shimon L. J. W., Rechav K., Lahav M. & van der Boom M. E. (2018) Journal of the American Chemical Society. 140, 29, p. 9132-9139
In this work, we report the formation of superstructures assembled from organic tubular crystals mediated by metal-coordination chemistry. This template-free process involves the crystallization of molecules into crystals having a rectangular and uniform morphology, which then go on to fuse together into multibranched superstructures. The initially hollow and organic crystals are obtained under solvothermal conditions in the presence of a copper salt, whereas the superstructures are subsequently formed by aging the reaction mixture at room temperature. The mild thermodynamic conditions and the favorable kinetics of this unique self-assembly process allowed us to ex-situ monitor the superstructure formation by electron microscopy, highlighting a pivotal and unusual role for copper ions in their formation and stabilization.
Tsarfati Y., Rosenne S., Weissman H., Shimon L. J. W., Gur D., Palmer B. A. & Rybtchinski B. (2018) ACS Central Science. 4, 8, p. 1031-1036
Organic crystals are of primary importance in pharmaceuticals, functional materials, and biological systems; however, organic crystallization mechanisms are not well-understood. It has been recognized that "nonclassical" organic crystallization from solution involving transient amorphous precursors is ubiquitous. Understanding how these precursors evolve into crystals is a key challenge. Here, we uncover the crystallization mechanisms of two simple aromatic compounds (perylene diimides), employing direct structural imaging by cryogenic electron microscopy. We reveal the continuous evolution of density, morphology, and order during the crystallization of very different amorphous precursors (well-defined aggregates and diffuse dense liquid phase). Crystallization starts from initial densification of the precursors. Subsequent evolution of crystalline order is gradual, involving further densification concurrent with optimization of molecular ordering and morphology. These findings may have implications for the rational design of organic crystals.
Bedi A., Shimon L. J. W. & Gidron O. (2018) Journal of the American Chemical Society. 140, 26, p. 8086-8090
Twisting linear acenes out of planarity affects their electronic and optical properties, and induces chirality. However, it is difficult to isolate the effect of twisting from the substituent effect. Moreover, many twistacenes (twisted acenes) readily racemize in solution. Here, we introduce a series of twistacenes having an anthracene backbone diagonally tethered by an n-alkyl bridge, which induces a twist of various angles. This allows us to systematically monitor the effect of twisting on electronic and optical properties. We find that absorption is bathochromically shifted with increasing twist, while fluorescence quantum efficiency drops dramatically. The tethered twistacenes were isolated to their enantiomerically pure form, displaying strong chiroptical properties and anisotropy factor (g-value). No racemization was observed even upon prolonged heating, rendering these tethered twistacenes suitable as enantiopure helical building units for pi-conjugated backbones.
Keisar H., de Ruiter G., Velders A. H., Milko P., Gulino A., Evmenenko G., Shimon L. J. W., Diskin-Posner Y., Lahav M. & van der Boom M. E. (2018) Journal of the American Chemical Society. 140, 26, p. 8162-8171
We demonstrate that molecular gradients on an organic monolayer is formed by preferential binding of ruthenium complexes from solutions also containing equimolar amounts of isostructural osmium complexes. The monolayer consists of a nanometer-thick assembly of 1,3,5-tris(4-pyridylethenyl)benzene (TPEB) covalently attached to a silicon or metal-oxide surface. The molecular gradient of ruthenium and osmium complexes is orthogonal to the surface plane. This gradient propagates throughout the molecular assembly with thicknesses over 30 nm. Using other monolayers consisting of closely related organic molecules or metal complexes results in the formation of molecular assemblies having an homogeneous and equimolar distribution of ruthenium and osmium complexes. Spectroscopic and computational studies revealed that the geometry of the complexes and the electronic properties of their ligands are nearly identical. These subtle differences cause the isostructural osmium and ruthenium complexes to pack differently on modified surfaces as also demonstrated in crystals grown from solution. The different packing behavior, combined with the organic monolayer significantly contributes to the observed differences in chemical composition on the surface.
Arnon Z. A., Pinotsi D., Schmidt M., Gilead S., Guterman T., Sadhanala A., Ahmad S., Levin A., Walther P., Kaminski C. F., Faendrich M., Schierle G. S. K., Adler-Abramovich L., Shimon L. J. W. & Gazit E. (2018) ACS Applied Materials and Interfaces. 10, 24, p. 20783-20789
Molecular self-assembly of short peptide building blocks leads to the formation of various material architectures that may possess unique physical properties. Recent studies had confirmed the key role of biaromaticity in peptide self-assembly, with the diphenylalanine (FF) structural family as an archetypal model. Another significant direction in the molecular engineering of peptide building blocks is the use of fluorenylmethoxycarbonyl (Fmoc) modification, which promotes the assembly process and may result in nanostructures with distinctive features and macroscopic hydrogel with supramolecular features and nanoscale order. Here, we explored the self-assembly of the protected, noncoded fluorenylmethoxycarbonyl-beta,beta-diphenyl-Ala-OH (Fmoc-Dip) amino acid. This process results in the formation of elongated needle-like crystals with notable aromatic continuity. By altering the assembly conditions, arrays of spherical particles were formed that exhibit strong light scattering. These arrays display vivid coloration, strongly resembling the appearance of opal gemstones. However, unlike the Rayleigh scattering effect produced by the arrangement of opal, the described optical phenomenon is attributed to Mie scattering. Moreover, by controlling the solution evaporation rate, i.e., the assembly kinetics, we were able to manipulate the resulting coloration. This work demonstrates a bottom-up approach, utilizing self-assembly of a protected amino acid minimal building block, to create arrays of organic, light-scattering colorful surfaces.
Zeng R., Feller M., Diskin-Posner Y., Shimon L. J. W., Ben-David Y. & Milstein D. (2018) Journal of the American Chemical Society. 140, 23, p. 7061-7064
Both CO and N2O are important, environmentally harmful industrial gases. The reaction of CO and N2O to produce CO2 and N-2 has stimulated much research interest aimed at degradation of these two gases in a single step. Herein, we report an efficient CO oxidation by N2O catalyzed by a (PNN)Ru-H pincer complex under mild conditions, even with no added base. The reaction is proposed to proceed through a sequence of O-atom transfer (OAT) from N2O to the Ru-H bond to form a Ru-OH intermediate, followed by intramolecular OH attack on an adjacent CO ligand, forming CO2 and N-2. Thus, the Ru-H bond of the catalyst plays a central role in facilitating the OAT from N2O to CO, providing an efficient and novel protocol for CO oxidation.
Brown N., Lei J., Zhan C., Shimon L. J. W., Adler-Abramovich L., Wei G. & Gazit E. (2018) ACS Nano. 12, 4, p. 3253-3262
Self-assembly is a process of key importance in natural systems and in nanotechnology. Peptides are attractive building blocks due to their relative facile synthesis, biocompatibility, and other unique properties. Diphenylalanine (FF) and its derivatives are known to form nanostructures of various architectures and interesting and varied characteristics. The larger triphenylalanine peptide (FFF) was found to self-assemble as efficiently as FF, forming related but distinct architectures of plate-like and spherical nanostructures. Here, to understand the effect of triaromatic systems on the self-assembly process, we examined carboxybenzyl-protected diphenylalanine (z-FF) as a minimal model for such an arrangement. We explored different self-assembly conditions by changing solvent compositions and peptide concentrations, generating a phase diagram for the assemblies. We discovered that z-FF can form a variety of structures, including nanowires, fibers, nanospheres, and nanotoroids, the latter were previously observed only in considerably larger or co-assembly systems. Secondary structure analysis revealed that all assemblies possessed a beta-sheet conformation. Additionally, in solvent combinations with high water ratios, z-FF formed rigid and self-healing hydrogels. X-ray crystallography revealed a "wishbone" structure, in which z-FF dimers are linked by hydrogen bonds mediated by methanol molecules, with a 2-fold screw symmetry along the c-axis. All-atom molecular dynamics (MD) simulations revealed conformations similar to the crystal structure. Coarse-grained MD simulated the assembly of the peptide into either fibers or spheres in different solvent systems, consistent with the experimental results. This work thus expands the building block library for the fabrication of nanostructures by peptide self-assembly.
Shankar S., Chovnik O., Shimon L. J. W., Lahav M. & van der Boom M. E. (2018) Crystal Growth and Design. 18, 4, p. 1967-1977
In this study we have used a tetrahedral oligopyridine and four different fluoroiodides to obtain three-dimensional (3D) nanoporous halogen-bonded cocrystals. Many of the halogen-bonded cocrystals reported to date are one-dimensional chains or two-dimensional sheet-like structures; these new cocrystals possess multiple channels of 300-800 Å
<sup>3</sup> volume per unit cell. The extended 3D channels can be designed by varying the molecular structure of the halogen bond donor and were found to occupy 20-40% of the unit cell volume. The N···I distances in our cocrystals are ∼80% of the sum of the van der Waals radii of the nitrogen and iodine atoms, and the N···I-C angles are nearly linear. Noncovalent stacking (π-π) interactions as well as H-bonding to solvents were also observed in some of the cocrystals. The supramolecular structures obtained in this study are effectively derived out of different donor-acceptor XB interactions, solvent and other noncovalent interactions. The weak nature of halogen bonds as well as the existence of multiple interactions make these cocrystal structures and their supramolecular organization difficult to predict. Even though this work does not attempt to single out the individual contributions of different factors affecting the supramolecular assemblies, we show here how the structure and hence the potential porosity of the halogen-bonded organic frameworks can be varied via careful design and combination of structurally different donors and acceptors.
Ranjan P., Shankar S., Popovitz-Biro R., Cohen S. R., Kaplan-Ashiri I., Dadosh T., Shimon L. J. W., Visic B., Tenne R., Lahav M. & van der Boom M. E. (2018) Journal of Physical Chemistry C. 122, 12, p. 6748-6759
We report here a unique and efficient methodology for the surface functionalization of closed-cage inorganic fullerene-like (IF) nanoparticles and inorganic nanotubes (INTs) composed of two-dimensional nanomaterials of transition-metal chalcogenides (MS
<sub>2</sub>; M = W or Mo). The first step is the physical coverage of these robust inorganic materials with monodispersed and dense monolayers of gold, silver, and palladium nanoparticles. The structural continuity at the interface between the IF/INT and the metallic nanoparticles is investigated. Lattice matching between these nanocrystalline materials and strong chemical affinity lead to efficient binding of the metallic nanoparticles onto the outer sulfide layer of the MS
<sub>2</sub>-based structures. It is shown that this functionalization results in narrowing of the IF/INT optical band gap, increased work function, and improved surface-enhanced Raman scattering. In the second step, functionalization of the surface-bound nanoparticles is carried out by a ligand-exchange reaction. This ligand exchange involving the tetraoctylammonium bromide capping layer and an alkyl thiol enhances the solubility (∼10×) of the otherwise nearly insoluble materials in organic solvents. The scope of this method is further demonstrated by introducing a ruthenium(II) polypyridyl complex on the surface of the surface-bound AuNPs to generate fluorescent multicomponent materials.
Samanta D., Galaktionova D., Gemen J., Shimon L. J. W., Diskin-Posner Y., Avram L., Kral P. & Klajn R. (2018) Nature Communications. 9, 1, p. 641, 641
Confining molecules to volumes only slightly larger than the molecules themselves can profoundly alter their properties. Molecular switches-entities that can be toggled between two or more forms upon exposure to an external stimulus-often require conformational freedom to isomerize. Therefore, placing these switches in confined spaces can render them non-operational. To preserve the switchability of these species under confinement, we work with a water-soluble coordination cage that is flexible enough to adapt its shape to the conformation of the encapsulated guest. We show that owing to its flexibility, the cage is not only capable of accommodating-and solubilizing in water-several light-responsive spiropyran-based molecular switches, but, more importantly, it also provides an environment suitable for the efficient, reversible photoisomerization of the bound guests. Our findings pave the way towards studying various molecular switching processes in confined environments.
Adler-Abramovich L., Arnon Z. A., Sui X., Azuri I., Cohen H., Hod O., Kronik L., Shimon L. J. W., Wagner H. D. & Gazit E. (2018) Advanced Materials. 30, 5, 1704551
One major challenge of functional material fabrication is combining flexibility, strength, and toughness. In several biological and artificial systems, these desired mechanical properties are achieved by hierarchical architectures and various forms of anisotropy, as found in bones and nacre. Here, it is reported that crystals of N-capped diphenylalanine, one of the most studied self-assembling systems in nanotechnology, exhibit well-ordered packing and diffraction of sub-angstrom resolution, yet display an exceptionally flexible nature. To explore this flexibility, the mechanical properties of individual crystals are evaluated, assisted by density functional theory calculations. High-resolution scanning electron microscopy reveals that the crystals are composed of layered self-assembled structures. The observed combination of strength, toughness, and flexibility can therefore be explained in terms of weak interactions between rigid layers. These crystals represent a novel class of self-assembled layered materials, which can be utilized for various technological applications, where a combination of usually contradictory mechanical properties is desired.
Roy A., Das P. J., Diskin-Posner Y., Firer M., Grynszpan F. & Montag M. (2018) New Journal of Chemistry. 42, 19, p. 15541-15545
The fluorescent dye syn-(Me,Me)bimane interacts with the biorelevant Na+ ion to form labile complexes, three of which were crystallographically characterized, exhibiting new modes of bimane coordination. In water, as well as in organic solvents, Na+ complexation induces the quenching of bimane fluorescence.
Zou Y., Chakraborty S., Nerush A., Oren D., Diskin-Posner Y., Ben-David Y. & Milstein D. (2018) ACS Catalysis. 8, 9, p. 8014-8019
Deoxygenative hydrogenation of amides to amines homogeneously catalyzed by a complex of an Earth-abundant metal is presented. This manganese-catalyzed reaction features high efficiency and selectivity. A plausible reaction mechanism, involving metal-ligand cooperation of the manganese pincer complex, is proposed based on NMR studies and relevant stoichiometric reactions.
Feller M., Ben-Ari E., Diskin-Posner Y. & Milstein D. (2018) Journal of Coordination Chemistry. 71, 11-13, p. 1679-1689
Herein we report the reversible activation of CO
<sub>2</sub> by the dearomatized complex [(
<sup>t</sup>BuPNP*)Ir(COE)] (1) and by the aromatized complex [(
<sup>t</sup>BuPNP)Ir(C
<sub>6</sub>H
<sub>5</sub>)] (2) via metal-ligand cooperation (MLC) (
<sup>t</sup>BuPN = 2,6-bis-(di-tert-butylphosphinomethyl)pyridine;
<sup>t</sup>BuPNP* = deprotonated PNP; COE = cyclooctadiene). The [1,3]-addition of CO
<sub>2</sub> to 1 and 2 is reversible at ambient temperature. While the dearomatized complex 1 reacts readily at ambient temperature with CO
<sub>2</sub> in THF or benzene, complex 2 reacts with CO
<sub>2</sub> upon heating in benzene at 80 °C or at ambient temperature in THF. The novel aromatized complex [(
<sup>t</sup>BuPNP)IrCl] (10) does not react with CO
<sub>2</sub>. Based on the reactivity patterns of 1, 2, and 10 with CO
<sub>2</sub>, we suggest that CO
<sub>2</sub> activation via MLC takes place only via the dearomatized species, and that in the case of 2 THF plays a role as a polar solvent in facilitating formation of the dearomatized hydrido phenyl complex intermediate (complex II).
Daw P., Kumar A., Espinosa-Jalapa N. A., Diskin-Posner Y., Ben-David Y. & Milstein D. (2018) ACS Catalysis. 8, 9, p. 7734-7741
Base-metal catalyzed dehydrogenative self-coupling of 2-amino alcohols to selectively form functionalized 2,5-substituted pyrazine derivatives is presented. Also, 2-substituted quinoxaline derivatives are synthesized by dehydrogenative coupling of 1,2-diaminobenzene and 1,2-diols. In both cases, water and hydrogen gas are formed as the sole byproducts. The reactions are catalyzed by acridine-based pincer complexes of earth-abundant manganese.
Milstein D., Das U., Chakraborty S. & Diskin-Posner Y. (2018) Angewandte Chemie - International Edition. 57, 41, p. 13444-13448
We have developed unprecedented methods for the direct transformation of primary alcohols to alkenes in the presence of hydrazine, and for the synthesis of mixed alkenes by the reaction of alcohols with hydrazones. The reactions are catalyzed by a manganese pincer complex and proceed in absence of added base or hydrogen acceptors, liberating dihydrogen, dinitrogen, and water as the only byproducts. The proposed mechanism, based on preparation of proposed intermediates and control experiments, suggests that the transformation occurs through metalligand cooperative N−H activation of a hydrazone intermediate.
Oren D., Diskin-Posner Y., Avrarn L., Feller M. & Milstein D. (2018) Organometallics. 37, 14, p. 2217-2221
The unique synthesis and reactivity of [(
<sup>R</sup>PNP∗)NiH] complexes (1a,b), based on metal-ligand cooperation (MLC), are presented (
<sup>R</sup>PNP∗ = deprotonated PNP ligand, R =
<sup>i</sup>Pr,
<sup>t</sup>Bu). Unexpectedly, the dearomatized complexes 1a,b were obtained by reduction of the dicationic complexes [(
<sup>R</sup>PNP)Ni(MeCN)](BF
<sub>4</sub>)
<sub>2</sub> with sodium amalgam or by reaction of the free ligand with Ni
<sup>0</sup>(COD)
<sub>2</sub>. Complex 1b reacts with CO via MLC, to give a rare case of a distorted-octahedral PNP-based pincer complex, the Ni(0) complex 3b. Complexes 1a,b also react with CO
<sub>2</sub> via MLC to form a rare example of η
<sup>1</sup> binding of CO
<sub>2</sub> to nickel, complexes 4a,b. An unusual CO
<sub>2</sub> cleavage process by complex 4b, involving C-O and C-P cleavage and C-C bond formation, led to the Ni-CO complex 3b and to the new complex [(P
<sup>i</sup>Pr
<sub>2</sub>NC
<sub>2</sub>O
<sub>2</sub>)Ni(P(O)
<sup>i</sup>Pr
<sub>2</sub>)] (5b). All complexes have been fully characterized by NMR and X-ray crystallography.
Curland S., Meirzadeh E. & Diskin-Posner Y. (2018) Acta Crystallographica Section E: Crystallographic Communications. 74, p. 776-779
A new polymorph of (2S,3S)-2-amino-3-methylpentanoic acid, l-isoleucine C6H13NO2, crystallizes in the monoclinic space group P2(1) with four independent molecules in the asymmetric unit. The molecules are zwitterions. In the crystal, N-H center dot center dot center dot O hydrogen bonds link two pairs of independent molecules and their symmetry-related counterparts to form two types of layers stacked in an anti-parallel manner parallel to (001). The hydrophobic aliphatic isopropyl groups protrude from these layers.
Kumar A., Feller M., Ben-David Y., Diskin-Posner Y. & Milstein D. (2018) Chemical Communications. 54, 42, p. 5365-5368
The first example of oxidative addition of a C-H bond to a square planar d8-Iridium complex, without any external additive, such as an acid, is described. Our mechanistic investigations show that metal-ligand cooperation through aromatization-dearomatization of the lutidine backbone is involved in this process, and that the actual C-H activation step occurs through an Ir(iii) intermediate.
Milstein D., Das U. K., Ben-David Y. & Diskin-Posner Y. (2018) Angewandte Chemie - International Edition. 57, 8, p. 2179-2182
An unprecedented one-step synthesis of N-substituted hydrazones by coupling of alcohols with hydrazine is reported. This partial hydrogen-borrowing reaction is catalyzed by a new manganese pincer complex under mild reaction conditions, thus liberating water and dihydrogen as the only byproducts. Mechanistic insight, based on the observation of intermediates, is provided.
Espinosa Jalapa N. A., Nerush A., Shimon L. J. W., Leitus G., Avram L., Ben-David Y. & Milstein D. (2017) Chemistry - A European Journal. 23, 25, p. 5934-5938
Homogeneous catalytic hydrogenation of esters to alcohols is an industrially important, environmentally benign reaction. While precious metal-based catalysts for this reaction are now well known, only very few catalysts based on first-row metal complexes were reported. Here we present the hydrogenation of esters catalyzed by a complex of earth-abundant manganese. The reaction proceeds under mild conditions and insight into the mechanism is provided based on an NMR study and the synthesis of novel Mn complexes postulated as intermediates.
Das U. K., Shimon L. J. W. & Milstein D. (2017) Chemical Communications. 53, 98, p. 13133-13136
A transition metal free, straightforward synthetic method for the preparation of substituted imidazoles is reported herein. Base promoted, deaminative coupling of benzylamines with nitriles results in the one-step synthesis of 2,4,5-trisubstituted imidazoles with liberation of ammonia. This protocol provides a practical strategy for the synthesis of valuable imidazole derivatives from readily available starting materials.
Khenkin A. M., Vedichi M., Shimon L. J. W., Cranswick M. A., Klein J. E. M. N., Que L. & Neumann R. (2017) Israel Journal of Chemistry. 57, 10-11, p. 990-998
The iron(II) triflate complex (1) of 1,2-bis(2,2'-bipyridyl-6-yl)ethane, with two bipyridine moieties connected by an ethane bridge, was prepared. Addition of aqueous 30% H2O2 to an acetonitrile solution of 1 yielded 2, a green compound with lambda(max)=710 nm. Moessbauer measurements on 2 showed a doublet with an isomer shift (delta) of 0.35 mm/s and a quadrupole splitting (Delta E-Q) of 0.86 mm/s, indicative of an antiferromagnetically coupled diferric complex. Resonance Raman spectra showed peaks at 883, 556 and 451 cm(-1) that downshifted to 832, 540 and 441 cm-(1) when 1 was treated with (H2O2)-O-18. All the spectroscopic data support the initial formation of a (m-hydroxo)(mu-1,2-peroxo) diiron(III) complex that oxidizes carbon-hydrogen bonds. At 0 degrees C 2 reacted with cyclohexene to yield allylic oxidation products but not epoxide. Weak benzylic C-H bonds of alkylarenes were also oxidized. A plot of the logarithms of the second order rate constants versus the bond dissociation energies of the cleaved C-H bond showed an excellent linear correlation. Along with the observation that oxidation of the probe substrate 2,2-dimethyl-1-phenylpropan-1-ol yielded the corresponding ketone but no benzaldehyde, and the kinetic isotope effect, k(H)/k(D), of 2.8 found for the oxidation of xanthene, the results support the hypothesis for a metal-based H-atom abstraction mechanism. Complex 2 is a rare example of a (m-hydroxo)(mu-1,2-peroxo) diiron(III) complex that can elicit the oxidation of carbon-hydrogen bonds.
Pellach M., Mondal S., Harlos K., Mance D., Baldus M., Gazit E. & Shimon L. J. W. (2017) ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 56, 12, p. 3252-3255
The crystal structure of a designed phospholipid-inspired amphiphilic phosphopeptide at 0.8 angstrom resolution is presented. The phosphorylated beta-hairpin peptide crystallizes to form a lamellar structure that is stabilized by intra-and intermolecular hydrogen bonding, including an extended beta-sheet structure, as well as aromatic interactions. This first reported crystal structure of a two-tailed peptidic bilayer reveals similarities in thickness to a typical phospholipid bilayer. However, water molecules interact with the phosphopeptide in the hydrophilic region of the lattice. Additionally, solid-state NMR was used to demonstrate correlation between the crystal structure and supramolecular nanostructures. The phosphopeptide was shown to self-assemble into semi-elliptical nanosheets, and solid-state NMR provides insight into the self-assembly mechanisms. This work brings a new dimension to the structural study of biomimetic amphiphilic peptides with determination of molecular organization at the atomic level.
Gadakh S., Shimon L. J. W. & Gidron O. (2017) ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 56, 44, p. 13601-13605
We demonstrate the transformation of oligofurans through sequential Diels-Alder cycloaddition reactions to provide oligoarenes in two chemical steps, regardless of the oligomer length. By this method, oligonaphthalenes containing up to six units were obtained in high yield through the formation of up to 12 new C-C bonds. The versatility of this method was demonstrated for various polyaromatic hydrocarbons. The regioselectivity of this process enabled the synthesis of a library of substituted triarylenes from a single terfuran precursor by modification of the dienophile strength and the order of addition. Overall, this study demonstrates that long oligofurans are interesting not only as organic electronic materials, but also as starting materials for the formation of various conjugated systems.
Salama M., Shterenberg I., Shimon L. J. W., Keinan-Adamsky K., Afri M., Gofer Y. & Aurbach D. (2017) Journal of Physical Chemistry C. 121, 45, p. 24909-24918
Recently, MgTFSI2/MgCl2 electrolyte solutions in dimethoxyethane (DME) have been shown to function as viable electrolyte solutions for secondary Mg batteries that can facilitate reversible magnesium deposition/dissolution. MgCl2 is a crucial component in these solutions. On its own, however, it is practically insoluble in DME. Therefore, the fact that it is readily dissolved in MgTFSI2/DME solution is remarkable. Addition of MgCl2 greatly improves the electrochemical performance of MgTFSI2/DME electrolyte solutions. Thus, identifying the species formed in MgTFSI2/MgCl2 solutions is intriguing. In this study, we implemented a wide variety of analytical tools, including single crystal X-ray diffraction, multinuclear NMR, and Raman spectroscopy, to elucidate the structure of these solutions. Various solution species were determined, and a suitable reaction scheme is suggested.
Somekh M., Cohen H., Diskin-Posner Y., Shimon L. J. W., Carmieli R., Rosenberg J. N. & Neumann R. (2017) ACS Catalysis. 7, 4, p. 2725-2729
The valorization of alkanes is possible via carbon carbon coupling reactions. A series of dialkyl cobalt complexes RRCH2)(2)Co-III(bpy)(2)]ClO4 (R = H, Me, Et, and Ph) were reacted with the H5PV2Mo10O40 polyoxometalate as a catalyst, leading to a selective oxidative carbon carbon bond coupling reaction. The reaction is initiated by electron transfer from [(RCH2)(2)Co-III(bpy)(2)](+) to (H5PV2Mo10O40)-Mo-V to yield an intermediate [(RCH2)(2)Co-IV(bpy)(2)](2+)-(H5PVVMo10O40)-V-IV-Mo-V, as identified by a combination of EPR and X-ray photoelectron spectroscopy experiments. The reaction is catalytic with O-2 as terminal oxidant representing an aerobic C-C bond coupling reaction.
Schnaider L., Brahmachari S., Schmidt N. W., Mensa B., Shaham-Niv S., Bychenko D., Adler-Abramovich L., Shimon L. J. W., Kolusheva S., DeGrado W. F. & Gazit E. (2017) Nature Communications. 8, 1, 1365
Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials.
Gilboa B., Lafargue C., Handelman A., Shimon L. J., Rosenman G., Zyss J. & Ellenbogen T. (2017) Advanced Science. 4, 9, 1700052
Short peptides made from repeating units of phenylalanine self-assemble into a remarkable variety of micro- and nanostructures including tubes, tapes, spheres, and fibrils. These bio-organic structures are found to possess striking mechanical, electrical, and optical properties, which are rarely seen in organic materials, and are therefore shown useful for diverse applications including regenerative medicine, targeted drug delivery, and biocompatible fluorescent probes. Consequently, finding new optical properties in these materials can significantly advance their practical use, for example, by allowing new ways to visualize, manipulate, and utilize them in new, in vivo, sensing applications. Here, by leveraging a unique electro-optic phase microscopy technique, combined with traditional structural analysis, it is measured in di- and triphenylalanine peptide structures a surprisingly large electro-optic response of the same order as the best performing inorganic crystals. In addition, spontaneous domain formation is observed in triphenylalanine tapes, and the origin of their electro-optic activity is unveiled to be related to a porous triclinic structure, with extensive antiparallel beta-sheet arrangement. The strong electro-optic response of these porous peptide structures with the capability of hosting guest molecules opens the door to create new biocompatible, environmental friendly functional materials for electro-optic applications, including biomedical imaging, sensing, and optical manipulation.
Mondal S., Varenik M., Bloch D., Atsmon-Raz Y., Jacoby G., Adler-Abramovich L., Shimon L., Beck R., Miller Y., Regev O. & Gazit E. (2017) Nature Communications. 8, 14018
Extensive work has been invested in the design of bio-inspired peptide emulsifiers. Yet, none of the formulated surfactants were based on the utilization of the robust conformation and self-assembly tendencies presented by the hydrophobins, which exhibited highest surface activity among all known proteins. Here we show that a minimalist design scheme could be employed to fabricate rigid helical peptides to mimic the rigid conformation and the helical amphipathic organization. These designer building blocks, containing natural non-coded α-aminoisobutyric acid (Aib), form superhelical assemblies as confirmed by crystallography and microscopy. The peptide sequence is amenable to structural modularity and provides the highest stable emulsions reported so far for peptide and protein emulsifiers. Moreover, we establish the ability of short peptides to perform the dual functions of emulsifiers and thickeners, a feature that typically requires synergistic effects of surfactants and polysaccharides. This work provides a different paradigm for the molecular engineering of bioemulsifiers.
Haviv E., Shimon L. J. & Neumann R. (2017) Chemistry-A European Journal. 23, 1, p. 92-95
The photochemical reduction of CO<sub>2</sub> to CO requires two electrons and two protons that, in the past, have been derived from sacrificial amine donors that are also non-innocent in the catalytic cycle. Towards the realization of a water-splitting reaction as the source of electrons and protons for CO<sub>2</sub> reduction, we have found that a reduced acidic polyoxometalate, H<sub>5</sub>PW<sup>V</sup> <sub>2</sub>W<sub>10</sub>O<sub>40</sub>, is a photoactive electron and proton donor with visible light through excitation of the intervalence charge-transfer band. Upon linking the polyoxometalate to a dirhenium molecular catalyst, a cascade of transformations occurs where the polyoxometalate is electrochemically reduced at a relatively low negative potential of 1.3 V versus Ag/AgNO<sub>3</sub> and visible light, a 60 W tungsten lamp, or a red LED is used to transfer electrons from the polyoxometalate to the dirhenium catalyst active for the selective reduction of CO<sub>2</sub> to CO.
Sharon D., Sharon P., Hirshberg D., Salama M., Afri M., Shimon L. J., Kwak W. J., Sun Y. K., Frimer A. A. & Aurbach D. (2017) Journal of the American Chemical Society. 139, 34, p. 11690-11693
In this study, we present a new aprotic solvent, 2,4-dimethoxy-2,4-dimethylpentan-3-one (DMDMP), which is designed to resist nucleophilic attack and hydrogen abstraction by reduced oxygen species. Li-O<sub>2</sub> cells using DMDMP solutions were successfully cycled. By various analytical measurements, we showed that even after prolonged cycling only a negligible amount of DMDMP was degraded. We suggest that the observed capacity fading of the Li-O<sub>2</sub> DMDMP-based cells was due to instability of the lithium anode during cycling. The stability toward oxygen species makes DMDMP an excellent solvent candidate for many kinds of electrochemical systems which involve oxygen reduction and assorted evaluation reactions.
Elool Dov N., Shankar S., Cohen D., Bendikov T., Rechav K., Shimon L. J. W., Lahav M. & van der Boom M. E. (2017) Journal of the American Chemical Society. 139, 33, p. 11471-11481
In this study, we demonstrate a versatile approach for the formation of electrochromic nanoscale assemblies on transparent conductive oxides on both rigid and flexible substrates. Our method is based on the application of alternating spin-coated layers of well-defined metal polypyridyl complexes and a palladium(II) salt to form electrochemically addressable films with a high chromophore density. By varying the central metal ion of the polypyridyl complexes (Os, Ru, and" Fe) and their ligands and by mixing these complexes, coatings with a wide range of colors can be achieved. These coatings cover a large area of RGB color space. The coloration intensities of these nanoscale films can be tuned by "the number of deposition steps. The materials have very attractive ON/OFF ratios, electrochemical stabilities, and coloration efficiencies. Reversible color-to-colorless and color-to-color transitions were demonstrated, and the films were further integrated into sandwich cells.
Daw P., Chakraborty S., Leitus G., Diskin-Posner Y., Ben David Y. & Milstein D. (2017) ACS Catalysis. 7, 4, p. 2500-2504
N-formylation of amines utilizing CO2 in the presence of reducing agents constitute an important methodology in organic synthesis. Presented herein is a selective N-formylation of amines with CO2 and H-2 catalyzed by complexes of Earth-abundant cobalt. A wide range of amines were converted to their corresponding formamides under CO2 and H-2 pressure, catalyzed by Co-PNP pincer complex, generating water as the sole byproduct.
Dauth A., Gellrich U., Diskin-Posner Y., Ben-David Y. & Milstein D. (2017) Journal of the American Chemical Society. 139, 7, p. 2799-2807
A ferraquinone-ferrahydroquinone organometallic redox couple was prepared and characterized. Intricate cooperativity of the metal was observed with different positions on the ligand. This allowed cooperative activation of small molecules like molecular hydrogen, oxygen, and bromine. Likewise, dehydrogenation of alcohols was achieved through 1,6 metal ligand cooperation.
Kumar A., Espinosa-Jalapa N. A., Leitus G., Diskin-Posner Y., Avram L. & Milstein D. (2017) Angewandte Chemie - International Edition. 56, 47, p. 14992-14996
The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable.
Espinosa Jalapa N. A., Kumar A., Leitus G., Diskin Posner Y. & Milstein D. (2017) Journal of the American Chemical Society. 139, 34, p. 11722-11725
The first example of base-metal-catalyzed dehydrogenative coupling of diols and amines to form cyclic imides is reported. The reaction is catalyzed by a pincer complex of the earth abundant manganese and forms hydrogen gas as the sole byproduct, making the overall process atom economical and environmentally benign.
Chakraborty S., Gellrich U., Diskin Posner Y., Leitus G., Avram L. & Milstein D. (2017) Angewandte Chemie - International Edition. 56, 15, p. 4229-4233
The first example of a base metal (manganese) catalyzed acceptorless dehydrogenative coupling of methanol and amines to form formamides is reported herein. The novel pincer complex (iPr-PN<sup>H</sup>P)Mn(H)(CO)<sub>2</sub> catalyzes the reaction under mild conditions in the absence of any additives, bases, or hydrogen acceptors. Mechanistic insight based on the observation of an intermediate and DFT calculations is also provided.
Fichman G., Guterman T., Damron J., Adler-Abramovich L., Schmidt J., Kesselman E., Shimon L. J. W., Ramamoorthy A., Talmon Y. & Gazit E. (2016) Science Advances. 2, 2, 1500827
The association of building blocks into supramolecular polymers allows the fabrication of diverse functional architectures at the nanoscale. The use of minimal assembly units to explore polymer dynamics and phase transitions significantly contributes to the application of polymer physicochemical paradigms in the field of supramolecular polymers. We present a minimal model that displays spontaneous coordinated structural transitions between micro-and nanostructures, hydrogels with nanoscale order, and single crystals. The simple amphiphilic 9-fluorenylmethoxycarbonyl-3,4-dihydroxyphenylalanine (Fmoc-DOPA) modified amino acid undergoes a noninduced transition from spherical assemblies into nanofibrils followed by sol-gel transition, nanotube formation via intermediate assembly, and crystallization within the gel. Notably, the transition kinetics is slow enough to allow both multistage and multiscale characterization of the supramolecular arrangement using electron microscopy, vibrational and circular dichroism spectroscopies, nuclear magnetic resonance, and x-ray crystallography. This minimalistic system is the first comprehensive model for a complete spontaneous structural transition between diverse states governed by distinct molecular interactions.
Shoken D., Shimon L. J. W., Tamm M. & Eisen M. S. (2016) Organometallics. 35, 8, p. 1125-1131
The synthesis of mixed (aryloxo)(imidazolin-2-inainato)-titanium dichloride complexes is presented. Full characterization of the complexes, including solid-state X-ray diffraction analysis of four complexes, is reported. Their catalytic activity in the polymerization of ethylene, propylene, 1-hexene, and 1-octene was studied. The different substituents at the aryloxo moiety were found to have a substantial impact on the reactivity of the complexes, indicating the need for a balance of steric and electronic effects. The complex (1,3-di-tert-butylimidazolin-2-iminato)(2,6-di-tert-butyl-4-methylphenoxide)-titanium dichloride (1) was found to be the most active in the polymerization of ethylene, whereas the complex (1,3-di-tert-butylimidazolin-2-iminato)(2,6-di-tert-butylphenoxide)titanium dichloride (2) was found to be the most active in the polymerization of propylene. Interestingly, all complexes were more active in the polymerization of propylene than in that of ethylene.
Guterman T., Kornreich M., Stern A., Adler-Abramovich L., Porath D., Beck R., Shimon L. J. W. & Gazit E. (2016) Nat Commun. 7, 13482
Mimicking the multifunctional bacterial type IV pili (T4Ps) nanofibres provides an important avenue towards the development of new functional nanostructured biomaterials. Yet, the development of T4Ps-based applications is limited by the inability to form these nanofibres in vitro from their pilin monomers. Here, to overcome this limitation, we followed a reductionist approach and designed a self-assembling pilin-based 20-mer peptide, derived from the presumably bioelectronic pilin of Geobacter sulfurreducens. The designed 20-mer, which spans sequences from both the polymerization domain and the functionality region of the pilin, self-assembled into ordered nanofibres. Investigation of the 20-mer revealed that shorter sequences which correspond to the polymerization domain form a supramolecular b-sheet, contrary to their helical configuration in the native T4P core, due to alternative molecular recognition. In contrast, the sequence derived from the functionality region maintains a native-like, helical conformation. This study presents a new family of self-assembling peptides which form T4P-like nanostructures.
Shahar C., Dutta S., Weissman H., Shimon L. J. W., Ott H. & Rybtchinski B. (2016) Angewandte Chemie (International ed. in English). 55, 1, p. 179-182
Understanding and controlling organic crystallization in solution is a long-standing challenge. Herein, we show that crystallization of an aromatic amphiphile based on perylene diimide in aqueous media involves initially formed amorphous spherical aggregates that evolve into the crystalline phase. The initial appearance of the crystalline order is always confined to the spherical aggregates that are precursors for crystalline evolution. The change in the solvation of the prenucleation phase drives the crystallization process towards crystals that exhibit very different structure and photofunction. The initial molecular structure and subsequent crystal evolution can be regulated by tuning the hydrophobicity at various stages of crystallization, affording dissimilar crystalline products or hindering crystallization. Thus, the key role of the precrystalline states in organic crystal evolution enables a new strategy to control crystallization by precrystalline state manipulation.
Xie Y., Ben-David Y., Shimon L. J. & Milstein D. (2016) Journal of the American Chemical Society. 138, 29, p. 9077-9080, 138
A highly efficient ruthenium pincer-catalyzed Guerbet-type process for the production of biofuel from ethanol has been developed. It produces the highest conversion of ethanol (73.4%, 0.02 mol% catalyst) for a Guerbet-type reaction, including significant amounts of C<sub>4</sub> (35.8% yield), C<sub>6</sub> (28.2% yield), and C<sub>8</sub> (9.4% yield) alcohols. Catalyst loadings as low as 0.001 mol% can be used, leading to a record turnover number of 18 »209. Mechanistic studies reveal the likely active ruthenium species and the main deactivation process.
Pellach M., Mondal S., Shimon L. J., Adler-Abramovich L., Buzhansky L. & Gazit E. (2016) Chemistry of Materials. 28, 12, p. 4341-4348
Diphenylalanine is one of the most studied building blocks in organic supramolecular chemistry, forming ordered assemblies with unique mechanical, optical, piezoelectric, and semiconductive properties. These structures are being used for diverse applications, including energy storage, biosensing, light emission, drug delivery, artificial photosynthesis, and chemical propulsion. To increase the structural diversity of this dipeptide building block, three previously unreported analogues in which the aliphatic chain between the peptide backbone and the phenyl ring was gradually lengthened were synthesized. Each dipeptide self-assembled into unique microstructures, differing in morphology, which ranged from flat plates to long microrods to flattened microplanks. The structures were also found to possess distinctive optical properties. Furthermore, X-ray crystallography of each of the three diphenylalanine analogues presented distinctive molecular arrangements. The remarkable differences between each dipeptide in the intermolecular interactions they formed provide insight into the physicochemical mechanisms of self-assembly and, in addition, indicate the biological significance of the single methylene bridge of phenylalanine.
Mukherjee A., Nerush A., Leitus G., Shimon L. J. W., Ben-David Y., Jalapa N. A. E. & Milstein D. (2016) Journal of the American Chemical Society. 138, 13, p. 4298-4301
The catalytic dehydrogenative coupling of alcohols and amines to form aldimines represents an environmentally benign methodology in organic chemistry. This has been accomplished in recent years mainly with precious-metal-based catalysts. We present the dehydrogenative coupling of alcohols and amines to form imines and H<sub>2</sub> that is catalyzed, for the first time, by a complex of the earth-abundant Mn. Detailed mechanistic study was carried out with the aid of NMR spectroscopy, intermediate isolation, and X-ray analysis.
Gellrich U., Diskin Posner Y., Shimon L. J. W. & Milstein D. (2016) Journal of the American Chemical Society. 138, 40, p. 13307-13313
Aromaticity is a central concept in chemistry. Reaction pathways involving reversible ligand dearomatization sequences emerged as a powerful tool for bond activation by metal complexes. Exploring this concept with a metal-free system, we have synthesized a pyridine-coordinated aminoborane which undergoes a temperature-induced formal dearomatization of the pyridine ring. NMR studies and DFT calculations revealed that this formal dearomatization sequence led to an aromaticity switch and the formation of a six-π-electron boron-containing heteroaromatic system. Disrupting this aromatic system by coordination of an amine or a carboxylic acid to the boron center enabled N-H activation and O-H cleavage, leading to an unprecedented reversal aromaticity switch.
Anaby A., Feller M., Ben-David Y., Leitus G., Diskin Posner Y., Shimon L. J. W. & Milstein D. (2016) Journal of the American Chemical Society. 138, 31, p. 9941-9950
The use of carbon dioxide for synthetic applications presents a major goal in modern homogeneous catalysis. Rhodium-hydride PNP pincer complex 1 is shown to add CO<sub>2</sub> in two disparate pathways: one is the expected insertion of CO<sub>2</sub> into the metal-hydride bond, and the other leads to reductive cleavage of CO<sub>2</sub>, involving metal-ligand cooperation. The resultant rhodium-carbonyl complex was found to be photoactive, enabling the activation of benzene and formation of a new benzoyl complex. Organometallic intermediate species were observed and characterized by NMR spectroscopy and X-ray crystallography. Based on the series of individual transformations, a sequence for the photocarbonylation of benzene using CO<sub>2</sub> as the feedstock was constructed and demonstrated for the production of benzaldehyde from benzene.
Milstein D., Rivada Wheelaghan O., Chakraborty S., Shimon L. J. W. & Ben-David Y. (2016) Angewandte Chemie - International Edition. 55, 24, p. 6942-6945
Efficient iron-catalyzed homocoupling of terminal alkynes and cross-dimerization of aryl acetylenes with trimethylsilylacetylene is reported. The complex [Fe(H)(BH4 )(iPr-PNP)] (1) catalyzed the (cross-)dimerization of alkynes at room temperature, with no need for a base or other additives, to give the corresponding dimerized products with Z selectivity in excellent yields (79-99%).
Das P. J., Diskin-Posner Y., Firer M., Montag M. & Grynszpan F. (2016) Dalton Transactions. 45, 43, p. 17123-17131
A cationic Pd(ii) complex containing syn-(Me,Me)bimane as a ligand was prepared and fully characterized. This complex represents the first well-defined case of a bimane scaffold coordinated to a metal center. The strongly-fluorescent syn-bimane chelates the Pd(ii) center via its carbonyl oxygen atoms, affording a non-fluorescent complex. The crystal structure of this complex shows that the coordinated bimane departs from planarity, with its bicyclic framework bent about the N-N bond. Spectroscopic evidence demonstrates that bimane coordination is reversible in solution.
Butschke B., Feller M., Diskin Posner Y. & Milstein D. (2016) Catalysis Science and Technology. 6, 12, p. 4428-4437
The formal Fe<sup>II</sup>-hydride complex [Fe(H)(CO)(MeCN)L<sub>PNN</sub>](BF<sub>4</sub>) (1) (L<sub>PNN</sub> = 2-[(di-tert-butylphosphino)methyl]-6-[1-(mesitylimino)ethyl]pyridine) catalyzes the hydrogenation of ketones under mild conditions (room temperature, p(H<sub>2</sub>) = 4 bar) and short reaction times (1-3 h) in the presence of catalytic amounts of KHMDS as a base. The reaction presumably proceeds via a dearomatization/rearomatization mechanism. However, in comparison with the reaction of related iron-PNP complexes, the reaction mechanism seems to be different, and an enolate formation step appears to precede catalysis. Moreover, the catalytic performance of the PNN system is inferior under similar conditions, and this observation is probably a consequence of an intramolecular deactivation pathway, which involves reductive proton migration within a dearomatized Fe<sup>II</sup>-hydride complex to form a catalytically inactive Fe<sup>0</sup> species. The weaker electron-donating properties of the PNN ligand system, when compared with analogous PNP-based ligands, cause the dearomatized PNN iron(ii)-hydride intermediate to be less electron-rich and consequently more prone to the intramolecular reductive elimination pathway. This result is in line with the need for electron-rich metal hydrides for efficient hydrogenation catalysis to take place.
Feller M., Milstein D., Gellrich U., Anaby A. & Diskin Posner Y. (2016) Journal of the American Chemical Society. 138, 20, p. 6445-6454
A unique mode of stoichiometric CO<sub>2</sub> activation and reductive splitting based on metal-ligand-cooperation is described. The novel Ir hydride complexes [(<sup>t</sup>Bu-PNP)Ir(H)<sub>2</sub>] (2) (<sup>t</sup>Bu-PNP, deprotonated <sup>t</sup>Bu-PNP ligand) and [(<sup>t</sup>Bu-PNP)Ir(H)] (3) react with CO<sub>2</sub> to give the dearomatized complex [(<sup>t</sup>Bu-PNP)Ir(CO)] (4) and water. Mechanistic studies have identified an adduct in which CO<sub>2</sub> is bound to the ligand and metal, [(<sup>t</sup>Bu-PNP-COO)Ir(H)<sub>2</sub>] (5), and a di-CO<sub>2</sub> iridacycle [(<sup>t</sup>Bu-PNP)Ir(H)(C<sub>2</sub>O<sub>4</sub>-<sub>C,O</sub>)] (6). DFT calculations confirm the formation of 5 and 6 as reversibly formed side products, and suggest an <sup>1</sup>-CO<sub>2</sub> intermediate leading to the thermodynamic product 4. The calculations support a metal-ligand-cooperation pathway in which an internal deprotonation of the benzylic position by the η<sup>1</sup>-CO<sub>2</sub> ligand leads to a carboxylate intermediate, which further reacts with the hydride ligand to give complex 4 and water.
Krupkin M., Wekselman I., Matzov D., Eyal Z., Posner Y. D., Rozenberg H., Zimmerman E., Bashan A. & Yonath A. (2016) Proceedings of the National Academy of Sciences of the United States of America. 113, 44, p. E6796-E6805
Two structurally unique ribosomal antibiotics belonging to the orthosomycin family, avilamycin and evernimicin, possess activity against Enterococci, Staphylococci, and Streptococci, and other Gram-positive bacteria. Here, we describe the high-resolution crystal structures of the eubacterial large ribosomal subunit in complex with them. Their extended binding sites span the A-tRNA entrance corridor, thus inhibiting protein biosynthesis by blocking the binding site of the A-tRNA elbow, a mechanism not shared with other known antibiotics. Along with using the ribosomal components that bind and discriminate the A-tRNA-namely, ribosomal RNA (rRNA) helices H89, H91, and ribosomal proteins (rProtein) uL16-these structures revealed novel interactions with domain 2 of the CTC protein, a feature typical to various Gram-positive bacteria. Furthermore, analysis of these structures explained how single nucleotide mutations and methylations in helices H89 and H91 confer resistance to orthosomycins and revealed the sequence variations in 23S rRNA nucleotides alongside the difference in the lengths of the eukaryotic and prokaryotic α1 helix of protein uL16 that play a key role in the selectivity of those drugs. The accurate interpretation of the crystal structures that could be performed beyond that recently reported in cryo-EM models provide structural insights that may be useful for the design of novel pathogen-specific antibiotics, and for improving the potency of orthosomycins. Because both drugs are extensively metabolized in vivo, their environmental toxicity is very low, thus placing them at the frontline of drugs with reduced ecological hazards.
Berger O., Adler-Abramovich L., Levy-Sakin M., Grunwald A., Liebes-Peer Y., Bachar M., Buzhansky L., Mossou E., Forsyth V. T., Schwartz T., Ebenstein Y., Frolow F., Shimon L. J., Patolsky F. & Gazit E. (2015) Nature Nanotechnology. 10, 4, p. 353-360
The two main branches of bionanotechnology involve the self-assembly of either peptides or DNA. Peptide scaffolds offer chemical versatility, architectural flexibility and structural complexity, but they lack the precise base pairing and molecular recognition available with nucleic acid assemblies. Here, inspired by the ability of aromatic dipeptides to form ordered nanostructures with unique physical properties, we explore the assembly of peptide nucleic acids (PNAs), which are short DNA mimics that have an amide backbone. All 16 combinations of the very short di-PNA building blocks were synthesized and assayed for their ability to self-associate. Only three guanine-containing di-PNAs - CG, GC and GG - could form ordered assemblies, as observed by electron microscopy, and these di-PNAs efficiently assembled into discrete architectures within a few minutes. The X-ray crystal structure of the GC di-PNA showed the occurrence of both stacking interactions and Watson-Crick base pairing. The assemblies were also found to exhibit optical properties including voltage-dependent electroluminescence and wide-range excitation-dependent fluorescence in the visible region.
Toledo H., Amar M., Bar S., Iron M. A., Fridman N., Tumanskii B., Shimon L. J., Botoshansky M. & Szpilman A. M. (2015) Organic and Biomolecular Chemistry. 13, 43, p. 10726-10733
Nitroxides (nitroxyl radicals) hold a unique place in science due to their stable radical nature. We have recently reported the first design concept providing a general solution to the problem of designing and preparing monocyclic α-hydrogen nitroxides. The initial studies were limited to aryl derivatives. We now report a wider study showing that alkyl substituents may be employed as well. In addition, we report several additional examples of aryl substituents and reveal some of the structural limitations with regard to nitroxide stability as a function of the α-carbon substituent.
Meltzer D., Gottlieb H. E., Amir A., Shimon L. J. & Fischer B. (2015) Dalton Transactions. 44, 48, p. 21073-21080
Hybrids of methylenediphosphonotetrathioate and crown-ether (MDPT-CE) were synthesized forming 7-,8-,9-,10- and 13-membered rings. Both 7- and 13-membered ring-containing compounds were found to be highly stable to air-oxidation for at least four weeks. These hybrids bind Zn(ii) by both MDPT and CE moieties, forming a 2 : 1 L : Zn(ii) complex. Interestingly, the 13-membered ring MDPT-CE showing a high affinity to Zn(ii) (K<sub>a</sub> 3 ± 0.5 × 10<sup>6</sup> mol<sup>-2</sup> L<sup>2</sup>) does not bind Li(i) or Na(i). The 13-Membered MDPT-CE hybrid is a promising water-soluble, air-stable, high-affinity Zn(ii)-chelator, exhibiting selectivity to Zn(ii) vs. Mg(ii), Na(i), and Li(i).
Srimani D., Mukherjee A., Goldberg A. F. G., Leitus G., Diskin Posner Y., Shimon L. J. W., Ben-David Y. & Milstein D. (2015) Angewandte Chemie - International Edition. 54, 42, p. 12357-12360
The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.
Shirman T., Boterashvili M., Orbach M., Freeman D., Shimon L. J. W., Lahav M. & van der Boom M. E. (2015) Crystal Growth and Design. 15, 10, p. 4756-4759
The prediction of supramolecular structures involving different weak interactions is challenging. In this study, single-atom modifications to the molecular structure allow us to address their hierarchy. The resulting series of unimolecular assemblies are mainly based on halogen bonding (XB), hydrogen bonding (HB), or a combination of both. By varying the XB donor (F, Cl, Br, and I) and the XB and HB acceptors (pyridine vs pyridine-N-oxide) we can control the primary motifs directing the structure.
Voronov-Goldman M., Yaniv O., Gul O., Yoffe H., Salama-Alber O., Slutzki M., Levy-Assaraf M., Jindou S., Shimon L. J. W., Borovok I., Bayer E., Lamed R. & Frolow F. (2015) FEBS Letters. 589, 14, p. 1569-1576
The cellulolytic bacterium Ruminococcus flavefaciens of the herbivore rumen produces an elaborate cellulosome system, anchored to the bacterial cell wall via the covalently bound scaffoldin ScaE. Dockerin-bearing scaffoldins also bind to an autonomous cohesin of unknown function, called cohesin G (CohG). Here, we demonstrate that CohG binds to the scaffoldin-borne dockerin in opposite orientation on a distinct site, relative to that of ScaE. Based on these structural data, we propose that the complexed dockerin is still available to bind ScaE on the cell surface. CohG may thus serve as a molecular shuttle for delivery of scaffoldins to the bacterial cell surface.
Butschke B., Fillman K. L., Bendikov T., Shimon L. J. W., Diskin Posner Y., Leitus G., Gorelsky S. I., Neidig M. L. & Milstein D. (2015) Inorganic Chemistry. 54, 10, p. 4909-4926
Herein we present a series of new α-iminopyridine-based iron-PNN pincer complexes [FeBr<sub>2</sub>L<sub>PNN</sub>] (1), [Fe(CO)<sub>2</sub>L<sub>PNN</sub>] (2), [Fe(CO)<sub>2</sub>L<sub>PNN</sub>](BF<sub>4</sub>) (3), [Fe(F)(CO)<sub>2</sub>L<sub>PNN</sub>](BF<sub>4</sub>) (4), and [Fe(H)(CO)<sub>2</sub>L<sub>PNN</sub>](BF<sub>4</sub>) (5) with formal oxidation states ranging from Fe(0) to Fe(II) (L<sub>PNN</sub> = 2-[(di-tert-butylphosphino)methyl]-6-[1-(2,4,6-mesitylimino)ethyl]pyridine). The complexes were characterized by a variety of methods including <sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>N, and <sup>31</sup>P NMR, IR, Mössbauer, and X-ray photoelectron spectroscopy (XPS) as well as electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy, SQUID magnetometry, and X-ray crystallography, focusing on the assignment of the metal oxidation states. Ligand structural features suggest that the α-iminopyridine ligand behaves as a redox non-innocent ligand in some of these complexes, particularly in [Fe(CO)<sub>2</sub>L<sub>PNN</sub>] (2), in which it appears to adopt the monoanionic form. In addition, the NMR spectroscopic features (<sup>13</sup>C, <sup>15</sup>N) indicate the accumulation of charge density on parts of the ligand for 2. However, a combination of spectroscopic measurements that more directly probe the iron oxidation state (e.g., XPS), density functional theory (DFT) calculations, and electronic absorption studies combined with time-dependent DFT calculations support the description of the metal atom in 2 as Fe(0). We conclude from our studies that ligand structural features, while useful in many assignments of ligand redox non-innocence, may not always accurately reflect the ligand charge state and, hence, the metal oxidation state. For complex 2, the ligand structural changes are interpreted in terms of strong back-donation from the metal center to the ligand as opposed to electron transfer. (Chemical Equation Presented).
Petkun S., Grinberg I. R., Lamed R., Jindou S., Burstein T., Yaniv O., Shoham Y., Shimon L. J. W., Bayer E. & Frolow F. (2015) PeerJ. 2015, 9, 1126
Non-cellulosomal processive endoglucanase 9I (Cel9I) from Clostridium thermocellum is a modular protein, consisting of a family-9 glycoside hydrolase (GH9) catalytic module and two family-3 carbohydrate-binding modules (CBM3c and CBM3b), separated by linker regions. GH9 does not show cellulase activity when expressed without CBM3c and CBM3b and the presence of the CBM3c was previously shown to be essential for endoglucanase activity. Physical reassociation of independently expressed GH9 and CBM3c modules (containing linker sequences) restored 60-70% of the intact Cel9I endocellulase activity. However, the mechanism responsible for recovery of activity remained unclear. In this work we independently expressed recombinant GH9 and CBM3c with and without their interconnecting linker in Escherichia coli. We crystallized and determined the molecular structure of the GH9/linker-CBM3c heterodimer at a resolution of 1.68 °A to understand the functional and structural importance of the mutual spatial orientation of the modules and the role of the interconnecting linker during their re-association. Enzyme activity assays and isothermal titration calorimetry were performed to study and compare the effect of the linker on the re-association. The results indicated that reassembly of the modules could also occur without the linker, albeit with only very low recovery of endoglucanase activity. We propose that the linker regions in the GH9/CBM3c endoglucanases are important for spatial organization and fixation of the modules into functional enzymes.
Zenkina O. V., Gidron O., Shimon L. J. W., Iron M. A. & van der Boom M. E. (2015) Chemistry (Weinheim an der Bergstrasse, Germany). 21, 45, p. 16113-16125
This contribution describes the reactivity of a zero-valent palladium phosphine complex with substrates that contain both an aryl halide moiety and an unsaturated carbon-carbon bond. Although η<sup>2</sup>-coordination of the metal center to a C=C or C≡C unit is kinetically favored, aryl halide bond activation is favored thermodynamically. These quantitative transformations proceed under mild reaction conditions in solution or in the solid state. Kinetic measurements indicate that formation of η<sup>2</sup>-coordination complexes are not nonproductive side-equilibria, but observable (and in several cases even isolated) intermediates en route to aryl halide bond cleavage. At the same time, DFT calculations show that the reaction with palladium may proceed through a dissociation-oxidative addition mechanism rather than through a haptotropic intramolecular process (i.e., ring walking). Furthermore, the transition state involves coordination of a third phosphine to the palladium center, which is lost during the oxidative addition as the C-halide bond is being broken. Interestingly, selective activation of aryl halides has been demonstrated by adding reactive aryl halides to the η<sup>2</sup>-coordination complexes. The product distribution can be controlled by the concentration of the reactants and/or the presence of excess phosphine.
Tulchinsky Y., Kozuch S., Saha P., Mauda A., Nisnevich G., Botoshansky M., Shimon L. J. & Gandelman M. (2015) Chemistry-A European Journal. 21, 19, p. 7099-7110
Comprehensive studies on the coordination properties of tridentate nitrenium-based ligands are presented. N-heterocyclic nitrenium ions demonstrate general and versatile binding abilities to various transition metals, as exemplified by the synthesis and characterization of Rh<sup>I</sup>, Rh<sup>III</sup>, Mo<sup>0</sup>, Ru<sup>0</sup>, Ru<sup>II</sup>, Pd<sup>II</sup>, Pt<sup>II</sup>, Pt<sup>IV</sup>, and Ag<sup>I</sup> complexes based on these unusual ligands. Formation of nitrenium-metal bonds is unambiguously confirmed both in solution by selective <sup>15</sup>N-labeling experiments and in the solid state by X-ray crystallography. The generality of N-heterocyclic nitrenium as a ligand is also validated by a systematic DFT study of its affinity towards all second-row transition and post-transition metals (Y-Cd) in terms of the corresponding bond-dissociation energies.
Gur D., Shimon L. J. & Parkin S. (2015) Acta crystallographica. Section E, Crystallographic communications. 71, 3, p. 281-283
In the title compound, disodium 2-amino-6-oxo-6,7-dihydro-1H-purine-1,7-diide heptahydrate, 2Na<sup>+</sup>·C<sub>5</sub>H<sub>3</sub>N<sub>5</sub>O<sup>2-</sup>·7H<sub>2</sub>O, the structure is composed of alternating (100) layers of guanine molecules and hydrated Na<sup>+</sup> ions. Within the guanine layer, the molecules are arranged in centrosymmetric pairs, with a partial overlap between the guanine rings. In this compound, guanine exists as the amino-keto tautomer from which deprotonation from N1 and N<sub>7</sub> has occurred (purine numbering). There are no direct interactions between the Na<sup>+</sup> cations and the guanine anions. Guanine molecules are linked to neighboring water molecules by O - H⋯N and O - H⋯O hydrogen bonds into a network structure.
Barats-Damatov D., Shimon L. J., Feldman Y., Bendikov T. & Neumann R. (2015) Inorganic Chemistry. 54, 2, p. 628-634
The crystal packing and secondary structure of H<sub>5</sub>PV<sub>2</sub>Mo<sub>12</sub>O<sub>40</sub> was followed by careful X-ray diffraction studies that revealed four unique structures and three solid phase transitions at temperatures between 25 and 55 °C, with loss of solvated water and concomitant contraction of the volume and increase of the packing density. Above 60 °C H<sub>5</sub>PV<sub>2</sub>Mo<sub>12</sub>O<sub>40</sub> becomes amorphous and then anhydrous although the polyoxometalate cluster is stable indefinitely up to 300 °C. Above this temperature, combined IR, Raman, XRD, and XPS measurements show the decomposition of H<sub>5</sub>PV<sub>2</sub>Mo<sub>12</sub>O<sub>40</sub> to crystalline MoO<sub>3</sub> and probably amorphous vanadium oxide and vanadylphosphate, the latter appearing to cover the surface of MoO<sub>3</sub>. Importantly, H<sub>5</sub>PV<sub>2</sub>Mo<sub>12</sub>O<sub>40</sub> can be easily recovered by dissolution in water at 80 °C.
Amar M., Bar S., Iron M. A., Toledo H., Tumanskii B., Shimon L. J., Botoshansky M., Fridman N. & Szpilman A. M. (2015) Nature Communications. 6, 6070
Stable nitroxides (nitroxyl radicals) have many essential and unique applications in chemistry, biology and medicine. However, the factors influencing their stability are still under investigation, and this hinders the design and development of new nitroxides. Nitroxides with tertiary alkyl groups are generally stable but obviously highly encumbered. In contrast, α -hydrogen-substituted nitroxides are generally inherently unstable and rapidly decompose. Herein, a novel, concept for the design of stable cyclic α -hydrogen nitroxides is described, and a proof-of-concept in the form of the facile synthesis and characterization of two diverse series of stable α -hydrogen nitroxides is presented. The stability of these unique α -hydrogen nitroxides is attributed to a combination of steric and stereoelectronic effects by which disproportionation is kinetically precluded. These stabilizing effects are achieved by the use of a nitroxide co-planar substituent in the Î 3-position of the backbone of the nitroxide. This premise is supported by a computational study, which provides insight into the disproportionation pathways of α -hydrogen nitroxides.
Balaraman E., Srimani D., Diskin Posner Y. & Milstein D. (2015) Catalysis Letters. 145, 1, p. 139-144
Efficient and selective direct synthesis of secondary amines from primary alcohols and ammonia with liberation of water has been achieved, with high turnover numbers and with no generation of waste. In case of benzylic alcohols, imines rather than amines are obtained. This atom economical, environmentally benign reaction is homogenously catalyzed by a well-defined bipyridine based Ru(II)-PNN pincer complex.
Orbach M., Shankar S., Zenkina O. V., Milko P., Diskin Posner Y. & van der Boom M. E. (2015) Organometallics. 34, 6, p. 1098-1106
This combined experimental and computational study demonstrates how a metal center can drastically influence the reactivity of a coordinated ligand. We found that the consecutive formation of zerovalent bimetallic complexes proceeds by fast n<sup>2</sup>-C - C coordination of only one Pd(PEt<sub>3</sub>)<sub>2</sub> moiety, which then significantly slows down the subsequent reaction. Electronic effects induced by complexation of the first metal center have a major effect on the subsequent formation of the bimetallic complexes. These effects are reduced by partial fluorination of the bis(vinylpyridine)-arene ligand. The monometallic complexes display migration of the Pd(PEt<sub>3</sub>)<sub>2</sub> moiety between the two olefinic bonds of the corresponding ligand, as indicated by various solution NMR experiments, including variable-temperature NMR spectroscopy, 2D <sup>1</sup>H-<sup>1</sup>H exchange spectroscopy, and spin saturation transfer. Density functional theory studies were performed at the SMD(toluene)-PBE0+d(v3)/B2//B97D/B1 level of theory.
Hu P., Fogler E., Diskin Posner Y., Iron M. A. & Milstein D. (2015) Nature Communications. 6, 6859
Hydrogen is an efficient green fuel, but its low energy density when stored under high pressure or cryogenically, and safety issues, presents significant disadvantages; hence finding efficient and safe hydrogen carriers is a major challenge. Of special interest are liquid organic hydrogen carriers (LOHCs), which can be readily loaded and unloaded with considerable amounts of hydrogen. However, disadvantages include high hydrogen pressure requirements, high reaction temperatures for both hydrogenation and dehydrogenation steps, which require different catalysts, and high LOHC cost. Here we present a readily reversible LOHC system based on catalytic peptide formation and hydrogenation, using an inexpensive, safe and abundant organic compound with high potential capacity to store and release hydrogen, applying the same catalyst for loading and unloading hydrogen under relatively mild conditions. Mechanistic insight of the catalytic reaction is provided. We believe that these findings may lead to the development of an inexpensive, safe and clean liquid hydrogen carrier system.
Amanchi S. R., Khenkin A. M., Diskin Posner Y. & Neumann R. (2015) ACS Catalysis. 5, 6, p. 3336-3341
The epoxidation of alkenes with peroxides by W<sup>VI</sup>, Mo<sup>VI</sup>, V<sup>V</sup>, and Ti<sup>IV</sup> compounds is well established, and it is well accepted that the active intermediate peroxo species are electrophilic toward nucleophilic substrates. Polyoxotungstates, for example, those of the "sandwich" structure, [WZn(TM-L)<sub>2</sub>(ZnW<sub>9</sub>O<sub>34</sub>)<sup>2</sup>]<sup>q-</sup> in which TM = transition metal and L = H<sub>2</sub>O, have in the past been found to be excellent epoxidation catalysts. It has now been found that substituting the Lewis basic Bi<sup>III</sup> into the terminal position of the "sandwich" polyoxometalate structure to yield [Zn<sub>2</sub>Bi<sup>III</sup><sub>2</sub>(ZnW<sub>9</sub>O<sub>34</sub>)<sub>2</sub>]<sup>14-</sup> leads to an apparent umpolung of the peroxo species and formation of a nucleophilic peroxo intermediate. There are two lines of evidence that support the formation of a reactive nucleophilic peroxo intermediate: (1) More electrophilic sulfoxides are more reactive than more nucleophilic sulfides, and (2) nonfunctionalized aliphatic alkenes and dienes showed ene type reactivity rather than epoxidation pointing toward "dark" formation of singlet oxygen from the nucleophilic intermediate peroxo species. Allylic alcohols reacted much faster than alkenes but showed chemoselectivity toward C-H bond activation of the alcohol and formation of aldehydes or ketones rather than epoxidation. This explained via alkoxide formation at the Bi<sup>III</sup> center followed by oxidative β-elimination.
Belitzky A., Weissbuch I., Posner-Diskin Y., Lahav M. & Lubomirsky I. (2015) Crystal Growth & Design. 15, 5, p. 2445-2451
As part of an ongoing program on the design of functional materials with a varying degree of polarity, we investigated the processes of conversion of a nonpolar host, l-asparagine monohydrate crystal (space group P2<sub>1</sub>2<sub>1</sub>2<sub>1</sub>), into a conglomerate of mixed polar sectors when grown in the presence of varying amounts of l-aspartic acid guest at the glass-aqueous/solution interface. The structure, composition, and the reduction of symmetry of the mixed crystals were confirmed with pyroelectric coefficient measurements, X-ray diffraction, and HPLC analysis and supported by atom-atom potential energy computations. The pyroelectricity measured at the (010) and (01¯0) faces imply the formation of hybrid crystals with top and bottom parts having opposite polarities. Pyroelectric coefficients measured at these two faces as a function of the occluded guest concentration increase linearly up to 8 wt %/wt of guest, followed by an enhancement of polarity at 8-12 wt %/wt of guest and subsequent reduction upon an increase up to 16 wt %/wt of guest. An interpretation of the magnitude of the pyroelectric effect on guest concentration is proposed.
Fogler E., Efremenko I., Gargir M., Leitus G., Diskin Posner Y., Ben-David Y., Martin J. M. L. & Milstein D. (2015) Inorganic Chemistry. 54, 5, p. 2253-2263
We report on Ru<sup>(II)</sup>(μ<sup>2</sup>-O<sub>2</sub>) nitrosyl pincer complexes that can return to their original Ru(0) state by reaction with mono-oxygen scavengers. Potential intermediates were calculated by density functional theory (DFT) and a mechanism is proposed, revealing a new type of metal-ligand cooperation consisting of activation of the O<sub>2</sub> moiety by both the metal center and the NO ligand. Reaction of the Ru(0) nitrosyl complex 1 with O<sub>2</sub> quantitatively yielded the crystallographically characterized Ru<sup>(II)</sup> (μ<sup>2</sup>-O<sub>2</sub>) nitrosyl complex 2. Reaction of 2 with the mono-oxygen scavengers phosphines or CO gave the Ru(0) complex 1 and phosphine oxides, or the carbonyl complex 3 (1 trapped by CO) and CO<sub>2</sub>, respectively. Reaction of 2 with 1 equiv of phosphine at room temperature or -40 °C resulted in immediate formation of half an equivalent of 1 and 1 equiv of phosphine oxide, while half an equivalent of 2 remained unchanged. Overnight reaction at room temperature of 2 with excess CO (≤3 equiv) resulted in 3 and CO<sub>2</sub> gas as the only products. Reaction of 1 with 1 equiv of mono-oxygen source (dioxirane) at -78 °C yielded the Ru<sup>(II)</sup>(μ<sup>2</sup>-O<sub>2</sub>) complex 2. Similarly, reaction of the Ru(0) dearomatized complex 4 with O<sub>2</sub> led to the crystallographicaly characterized Ru<sup>(II)</sup>(μ<sup>2</sup>-O<sub>2</sub>) complex 5. Further reaction of 5 with mono-oxygen scavengers (phosphines or CO) led to the Ru(0) complex 4 and phosphine oxides or complex 6 (4 trapped by CO) and CO<sub>2</sub>. When instead only 1 equiv of 5 was reacted with 1 equiv of phosphine at room temperature, immediate formation of half an equivalent of 4 and 1 equiv of phosphine oxide took place, while half an equivalent of 5 remained unchanged. When 5 reacted with an excess of CO (≤3 equiv), complex 6 and CO<sub>2</sub> gas were the only products obtained. DFT studies indicate a new mode of metal-ligand cooperation involving the nitrosyl ligand in the oxygen transfer process.
Rivada Wheelaghan O., Dauth A., Leitus G., Diskin Posner Y. & Milstein D. (2015) Inorganic Chemistry. 54, 9, p. 4526-4538
A novel pincer ligand based on the pyrazine backbone (PNzP) has been synthesized, (2,6-bis(di(tert-butyl)phosphinomethyl)pyrazine), tBu-PNzP. It reacts with FeBr<sub>2</sub> to yield [Fe(Br)<sub>2</sub>(tBu-PNzP)], 1. Treatment of 1 with NaBH<sub>4</sub> in MeCN/MeOH gives the hydride complex [Fe(H)(MeCN)<sub>2</sub>(tBu-PNzP)][X] (X = Br, BH<sub>4</sub>), 2·X. Counterion exchange and exposure to CO atmosphere yields the complex cis-[Fe(H)(CO)(MeCN)(tBu-PNzP)][BPh<sub>4</sub>] 4·BPh<sub>4</sub>, which upon addition of Bu<sub>4</sub>NCl forms [Fe(H)(Cl)(CO)(tBu-PNzP)] 5. Complex 5, under basic conditions, catalyzes the hydrogenation of CO<sub>2</sub> to formate salts at low H<sub>2</sub> pressure. Treatment of complex 5 with a base leads to aggregates, presumably of dearomatized species B, stabilized by bridging to another metal center by coordination of the nitrogen at the backbone of the pyrazine pincer ligand. Upon dissolution of compound B in EtOH the crystallographically characterized complex 7 is formed, comprised of six iron units forming a 6-membered ring. The dearomatized species can activate CO<sub>2</sub> and H<sub>2</sub> by metal-ligand cooperation (MLC), leading to complex 8, trans-[Fe(PNzPtBu-COO)(H)(CO)], and complex 9, trans-[Fe(H)<sub>2</sub>(CO)(tBu-PNzP)], respectively. Our results point at a very likely mechanism for CO<sub>2</sub> hydrogenation involving MLC.
Feller M., Ben-Ari E., Diskin Posner Y., Carmieli R., Weiner L. & Milstein D. (2015) Journal of the American Chemical Society. 137, 14, p. 4634-4637
A unique mode of molecular oxygen activation, involving metal-ligand cooperation, is described. Ir pincer complexes [(<sup>t</sup>BuPNP)Ir(R)] (R = C<sub>6</sub>H<sub>5</sub> (1), CH<sub>2</sub>COCH<sub>3</sub> (2)) react with O<sub>2</sub> to form the dearomatized hydroxo complexes [(<sup>t</sup>BuPNP∗)Ir(R)(OH)] (<sup>t</sup>BuPNP∗ = deprotonated <sup>t</sup>BuPNP ligand), in a process which utilizes both O-atoms. Experimental evidence, including NMR, EPR, and mass analyses, indicates a binuclear mechanism involving an O-atom transfer by a peroxo intermediate.
Fogler E., Garg J. A., Hu P., Leitus G., Shimon L. J. W. & Milstein D. (2014) Chemistry - A European Journal. 20, 48, p. 15727-15731
Metal-ligand cooperation (MLC) plays an important role in catalysis. Systems reported so far are generally based on a single mode of MLC. We report here a system with potential for MLC by both amine-amide and aromatization- dearomatization ligand transformations, based on a new class of phosphino-pyridyl ruthenium pincer complexes, bearing sec-amine coordination. These pincer complexes are effective catalysts under unprecedented mild conditions for acceptorless dehydrogenative coupling of alcohols to esters at 35 degrees C and hydrogenation of esters at room temperature and 5 atm H-2. The likely actual catalyst, a novel, crystallographically characterized monoanionic de-aromatized enamido-Ru-II complex, was obtained by deprotonation of both the N-H and the methylene proton of the N-arm of the pincer ligand.
Voronov-Goldman M., Levy-Assaraf M., Yaniv O., Wisserman G., Jindou S., Borovok I., Bayer E. A., Lamed R., Shimon L. J. & Frolow F. (2014) Acta Crystallographica Section F-Structural Biology Communications. 70, 4, p. 450-456
Ruminococcus flavefaciens is a cellulolytic bacterium found in the rumen of herbivores and produces one of the most elaborate and variable cellulosome systems. The structure of an R. flavefaciens protein (RfCohG, ZP06142108), representing a freestanding (non-cellulosomal) type III cohesin module, has been determined. A selenomethionine derivative with a C-terminal histidine tag was crystallized and diffraction data were measured to 2.44 Å resolution. Its structure was determined by single-wavelength anomalous dispersion, revealing eight molecules in the asymmetric unit. RfCohG exhibits the most complex among all known cohesin structures, possessing four -helical elements and a topographical protuberance on the putative dockerin-binding surface.
Anaby A., Butschke B., Ben-David Y., Shimon L. J. W., Leitus G., Feller M. & Milstein D. (2014) Organometallics. 33, 14, p. 3716-3726
Organic derivatives of boronic acid are widely used reagents useful in various synthetic applications. A fundamental understanding and the exploration of new reaction pathways of boronic reagents with organometallic systems hold promise for useful advancement in chemical catalysis. Herein we present the reactions of simple boranes with dearomatized ruthenium pincer complexes based on PNP (2,6-bis(di-tert-butylphosphinomethyl)pyridine) or PNN (2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine) ligands. NMR studies revealed dehydrogenative addition of the borane B-H bond across the metal center and the ligand. Remarkably, new complexes were observed, which contain the boryl moiety at the benzylic carbon of the pincer ligand arm. X-ray crystal structures of new dearomatized boryl pincer complexes were obtained, and DFT calculations revealed mechanistic details of the adduct formation process through a dehydrogenative pathway. In addition, catalytic aryl-boron coupling reactions were explored. The new boryl pincer systems may possibly be useful in future postmodification techniques for ruthenium pincer complexes, as well as in catalytic B-B and B-C coupling reactions.
Kulkarni N. V., Elkin T., Tumaniskii B., Botoshansky M., Shimon L. J. W. & Eisen M. S. (2014) Organometallics. 33, 12, p. 3119-3136
A series of asymmetric formamidine ligands bearing different substituents with various steric and electronic properties on the nitrogen of the N-C-N motif were synthesized. Group 4 bis(formamidinate) dimethylamido, chloride, and benzyl complexes were studied using these asymmetric ligands and their solid-state structures and their behavior in solution were determined. These complexes were activated with MAO (methylalumoxane) or a combination of cocatalysts and tested in the polymerization of ethylene and propylene. A noticeable influence of the formamidine nitrogen substituents on the activity of the catalyst and properties of the obtained polymers was observed. Further, a plausible mechanism for the polymerization of propylene is presented derived from a combination of ESR-C<sub>60</sub> and MALDI-TOF trapping experiments which shed light on the nature of the active catalytic species.
Tulchinsky Y., Kozuch S., Saha P., Botoshansky M., Shimon L. & Gandelman M. (2014) Chemical Science. 5, 4, p. 1305-1311
Nitrenium ligands provide an excellent platform for the straightforward and efficient synthesis of extremely rare complexes that possess positively charged ligands coordinated to positively charged metals. Examples of stable cation-cation and cation-dication coordination bonds are demonstrated. Computational studies show that such bonding is greatly stabilized by its incorporation into a tridentate frame, as well as the use of polar solvents.
Yaniv O., Fichman G., Borovok I., Shoham Y., Bayer E., Lamed R., Shimon L. & Frolow F. (2014) ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. 70, 2, p. 522-534
The anaerobic, thermophilic, cellulosome-producing bacterium Clostridium thermocellum relies on a variety of carbohydrate-active enzymes in order to efficiently break down complex carbohydrates into utilizable simple sugars. The regulation mechanism of the cellulosomal genes was unknown until recently, when genomic analysis revealed a set of putative operons in C. thermocellum that encode σ<sup>I</sup> factors (i.e. alternative σ factors that control specialized regulon activation) and their cognate anti- σ<sup>I</sup> factor (RsgI). These putative anti-σ<sup>I</sup>- factor proteins have modules that are believed to be carbohydrate sensors. Three of these modules were crystallized and their three-dimensional structures were solved. The structures show a high overall degree of sequence and structural similarity to the cellulosomal family 3 carbohydrate-binding modules (CBM3s). The structures of the three carbohydrate sensors (RsgI-CBM3s) and a reference CBM3 are compared in the context of the structural determinants for the specificity of cellulose and complex carbohydrate binding. Fine structural variations among the RsgI-CBM3s appear to result in alternative substrate preferences for each of the sensors.
Eckshtain-Levi M., Yufit D., Shimon L. J., Kirillov A. M. & Benisvy L. (2014) Crystal Growth & Design. 14, 6, p. 2703-2708
The design of multianionic chelating ligands as new organic linker for producing metal-organic frameworks (MOFs) is discussed. Three potentially polyanionic pro-ligands, 3,5-di-tert-butyl-2-hydroxy-N-(2-hydroxyethyl)benzamide (<sup>1</sup>LH<sub>3</sub>), bis(2-aminoethyl)-5-(tert-butyl)-2- hydroxyisophthalate (<sup>2a</sup>LH<sub>3</sub>), and 5-(tert-butyl)-2-hydroxy- N1,N3-bis(1-hydroxy-2-methylpropan-2-yl)isophthalamide (<sup>2b</sup>LH <sub>3</sub>), were synthesized and found to coordinate the osmyl ion in trianionic NO<sub>2</sub> fashion through the N-amidate, O-phenolate, and O-alcoholate donor atoms. The X-ray crystal structures of three dioxo-Os(VI) complexes: [Os<sub>2</sub>O<sub>4</sub>(<sup>1</sup>L)<sub>2</sub>(OH)K <sub>2</sub>(H<sub>2</sub>O)(C<sub>3</sub>H<sub>6</sub>O)] (Os<sup>1</sup>), [OsO<sub>2</sub>(<sup>2a</sup>L<sup>3-</sup>)(MeOH)<sub>4</sub>(MeO)K <sub>2</sub>] (Os<sup>2a</sup>), and [OsO<sub>2</sub>(<sup>2b</sup>L)(H <sub>2</sub>O)(C<sub>3</sub>H<sub>6</sub>O)K] (Os<sup>2b</sup>) reveal that the osmyl moiety and the ligand establish distinctive interactions with the potassium ions, yielding unprecedented infinite network from stepladder chain (in Os<sup>2b</sup>) and 2D-grid (in Os<sup>1</sup>) to 3D-porous H-bonding network (in Os<sup>2a</sup>).
Amir A., Ezra A., Shimon L. J. & Fischer B. (2014) Inorganic Chemistry. 53, 15, p. 7901-7908
Bis(dialkyl/aryl-phosphorothioyl)amide (BPA) derivatives are versatile ligands known by their high metal-ion affinity and selectivity. Here, we synthesized related chelators based on bis(1,3,2-dithia/dioxaphospholane-2- sulfide)amide (BTPA/BOPA) scaffolds targeting the chelation of soft metal ions. Crystal structures of BTPA compounds 6 (N<sup>-</sup>R<sub>3</sub>NH <sup>+</sup>) and 8 (NEt) revealed a gauche geometry, while BOPA compound 7 (N<sup>-</sup>R<sub>3</sub>NH<sup>+</sup>) exhibited an anti-geometry. Solid-state <sup>31</sup>P magic-angle spinning NMR spectra of BTPA 6-Hg(II) and 6-Zn(II) complexes imply a square planar or tetrahedral geometry of the former and a distorted tetrahedral geometry of the latter, while both BTPA 6-Ni(II) and BOPA 7-Ni(II) complexes possibly form a polymeric structure. In Cu(I)-H <sub>2</sub>O<sub>2</sub> system (Fenton reaction conditions) BTPA compounds 6, 8, and 10 (NCH<sub>2</sub>Ph) were identified as most potent antioxidants (IC<sub>50</sub> 32, 56, and 29 μM, respectively), whereas BOPA analogues 7, 9 (NEt), and 11 (NCH<sub>2</sub>Ph) were found to be poor antioxidants. In Fe(II)-H<sub>2</sub>O<sub>2</sub> system, IC<sub>50</sub> values for both BTPA and BOPA compounds exceeded 500 μM indicating high selectivity to Cu(I) versus the borderline Fe(II)-ion. Neither BTPA nor BOPA derivatives showed radical scavenging properties in H<sub>2</sub>O<sub>2</sub> photolysis, implying that inhibition of the Cu(I)-induced Fenton reaction by both BTPA and BOPA analogues occurred predominantly through Cu(I)-chelation. In addition, NMR-monitored Cu(I)- and Zn(II)-titration of BTPA compounds 8 and 10 showed their high selectivity to a soft metal ion, Cu(I), as compared to a borderline metal ion, Zn(II). In summary, lipophilic BTPA analogues are promising highly selective Cu(I) ion chelators.
Jin X. H., Sheberla D., Shimon L. J. & Bendikov M. (2014) Journal of the American Chemical Society. 136, 6, p. 2592-2601
Well-defined monodisperse conjugated oligomers, which have planar backbones and are free from the disturbance of substituents, attract broad interest. Herein, we report a series of symmetrical, isomerically pure oligofurans, namely, the 16-mer 16F-6C<sub>6</sub> together with the related nF-2C <sub>6</sub> (n = 4, 6, 8). Through computational studies and detailed spectroscopic and X-ray characterization, for the first time, we show that the planarity of the furan backbone is almost unaffected by the head-to-head defect which is known to cause considerable twists in its oligo- or polythiophene analogues. We present that the properties of these rigid oligo(alkylfuran)s are strongly influenced by the conjugation length. As the longest monodisperse α-oligofuran synthesized to date, 16F-6C<sub>6</sub> was observed to be stable and highly fluorescent. Experimental and computational studies of the redox states of these oligo(alkylfuran)s reveal that 16F-6C<sub>6</sub> has singlet biradical (polaron-pair) character in the doubly oxidized ground state: the open-shell singlet (〈S<sub>2</sub>〉 = 0.989) is 3.8 kcal/mol more stable than the closed-shell dication.
Barats-Damatov D., Shimon L. J., Weiner L., Schreiber R. E., Jiménez-Lozano P., Poblet J. M., De Graaf C. & Neumann R. (2014) Inorganic Chemistry. 53, 3, p. 1779-1787
High-valent oxo compounds of transition metals are often implicated as active species in oxygenation of hydrocarbons through carbon-hydrogen bond activation or oxygen transfer and also in water oxidation. Recently, several examples of cobalt-catalyzed water oxidation have been reported, and cobalt(IV) species have been suggested as active intermediates. A reactive species, formally a dicobalt(IV)-μ-oxo polyoxometalate compound [(α<sub>2</sub>- P<sub>2</sub>W<sub>17</sub>O<sub>61</sub>Co)<sub>2</sub>O]<sup>14-</sup>, [(POMCo)<sub>2</sub>O], has now been isolated and characterized by the oxidation of a monomeric [α<sub>2</sub>-P<sub>2</sub>W<sub>17</sub>O <sub>61</sub>Co<sup>II</sup>(H<sub>2</sub>O)]<sup>8-</sup>, [POMCo <sup>II</sup>H<sub>2</sub>O], with ozone in water. The crystal structure shows a nearly linear Co-O-Co moiety with a Co-O bond length of ∼1.77 Å. In aqueous solution [(POMCo)<sub>2</sub>O] was identified by <sup>31</sup>P NMR, Raman, and UV-vis spectroscopy. Reactivity studies showed that [(POMCo) <sub>2</sub>O]<sub>2</sub>O] is an active compound for the oxidation of H <sub>2</sub>O to O<sub>2</sub>, direct oxygen transfer to water-soluble sulfoxides and phosphines, indirect epoxidation of alkenes via a Mn porphyrin, and the selective oxidation of alcohols by carbon-hydrogen bond activation. The latter appears to occur via a hydrogen atom transfer mechanism. Density functional and CASSCF calculations strongly indicate that the electronic structure of [(POMCo)<sub>2</sub>O]<sub>2</sub>O] is best defined as a compound having two cobalt(III) atoms with two oxidized oxygen atoms.
Vogt M., Nerush A., Diskin Posner Y., Ben David Y. & Milstein D. (2014) Chemical Science. 5, 5, p. 2043-2051
Herein we report the reversible binding of CO<sub>2</sub> to a very rare dearomatized PNP pincer complex (cis-[Re(PNP<sup>tBu</sup>*)(CO) <sub>2</sub>] 2). The [1,3]-addition of CO<sub>2</sub> to the pincer complex is triggered by metal-ligand cooperation via an aromatization/dearomatization sequence to form cis-[Re(PNP<sup>tBu</sup>-COO)(CO)<sub>2</sub>] (3) via Re-O and C-C bond formation. The reversible binding was demonstrated by the exchange reaction of <sup>13</sup>CO<sub>2</sub>/CO<sub>2</sub> from the isotopically labelled compound cis-[Re(PNP<sup>tBu</sup>-<sup>13</sup>COO)(CO)<sub>2</sub>] (3a). Furthermore, complex 3 reacts with H<sub>2</sub> to give free CO <sub>2</sub> and the aromatized hydride complex cis-[Re(PNP<sup>tBu</sup>)(CO) <sub>2</sub>H] (4), which undergoes the reverse reaction to re-form 3 under CO<sub>2</sub> pressure at elevated temperature. Alternatively, 4 reacts, in a low temperature pathway, via the insertion of CO<sub>2</sub> into the Re-H bond to give the formate complex cis-[Re(PNP<sup>tBu</sup>)(CO)<sub>2</sub>(OOCH)] (5)]. Remarkably, complex 5 catalyses efficiently the dehydrogenation of formic acid under base-free conditions.
Hu P., Diskin Posner Y., Ben-David Y. & Milstein D. (2014) ACS Catalysis. 4, 8, p. 2649-2652
An efficient system catalyzed by a Ru-PNN pincer complex was developed for reforming methanol to H<sub>2</sub> and CO<sub>2</sub> (absorbed by base) under relatively low temperature (around 100 °C), and good yields of H<sub>2</sub> were obtained (∼80%). The catalyst solution can be reused without isolation and purification, with no decrease in catalytic activity being observed for a period of ∼1 month. Decomposition of formic acid, which is likely to be the last step of the methanol reforming reaction, was also investigated, and the formic acid adduct of the catalyst was fully characterized spectroscopically and by X-ray crystallography.
Zell T., Milko P., Fillman K. L., Diskin Posner Y., Bendikov T., Iron M. A., Leitus G., Ben-David Y., Neidig M. L. & Milstein D. (2014) Chemistry - A European Journal. 20, 15, p. 4403-4413
A series of iron dicarbonyl complexes with bipyridine-based PNN pincer ligands were synthesized and characterized by multinuclear NMR spectroscopy (<sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>N, <sup>31</sup>P), IR spectroscopy, cyclic voltammetry, <sup>57</sup>Fe Mössbauer spectroscopy, XPS spectroscopy, and single-crystal X-ray diffraction. The complexes with the general formula [(R-PNN)Fe(CO)<sub>2</sub>] (5: R-PNN=tBu-PNN=6-[(di-tert- butylphosphino)methyl]-2,2-bipyridine, 6: R-PNN=iPr-PNN=6- [(diisopropylphosphino)methyl]-2,2-bipyridine, and 7: R-PNN=Ph-PNN=6-[(diphenylphosphino)methyl]-2,2-bipyridine) feature differently P-substituted PNN pincer ligands. Complexes 5 and 6 were obtained by reduction of the corresponding dihalide complexes [(R-PNN)Fe(X)<sub>2</sub>] (1: R=tBu, X=Cl; 2: R=tBu, X=Br; 3: R=iPr, X=Cl; 4: R=iPr, X=Br) in the presence of CO. The analogous Ph-substituted complex 7 was synthesized by a reaction of the free ligand with iron pentacarbonyl. The low-spin complexes 5-7 (S=0) are diamagnetic and have distorted trigonal bipyramidal structures in solution, whereas in the solid state the geometries around the iron are best described as distorted square pyramidal. Compared to other structurally characterized complexes with these PNN ligands, shortened interpyridine C-C bonds of about 1.43 Å were measured. A comparison with known examples, theoretically described as metal complexes bearing bipyridine π-radical anions (bpy <sup>.-</sup>), suggests that the complexes can be described as Fe<sup>I</sup> complexes with one electron antiferromagnetically coupled to the ligand-based radical anions. However, computational studies, at the NEVPT2/CASSCF level of theory, reveal that the shortening of the C-C bond is a result of extensive π-backbonding of the iron center into the antibonding orbital of the bpy unit. Hence, the description of the complexes as Fe <sup>0</sup> complexes with neutral bipyridine units is the favorable one. Innocent till proved guilty! Metrical parameters for the assignment of oxidation states of bipyridine ligands are challenged. A series of iron dicarbonyl complexes with bipyridine-based PNN pincer ligands were synthesized and fully characterized by various methods. Unusually short interpyridine C-C bonds were derived by X-ray diffraction (see scheme). The question if this is an effect of an intramolecular electron transfer or an effect of classical π-backbonding is addressed.
Vogt M., Rivada Wheelaghan O., Iron M. A., Leitus G., Diskin Posner Y., Shimon L. J. W., Ben-David Y. & Milstein D. (2013) Organometallics. 32, 1, p. 300-308
The aromatization-dearomatization reaction of pincer-type complexes prompted by protonation-deprotonation of the pincer "arm" is a key step in bond activation chemistry and atom-economic catalytic transformations. However, the possibility of double deprotonation of ancillary pincer ligands is rarely discussed in the literature. Here we report on square-planar cationic nickel(II) complexes of PNP<sup>R</sup> type ligands (PNP = 2,6- bis[(dialkylphosphino)methyl]pyridine with R = <sup>i</sup>Pr, <sup>t</sup>Bu), which can be readily transformed into the doubly deprotonated anionic species. The complexes [Ni(PNP<sup>R</sup>)Cl]Cl (3, R = <sup>i</sup>Pr; 4, R = <sup>t</sup>Bu) are readily prepared from the reaction of NiCl <sub>2</sub>·6H<sub>2</sub>O and the PNP<sup>R</sup> ligand in THF. Treatment of the cationic chloro complexes 3 and 4 with 2 equiv of MeLi gives the nickel(II) methyl complexes [Ni(PNP<sup>R</sup>*)Me] (7, R = <sup>i</sup>Pr; 8, R = <sup>t</sup>Bu), the asterisk indicates the deprotonated pincer arm). Reaction of 7 and 8 with an additional 1 equiv of MeLi gives the anionic complexes [Li(DME)<sub>3</sub>][Ni(PNP<sup>iPr</sup>**)Me] (9-DME, DME = 1,2-dimethoxyethane) and [Li(Et<sub>2</sub>O)<sub>2</sub>] [Ni(PNP<sup>tBu</sup>**)(Me)] (10-Et<sub>2</sub>O), respectively. Single-crystal X-ray diffraction studies exhibit doubly deprotonated PNP-pincer ligands coordinated to a nickel(II) center. DFT calculations, as well as multinuclear NMR spectroscopy and the X-ray structures, suggest a conjugated π-system with delocalization of the negative charge throughout the carbon backbone of the pincer ligand. The electrophilic attack of complex 9 by CO <sub>2</sub> and tautomerization gives [Li][Ni(PNP<sup>iPr</sup>*-COO)(Me) ] (11). The dearomatized complex that is formed contains an exocyclic methylene carbon atom and a carboxylate moiety adjacent to the second pincer arm.
Yaniv O., Morag E., Borovok I., Bayer E. A., Lamed R., Frolow F. & Shimon L. J. (2013) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 69, 7, p. 733-737
The cellulosome of the cellulolytic bacterium Clostridium thermocellum has a structural multi-modular protein called CipA (cellulosome-integrating protein A) that includes nine enzyme-binding cohesin modules and a family 3 cellulose-binding module (CBM3a). In the CipA protein, the CBM3a module is located between the second and third cohesin modules and is connected to them via proline/threonine-rich linkers. The structure of CBM3a with portions of the C- and N-terminal flanking linker regions, CBM3a-L, has been determined to a resolution of 1.98 Å. The structure is a β-sandwich with a structural Ca<sup>2+</sup> ion. The structure is consistent with the previously determined CipA CBM structure; however, the structured linker regions provide a deeper insight into the overall cellulosome structure and assembly.
Vogt M., Nerush A., Iron M. A., Leitus G., Diskin Posner Y., Shimon L. J. W., Ben-David Y. & Milstein D. (2013) Journal of the American Chemical Society. 135, 45, p. 17004-17018
The dearomatized complex cis-[Re(PNP<sup>tBu</sup>*)(CO)<sub>2</sub>] (4) undergoes cooperative activation of Cî - N triple bonds of nitriles via [1,3]-addition. Reversible C-C and Re-N bond formation in 4 was investigated in a combined experimental and computational study. The reversible formation of the ketimido complexes (5-7) was observed. When nitriles bearing an alpha methylene group are used, reversible formation of the enamido complexes (8 and 9) takes place. The reversibility of the activation of the nitriles in the resulting ketimido compounds was demonstrated by the displacement of p-CF <sub>3</sub>-benzonitrile from cis-[Re(PNP<sup>tBu</sup>-N=CPh <sup>pCF3</sup>)(CO)<sub>2</sub>] (6) upon addition of an excess of benzonitrile and by the temperature-dependent [1,3]-addition of pivalonitrile to complex 4. The reversible binding of the nitrile in the enamido compound cis-[Re(PNP <sup>tBu</sup>-HNC=CHPh)(CO)<sub>2</sub>] (9) was demonstrated via the displacement of benzyl cyanide from 9 by CO. Computational studies suggest a stepwise activation of the nitriles by 4, with remarkably low activation barriers, involving precoordination of the nitrile group to the Re(I) center. The enamido complex 9 reacts via β-carbon methylation to give the primary imino complex cis-[Re(PNP<sup>tBu</sup>-HN=CC(Me)Ph)(CO)<sub>2</sub>]OTf 11. Upon deprotonation of 11 and subsequent addition of benzyl cyanide, complex 9 is regenerated and the monomethylation product 2-phenylpropanenitrile is released. Complexes 4 and 9 were found to catalyze the Michael addition of benzyl cyanide derivatives to α,β-unsaturated esters and carbonyls.
Zell T., Langer R., Iron M. A., Konstantinovski L., Shimon L. J. W., Diskin Posner Y., Leitus G., Balaraman E., Ben-David Y. & Milstein D. (2013) Inorganic Chemistry. 52, 16, p. 9636-9649
The synthesis and characterization of new iron pincer complexes bearing bipyridine-based PNN ligands is reported. Three phosphine-substituted pincer ligands, namely, the known <sup>t</sup>Bu-PNN (6-((di-tert-butylphosphino) methyl)-2,2-bipyridine) and the two new <sup>i</sup>Pr-PNN (6-((di-iso-propylphosphino)methyl)-2,2-bipyridine) and Ph-PNN (6-((diphenylphosphino)methyl)-2,2-bipyridine) ligands were synthesized and studied in ligation reactions with iron(II) chloride and bromide. These reactions lead to the formation of two types of complexes: mono-chelated neutral complexes of the type [(R-PNN)Fe(X)<sub>2</sub>] and bis-chelated dicationic complexes of the type [(R-PNN)<sub>2</sub>Fe]<sup>2+</sup>. The complexes [(R-PNN)Fe(X)<sub>2</sub>] (1: R = <sup>t</sup>Bu, X = Cl, 2: R = <sup>t</sup>Bu, X = Br, 3: R = <sup>i</sup>Pr, X = Cl, and 4: R = <sup>i</sup>Pr, X = Br) are readily prepared from reactions of FeX<sub>2</sub> with the free R-PNN ligand in a 1:1 ratio. Magnetic susceptibility measurements show that these complexes have a high-spin ground state (S = 2) at room temperature. Employing a 2-fold or higher excess of <sup>i</sup>Pr-PNN, diamagnetic hexacoordinated dicationic complexes of the type [( <sup>i</sup>Pr-PNN)<sub>2</sub>Fe](X)<sub>2</sub> (5: X = Cl, and 6: X = Br) are formed. The reactions of Ph-PNN with FeX<sub>2</sub> in a 1:1 ratio lead to similar complexes of the type [(Ph-PNN)<sub>2</sub>Fe](FeX<sub>4</sub>) (7: X = Cl, and 8: X = Br). Single crystal X-ray studies of 1, 2, 4, 6, and 8 do not indicate electron transfer from the Fe<sup>II</sup> centers to the neutral bipyridine unit based on the determined bond lengths. Density functional theory (DFT) calculations were performed to compare the relative energies of the mono-and bis-chelated complexes. The doubly deprotonated complexes [(R-PNN*)<sub>2</sub>Fe] (9: R = <sup>i</sup>Pr, and 10: R = Ph) were synthesized by reactions of the dicationic complexes 6 and 8 with KO <sup>t</sup>Bu. The dearomatized nature of the central pyridine of the pincer ligand was established by X-ray diffraction analysis of single crystals of 10. Reactivity studies show that 9 and 10 have a slightly different behavior in protonation reactions.
Gidron O., Dadvand A., Wei-Hsin Sun E., Chung I., Shimon L. J., Bendikov M. & Perepichka D. F. (2013) Journal of Materials Chemistry C. 1, 28, p. 4358-4367
We describe the synthesis, characterization and field effect transistor (FET) properties of a series of furan-based conjugated oligomers such as unsubstituted, hexyl- and styryl-capped linear oligofurans and oligofuran-substituted anthracene derivatives. All studied oligofurans show high fluorescence and good thermal stability. Top contact organic FETs (OFETs) fabricated with oligofurans as the active layer show hole mobilities (∼0.01 to 0.07 cm<sup>2</sup> V<sup>-1</sup> s<sup>-1</sup>) and on/off ratios (10 <sup>4</sup> to 10<sup>6</sup>) on a par with the corresponding oligothiophene analogues, while the threshold voltages displayed by oligofuran-based OFETs are significantly reduced due to higher HOMO energies as compared to those of oligothiophenes. Electroluminescence observed in oligofuran-based OFETs in a bottom-contact geometry is limited by electron injection. Overall, we find that furan building blocks are excellent candidates for replacing thiophene in optoelectronic materials.
Fogler E., Iron M. A., Zhang J., Ben-David Y., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2013) Inorganic Chemistry. 52, 19, p. 11469-11479
Despite considerable interest in ruthenium carbonyl pincer complexes and their substantial catalytic activity, there has been relatively little study of the isoelectronic ruthenium nitrosyl complexes. Here we describe the synthesis and reactivity of several complexes of this type as well as the catalytic activity of complex 6. Reaction of the PNP ligand (PNP = 2,6-bis( <sup>t</sup>Bu<sub>2</sub>PCH<sub>2</sub>)pyridine) with RuCl <sub>3</sub>(NO)(PPh<sub>3</sub>)<sub>2</sub> yielded the Ru(II) complex 3. Chloride displacement by BAr<sup>F-</sup> (BAr<sup>F-</sup> = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) gave the crystallographicaly characterized, linear NO Ru(II) complex 4, which upon treatment with NaBEt <sub>3</sub>H yielded the Ru(0) complexes 5. The crystallographically characterized Ru(0) square planar complex 5·BF<sub>4</sub> bears a linear NO ligand located trans to the pyridilic nitrogen. Further treatment of 5·BF<sub>4</sub> with excess LiOH gave the crystallographicaly characterized Ru(0) square planar, linear NO complex 6. Complex 6 catalyzes the dehydrogenative coupling of alcohols to esters, reaching full conversion under air or under argon. Reaction of the PNN ligand (PNN = 2-(<sup>t</sup>Bu <sub>2</sub>PCH<sub>2</sub>)-6-(Et<sub>2</sub>NCH<sub>2</sub>)pyridine) with RuCl<sub>3</sub>(NO)(H<sub>2</sub>O)<sub>2</sub> in ethanol gave an equilibrium mixture of isomers 7a and 7b. Further treatment of 7a + 7b with 2 equivalent of sodium isopropoxide gave the crystallographicaly characterized, bent-nitrosyl, square pyramidal Ru(II) complex 8. Complex 8 was also synthesized by reaction of PNN with RuCl<sub>3</sub>(NO)(H<sub>2</sub>O)<sub>2</sub> and Et<sub>3</sub>N in ethanol. Reaction of the "long arm" PN<sup>2</sup>N ligand (PN <sup>2</sup>N = 2-(<sup>t</sup>Bu<sub>2</sub>PCH<sub>2</sub>-)-6-(Et <sub>2</sub>NCH<sub>2</sub>CH<sub>2</sub>)pyridine) with RuCl <sub>3</sub>(NO)(H<sub>2</sub>O)<sub>2</sub> in ethanol gave complex 9, which upon treatment with 2 equiv of sodium isopropoxide gave complex 10. Complex 10 was also synthesized directly by reaction of PN<sup>2</sup>N with RuCl <sub>3</sub>(NO)(H<sub>2</sub>O)<sub>2</sub> and a base in ethanol. A noteworthy aspect of these nitrosyl complexes is their preference for the Ru(0) oxidization state over Ru(II). This preference is observed with both aromatized and dearomatized pincer ligands, in contrast to the Ru(II) oxidation state which is preferred by the analogous carbonyl complexes.
Langer R., Fuchs I., Vogt M., Balaraman E., Diskin Posner Y., Shimon L. J. W., Ben-David Y. & Milstein D. (2013) Chemistry - A European Journal. 19, 10, p. 3407-3414
The synthesis and reactivity of ruthenium complexes containing the tetradentate phenanthroline-based phosphine ligand 2,9-bis((di-tert- butylphosphino)methyl)-1,10-phenanthroline (PPhenP) is described. The hydrido chloro complex [RuHCl(PPhenP)] (2) undergoes facile dearomatization upon deprotonation of the benzylic position, to give [RuH(PPhenP-H)] (4). Addition of dihydrogen to 4 causes rearomatization of the phenanthroline moiety to trans-[Ru(H)<sub>2</sub>(PPhenP)] (5), followed by hydrogenation of an aromatic heterocycle in the ligand backbone, to give a new dearomatized and deconjugated complex [RuH(PPhenP*-H)] (6). These aromatization/deconjugation steps of the coordinated ligand were demonstrated to be reversible and operative in the dehydrogenation of primary alcohols without the need for a hydrogen acceptor. This aromatization/deconjugation sequence constitutes an unprecedented mode of a stepwise cooperation between the metal center and the coordinated ligand. Obligation to cooperate: A dearomatization/deconjugation sequence, involving reversible hydrogenation of the ligand backbone, has been uncovered for the dihydrogen activation by ruthenium complexes with a tetradentate phenanthroline-based ligand. This unprecedented mode of stepwise cooperation between the metal center and the coordinated ligand is demonstrated to be reversible and operative in the dehydrogenation of primary alcohols without the need for a hydrogen acceptor (see scheme).
Maayan G., Dayagi Y., Arad-Yellin R., Shimon L. J. & Shanzer A. (2013) Polyhedron. 64, p. 365-370
The complexes of cobalt, copper and nickel ions with the known tridentate ligand 2-(2-pyridyl)-8-hydroxyquinoline (HQP) were prepared and characterized. The structures of the complexes with Co(II), Cu(II) and Ni(III) were corroborated by crystal structure analyses. The structures of the complexes with Co(III) and Cu(I) were realized from NMR measurements in solution. It was found that HQP stabilizes high oxidation states of the complexed metal ions. The results also suggest that HQP binds Cu(II) and Cu(I) in two different modes; Cu(II) forms an octahedral complex with the three elements of the ligand, namely, the 8-hydroxyl the two nitrogens of bipyridine, while Cu(I) binds only to two nitrogens of the bipyridine, yielding a tetra-coordinated complex.
Levy-Assaraf M., Voronov-Goldman M., Rozman Grinberg I., Weiserman G., Shimon L. J., Jindou S., Borovok I., White B. A., Bayer E. A., Lamed R. & Frolow F. (2013) PLoS ONE. 8, 2, e56138
Background: Ruminococcus flavefaciens is one of the predominant fiber-degrading bacteria found in the rumen of herbivores. Bioinformatic analysis of the recently sequenced genome indicated that this bacterium produces one of the most intricate cellulosome systems known to date. A distinct ORF, encoding for a multi-modular protein, RflaF_05439, was discovered during mining of the genome sequence. It is composed of two tandem modules of currently undefined function that share 45% identity and a C-terminal X-dockerin modular dyad. Gaining insight into the diversity, architecture and organization of different types of proteins in the cellulosome system is essential for broadening our understanding of a multi-enzyme complex, considered to be one of the most efficient systems for plant cell wall polysaccharide degradation in nature. Methodology/Principal Findings: Following bioinformatic analysis, the second tandem module of RflaF_05439 was cloned and its selenium-labeled derivative was expressed and crystallized. The crystals belong to space group P2<sub>1</sub> with unit-cell parameters of a = 65.81, b = 60.61, c = 66.13 Å, β = 107.66° and contain two protein molecules in the asymmetric unit. The crystal structure was determined at 1.38-Å resolution by X-ray diffraction using the single-wavelength anomalous dispersion (SAD) method and was refined to R<sub>factor</sub> and R<sub>free</sub> of 0.127 and 0.152 respectively. The protein molecule mainly comprises a β-sheet flanked by short α-helixes, and a globular α-helical domain. The structure was found to be structurally similar to members of the NlpC/P60 superfamily of cysteine peptidases. Conclusions/Significance: The 3D structure of the second repeat of the RflaF_05439 enabled us to propose a role for the currently undefined function of this protein. Its putative function as a cysteine peptidase is inferred from in silico structural homology studies. It is therefore apparent that cellulosomes integrate proteins with other functions in addition to the classic well-defined carbohydrate active enzymes.
Salama-Alber O., Jobby M. K., Chitayat S., Smith S. P., White B. A., Shimon L. J., Lamed R., Frolow F. & Bayer E. A. (2013) Journal of Biological Chemistry. 288, 23, p. 16827-16838
The rumen bacterium Ruminococcus flavefaciens produces a highly organized multienzyme cellulosome complex that plays a key role in the degradation of plant cell wall polysaccharides, notably cellulose. The R. flavefaciens cellulosomal system is anchored to the bacterial cell wall through a relatively small ScaE scaffoldin subunit, which bears a single type IIIe cohesin responsible for the attachment of two major dockerin-containing scaffoldin proteins, ScaB and the cellulose-binding protein CttA. Although ScaB recruits the catalytic machinery onto the complex, CttA mediates attachment of the bacterial substrate via its two putative carbohydrate-binding modules. In an effort to understand the structural basis for assembly and cell surface attachment of the cellulosome in R. flavefaciens, we determined the crystal structure of the high affinity complex (K<sub>d</sub> = 20.83 nM) between the cohesin module of ScaE (CohE) and its cognate X-dockerin (XDoc) modular dyad from CttA at 1.97-Å resolution. The structure reveals an atypical calcium-binding loop containing a 13-residue insert. The results further pinpoint two charged specificity-related residues on the surface of the cohesin module that are responsible for specific versus promiscuous cross-strain binding of the dockerin module. In addition, a combined functional role for the three enigmatic dockerin inserts was established whereby these extraneous segments serve as structural buttresses that reinforce the stalklike conformation of the X-module, thus segregating its tethered complement of cellulosomal components from the cell surface. The novel structure of the RfCohE-XDoc complex sheds light on divergent dockerin structure and function and provides insight into the specificity features of the type IIIe cohesin-dockerin interaction.
Gidron O., Varsano N., Shimon L. J., Leitus G. & Bendikov M. (2013) Chemical Communications. 49, 56, p. 6256-6258
A comparative study of two structural isomers highlights the advantages of bifuran vs. bithiophene units in conjugated systems, such as higher fluorescence, solubility, and increased stability of the oxidized species. Importantly, we have found that the small bifuran unit bestows the advantages found in longer oligofurans, and should be considered in the rational design of π-conjugated systems.
Feller M., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2013) Journal of the American Chemical Society. 135, 30, p. 11040-11047
Rare cases of directly observed reductive elimination (RE) of methyl halides from Rh<sup>III</sup> complexes are described. Treatment of the coordinatively unsaturated complexes [(<sup>t</sup>BuPNP)Rh(CH <sub>3</sub>)X][BF<sub>4</sub>] (1-3, X = I, Br, and Cl; <sup>t</sup>BuPNP = 2,6-bis-(di-tert-butylphosphinomethyl)pyridine) with coordinating and noncoordinating compounds results in the formation of the corresponding free methyl halides and Rh<sup>I</sup> complexes. The rate increase of CH <sub>3</sub>I and CH<sub>3</sub>Br RE in the presence of polar aprotic solvents argues in favor of an S<sub>N</sub>2 RE mechanism. However, the RE of CH <sub>3</sub>Cl is faster in polar protic solvents, which argues in favor of a concerted C-Cl RE. The RE of methyl halides from complexes 1-3 is induced by steric factors, as treatment of the less bulky complexes [(<sup>i</sup>PrPNP) Rh(CH<sub>3</sub>)X][BF<sub>4</sub>] (19-21; X = I, Br, Cl, respectively) with coordinating compounds leads to the formation of the adducts complexes rather than RE of the methyl halides. The accumulated evidence suggests that the RE process is nonassociative.
Barats-Damatov D., Shimon L. J. & Neumann R. (2013) European Journal of Inorganic Chemistry. 10-11, p. 1649-1653
Crystallization of the {HW<sub>9</sub>O<sub>33</sub>} isopolyanion in the presence of M<sup>II</sup>(DMSO)<sub>4</sub>Cl<sub>2</sub> (where M = Ru, Os) and Na and K cations yielded one-dimensional chains, {K[HW<sub>9</sub>O <sub>33</sub>M<sub>2</sub>(C<sub>2</sub>H<sub>6</sub>SO)<sub>6</sub>] <sup>6-</sup>}<sub>n</sub>. The {HW<sub>9</sub>O<sub>33</sub>} isopolyanion is capped by M<sup>II</sup>(DMSO)<sub>3</sub> moieties, which are, in turn, linked by potassium cations. The chains for the Ru<sup>II</sup>-based compound show a prismatic coordination around the K<sup>+</sup> linker and {HW<sub>9</sub>O <sub>33</sub>} moieties that are eclipsed relative to each other along the chain, while the Os<sup>II</sup>-based compound has an octahedral coordination around the K<sup>+</sup> linker and {HW<sub>9</sub>O<sub>33</sub>} moieties that are staggered relative to each other along the chain. The three-dimensional arrangement of the two compounds is quite different. For the Ru<sup>II</sup> compound, channels are obtained by the arrangement of six {K[HW <sub>9</sub>O<sub>33</sub>Ru<sub>2</sub>(C<sub>2</sub>H<sub>6</sub>SO) <sub>6</sub>]<sup>6-</sup>}<sub>n</sub> chains along the c axis. The channel is stabilized by the binding of sodium cations, which interlock the chains through coordination of different oxygen atoms and leads to a tight staggered arrangement between the chains of {K[HW<sub>9</sub>O<sub>33</sub>Ru <sub>2</sub>(C<sub>2</sub>H<sub>6</sub>SO)<sub>6</sub>]<sup>6-</sup>} <sub>n</sub>. The channels have an approximate diameter of 8 Å and are occupied by layers of six sodium cations that form chair-like hexagons with Na-Na interatomic distances of 2.807 Å. There are five water molecules that separate the layers of the Na<sup>+</sup> cations. For the osmium compound, two different types of channels, defined by the arrangement three {K[HW <sub>9</sub>O<sub>33</sub>Os<sub>2</sub>(C<sub>2</sub>H<sub>6</sub>SO) <sub>6</sub>]<sup>6-</sup>}<sub>n</sub> chains, are formed. The channels are formed through interchain bonding through a bridge formed by connecting sodium atoms to the terminal atoms of the {HW<sub>9</sub>O<sub>33</sub>} unit. Here, the {K[HW<sub>9</sub>O<sub>33</sub>Os<sub>2</sub>(C<sub>2</sub>H <sub>6</sub>SO)<sub>6</sub>]<sup>6-</sup>}<sub>n</sub> chains are eclipsed relative to one another. Water molecules occupy one channel, while the other channel is occupied by K<sup>+</sup> cations hexacoordinated to aqua ligands. The approximate diameter of the channels is 5.5 Å.
Barrios Francisco R., Balaraman E., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2013) Organometallics. 32, 10, p. 2973-2982
The synthesis of novel PNN ruthenium pincer complexes based on 2,2-dipyridinemethane phosphine derivatives, as well as on 2,2-oxobispyridine phosphine ligands, and their reactivity toward dearomatization and cyclometalation are described. The dearomatized compounds 7a,b undergo cyclometalation to yield complexes 8a,b. In order for cyclometalation to proceed, the coordination sphere around the Ru center has to rearrange, and this depends on the flexibility of the system, showing that the cyclometalation is qualitatively faster in the case of the dimethyl derivative 7a than in the case of the spyrocyclopentyl derivative 7b. The cyclometalation occurs diastereoselectively and leads to only one diastereomer of the cyclometalated compounds. In the case of the 2,2-oxobispyridine complex 6c, the dearomatized complex was too unstable to be isolated; however it was possible to isolate and characterize a stable dicarbonyl-dearomatized ruthenium(II) complex, 9c, when the deprotonation was performed under a CO atmosphere. Dearomatization of 6a under CO also led to dicarbonyl-dearomatized ruthenium(II) complex 9a, which slowly rearranged into the dicarbonyl-aromatized ruthenium(0) complex 10a. These complexes were tested in catalytic alcohol-amine coupling, esterification of primary alcohols, and hydrogenation of secondary amides. Moderate activity was observed in hydrogenation of amides to alcohols and amines and low activity in the other transformations, owing mainly to the formation of stable cyclometalated compounds.
Amir A., Sayer A. H., Zagalsky R., Shimon L. J. & Fischer B. (2013) Journal of Organic Chemistry. 78, 2, p. 270-277
A new transformation of methylene-bis(phosphonic dichloride) into tetrathiobisphosphonate derivatives is reported. The reaction of methylene-bis(phosphonic dichloride) with 1,2-ethanedithiol in bromoform in the presence of AlCl<sub>3</sub> formed methylene-bis(1,3,2-dithiaphospholane-2- sulfide), which gave rise to O,O-diester-methylenediphosphonotetrathioate analogues 1a-k upon reaction with phenols and alkyl alcohols in the presence of DBU. Reaction mechanisms are proposed, and all products were characterized by <sup>31</sup>P, <sup>13</sup>C, and <sup>1</sup>H NMR. An X-ray crystal structure was obtained for intermediate 2. The potential of the novel scaffold for selective coordination of metal-ions was examined by coordination of Hg(II) and Pb(II) by 1f, as determined by FT-IR, and chelation of Zn(II), but not Ca(II), by 1b, as determined by <sup>31</sup>P/<sup>1</sup>H NMR. UV-vis measurements of 1g-Ni(II) mixture revealed a 2:1 ligand:metal complex. These derivatives are potential antioxidants, and their ability to inhibit ·OH formation in Fenton reactions was quantified by ESR measurements. Analogue 1g proved to be a most potent antioxidant (IC<sub>50</sub> 53 μM), inhibiting the Cu(I)-catalyzed Fenton reaction at lower concentrations than GSH, ascorbic acid, and EDTA. Analogue 1c inhibited the Fe(II)-catalyzed Fenton reaction at about the same concentrations as ascorbic acid (IC<sub>50</sub> 83 vs 93 μM). In summary, the novel compounds, 1a-k, proved to chelate various borderline/soft Lewis acid metal-ions, and may be useful as antioxidants and metal extractors.
Elkin T., Kulkarni N. V., Tumanskii B., Botoshansky M., Shimon L. J. & Eisen M. S. (2013) Organometallics. 32, 21, p. 6337-6352
The steric properties of various nitrogen substituents on amidines were tuned in order to obtain group 4 mono- and bis(amidinate) dimethylamido or chloride complexes. The amidinate dimethylamido and chloride complexes were prepared, and their solid-state as well as their solution-state structures were studied. After the activation by MAO, these complexes were tested in the polymerization of propylene and ethylene. A noticeable influence of the amidine carbon and nitrogen substituents on the activity of the catalyst and properties of the obtained polymer was observed. Further, a plausible mechanism for the ethylene polymerization process is presented taking into account a combination of ESR-C<sub>60</sub> and MALDI-TOF experiments, shedding light on the nature of the catalytic species.
Srimani D., Diskin Posner Y., Ben-David Y. & Milstein D. (2013) Angewandte Chemie - International Edition. 52, 52, p. 14131-14134
Ironing out hydrogenation: For the first time, an iron catalyst provided chemo- and stereo-selective semi-hydrogenation of alkynes to E-alkenes. This efficient, atom-economical reaction is catalyzed by a novel acridine-based PNP iron pincer catalyst and exhibits excellent functional group tolerance under mild, neutral, environmentally benign reaction conditions.
Gidron O., Diskin Posner P. Y. & Bendikov M. (2013) Chemistry-A European Journal. 19, 39, p. 13140-13150
The extent of charge delocalization and of conjugation in oligofurans and oligothiophenes was studied by using mixed valence systems comprising oligofurans and oligothiophenes capped at both ends by ferrocenyl redox units. Using electrochemical, spectral, and computational tools, we find strong charge delocalization in ferrocene-capped oligofurans which was stronger than in the corresponding oligothiophene systems. Spectroscopic studies suggest that the electronic coupling integral (H<sub>ab</sub>) is roughly 30-50 % greater for oligofuran-bridged systems, indicating better energy matching between ferrocene units and oligofurans. The distance decay constant (damping factor), β, is similar for oligofurans (0.066A<sup>-1</sup>) and oligothiophenes (0.070A <sup>-1</sup>), which suggests a similar extent of delocalization in the bridge, despite the higher HOMO-LUMO gap in oligofurans. Computational studies indicate a slightly larger extent of delocalization in furan-bridged systems compared with thiophene-bridged systems, which is consistent with oligofurans being significantly more rigid and less aromatic than oligothiophenes. High charge delocalization in oligofurans, combined with the previously reported strong fluorescence, high mobility, and high rigidity of oligofuran-based materials makes them attractive candidates for organic electronic applications. The extent of charge delocalization and conjugation in oligofurans was studied by using mixed valence systems comprising oligofurans capped at both ends by ferrocenyl redox units, and compared with the corresponding oligothiophenes. Oligofurans show excellent charge delocalization and conjugation similar to oligothiophenes (see figure), which makes them promising candidates for applications such as organic semiconductors and molecular wires.
Khaskin E., Diskin Posner Y., Weiner L., Leitus G. & Milstein D. (2013) Chemical Communications. 49, 27, p. 2771-2773
A (PNP)Co(i)methyl diamagnetic complex formally loses an H atom from the pincer ligand, exhibiting a long-range metalligand cooperation in what may be considered as an unusual example of \u201cCH cleavage\u201d. Spectroscopic data indicate that the product is a neutral Co(i) complex with a radical delocalized in the ligand backbone.
Orbach M., Zenkina O. V., Diskin Posner Y., Iron M. A. & van der Boom M. E. (2013) Organometallics. 32, 10, p. 3074-3082
We present a mechanistic study demonstrating selective Ar<sub>f</sub>-Cl bond activation preceded by η<sup>2</sup> coordination of Pd(PEt <sub>3</sub>)<sub>2</sub> to a C=C moiety of a partially fluorinated substrate. An intramolecular ring-walking process to activate the Ar<sub>f</sub>-Cl bond is plausible, but an intermolecular reaction becomes dominant in the presence of PEt<sub>3</sub>. The latter pathway is significantly enhanced, since PEt <sub>3</sub> promotes dissociation of Pd(PEt<sub>3</sub>)<sub>3</sub> from the C=C moiety followed by activation of the Ar<sub>f</sub>-Cl bond. Our observations also show that PEt<sub>3</sub> can be used to control reaction selectivity. The experimental observations are supported by density functional theory (DFT) calculations (at the SMD(toluene)-DSD-PBEP86/cc-pV(D+d)Z-PP//DF- PBE+d<sub>v2</sub>/SDD(d) level of theory).
Eldar A., Rozenberg H., Diskin Posner Y., Rohs R. & Shakked Z. (2013) Nucleic Acids Research. 41, 18, p. 8748-8759
A p53 hot-spot mutation found frequently in human cancer is the replacement of R273 by histidine or cysteine residues resulting in p53 loss of function as a tumor suppressor. These mutants can be reactivated by the incorporation of second-site suppressor mutations. Here, we present high-resolution crystal structures of the p53 core domains of the cancer-related proteins, the rescued proteins and their complexes with DNA. The structures show that inactivation of p53 results from the incapacity of the mutated residues to form stabilizing interactions with the DNA backbone, and that reactivation is achieved through alternative interactions formed by the suppressor mutations. Detailed structural and computational analysis demonstrates that the rescued p53 complexes are not fully restored in terms of DNA structure and its interface with p53. Contrary to our previously studied wild-type (wt) p53-DNA complexes showing non-canonical Hoogsteen A/T base pairs of the DNA helix that lead to local minor-groove narrowing and enhanced electrostatic interactions with p53, the current structures display Watson-Crick base pairs associated with direct or water-mediated hydrogen bonds with p53 at the minor groove. These findings highlight the pivotal role played by R273 residues in supporting the unique geometry of the DNA target and its sequence-specific complex with p53.
Yaniv O., Halfon Y., Shimon L. J., Bayer E. A., Lamed R. & Frolow F. (2012) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 68, 1, p. 8-13
The carbohydrate-binding module (CBM) of the major scaffoldin subunit ScaA of the cellulosome of Acetivibrio cellulolyticus is classified as a family 3b CBM and binds strongly to cellulose. The CBM3b was overexpressed, purified and crystallized, and its three-dimensional structure was determined. The structure contained a nickel-binding site located at the N-terminal region in addition to a classical CBM3b calcium-binding site. The structure was also determined independently by the SAD method using data collected at the Ni-absorption wavelength of 1.48395 Å and even at a wavelength of 0.97625 Å in a favourable case. The new scaffoldin-borne CBM3 structure reported here provides clear evidence for the proposition that a family 3b CBM may be accommodated in scaffoldin subunits and functions as the major substrate-binding entity of the cellulosome assembly.
Yaniv O., Petkun S., Shimon L. J., Bayer E. A., Lamed R. & Frolow F. (2012) Acta Crystallographica Section D: Biological Crystallography. 68, 7, p. 819-828
The crystal structure of the family 3b carbohydrate-binding module (CBM3b) of the cellulosomal multimodular hydrolytic enzyme cellobiohydrolase 9A (Cbh9A) from Clostridium thermocellum has been determined. Cbh9A CBM3b crystallized in space group P41 with four molecules in the asymmetric unit and diffracted to a resolution of 2.20 Å using synchrotron radiation. The structure was determined by molecular replacement using C. thermocellum Cel9V CBM3b (PDB entry 2wnx) as a model. The C. thermocellum Cbh9A CBM3b molecule forms a nine-stranded antiparallel β-sandwich similar to other family 3 carbo-hydrate-binding modules (CBMs). It has a short planar array of two aromatic residues that are assumed to bind cellulose, yet it lacks the ability to bind cellulose. The molecule contains a shallow groove of unknown function that characterizes other family 3 CBMs with high sequence homology. In addition, it contains a calcium-binding site formed by a group of amino-acid residues that are highly conserved in similar structures. After determination of the three-dimensional structure of Cbh9A CBM3b, the site-specific N126W mutant was produced with the intention of enhancing the cellulose-binding ability of the CBM. Cbh9A CBM3b<sup>N126W</sup> crystallized in space group P41212, with one molecule in the asymmetric unit. The crystals diffracted to 1.04 Å resolution using synchrotron radiation. The structure of Cbh9A CBM3b <sup>N126W</sup> revealed incorporation of the mutated Trp126 into the putative cellulose-binding strip of residues. Cellulose-binding experiments demonstrated the ability of Cbh9A CBM3b<sup>N126W</sup> to bind cellulose owing to the mutation. This is the first report of the engineered conversion of a non-cellulose-binding CBM3 to a binding CBM3 by site-directed mutagenesis. The three-dimensional structure of Cbh9A CBM3b<sup>N126W</sup> provided a structural correlation with cellulose-binding ability, revealing a longer planar array of definitive cellulose-binding residues.
Gidron O., Shimon L. J., Leitus G. & Bendikov M. (2012) Organic Letters. 14, 2, p. 502-505
Taking advantage of the synthetic availability and solubility of long oligofurans, their reactivity toward dienophiles was studied as a model for the rarely investigated reactivity of long conjugated systems. Unlike oligoacenes, the reactivity of oligofurans decreases or remains constant with increasing chain length. Terminal ring cycloadducts of oligofurans are kinetically and thermodynamically favored, whereas central ring cycloadducts are preferred in oligoacenes, because of the different driving forces in the two reactions: π-conjugation in oligofurans and aromatization/dearomatization in oligoacenes.
Salama-Alber O., Gat Y., Lamed R., Shimon L. J., Bayer E. A. & Frolow F. (2012) Acta Crystallographica Section F:Structural Biology Communications. 68, 9, p. 1116-1119
In Ruminococcus flavefaciens, a predominant fibre-degrading bacterium found in ruminants, cellulosomal proteins are anchored to the bacterial cell wall through a relatively small ScaE scaffoldin which includes a single type III cohesin. The cotton-binding protein CttA consists of two cellulose-binding modules and a C-terminal modular pair (XDoc) comprising an X-module and a contiguous dockerin, which exhibits high affinity towards the ScaE cohesin. Seleno-l-methionine-labelled derivatives of the ScaE cohesin module and the XDoc from CttA have been expressed, copurified and cocrystallized. The crystals belonged to the tetragonal space group P4<sub>3</sub>2<sub>1</sub>2, with unit-cell parameters a = b = 78.7, c = 203.4 Å, and the unit cell contains a single cohesin-XDoc complex in the asymmetric unit. The diffraction data were phased to 2.0 Å resolution using the anomalous signal of the Se atoms.
Gargir M., Ben-David Y., Leitus G., Diskin Posner Y., Shimon L. J. W. & Milstein D. (2012) Organometallics. 31, 17, p. 6207-6214
The PNS pincer-type ligand 1 and the novel Ru(PNS) complexes 2-8 were synthesized and characterized. The (PNS)RuH(Cl)CO complex 2 was prepared by reaction of ligand 1 with RuH(Cl)CO(PPh <sub>3</sub>) <sub>3</sub>. 2 reacted with KHMDS (potassium bis(trimethylsilyl)amide) to form the symmetrical dimeric complex 4 via the intermediacy of the dearomatized complex (PNS*)Ru(H)CO 3, in which deprotonation of the benzylic-S "arm" took place. Reaction of 2 with excess NaH gave the dimeric 4, by a formal intermolecular attack of the benzylic "arm" on a second ruthenium center. Complex 4 underwent spontaneous transformation in solution to the dinuclear complex 5 via C-S bond cleavage, resulting in the loss of a S-bound <sup>t</sup>Bu group. Treatment of 2 with KHMDS in the presence of PEt <sub>3</sub> resulted in the trapping of intermediate 3 in the form of the dearomatized complex 8. Reaction of 2 with LiHBEt <sub>3</sub> gave the trans-dihydride complex 6, which reacted with CO <sub>2</sub> to give the formato complex 7, in which the formato ligand is located trans to the hydride. Complexes 2, 4, and 5 were also investigated as catalysts for the dehydrogenative coupling of alcohols with amines.
Feller M., Diskin Posner Y., Shimon L. J. W., Ben-Ari E. & Milstein D. (2012) Organometallics. 31, 11, p. 4083-4101
In continuation of our studies on bond activation and catalysis by pincer complexes, based on metal-ligand cooperation, we present here a rare example of amine N-H activation by Rh(I) complexes. The novel dearomatized pincer complexes [(PNN*)RhL] (PNN = 2-(CH <sub>2</sub>-P <sup>t</sup>Bu <sub>2</sub>)-6-(CH <sub>2</sub>-NEt <sub>2</sub>)C <sub>5</sub>H <sub>3</sub>N, PNN* = deprotonated PNN, L = N <sub>2</sub> (5), C <sub>2</sub>H <sub>4</sub> (6)) and [( <sup>i</sup>PrPNP)RhL] ( <sup>i</sup>PrPNP = 2,6-(CH <sub>2</sub>-P <sup>i</sup>Pr <sub>2</sub>) <sub>2</sub>C <sub>5</sub>H <sub>3</sub>N, <sup>i</sup>PrPNP* = deprotonated <sup>i</sup>PrPNP, L = C <sub>2</sub>H <sub>4</sub> (7), cyclooctene (9)) were prepared and fully characterized by NMR and X-ray analysis. Complexes 5-7 and 9 undergo facile N-H activation of anilines involving aromatization of the pincer ligand without a change in the formal oxidation state of the metal center to form stable anilide complexes [(PNN)Rh(NHAr)] and [( <sup>i</sup>PrPNP)Rh(NHAr)] (Ar = C <sub>6</sub>H <sub>5</sub>, o-Br-C <sub>6</sub>H <sub>4</sub>, m-Cl-p-Cl-C <sub>6</sub>H <sub>3</sub>, p-NO <sub>2</sub>-C <sub>6</sub>H <sub>4</sub>). Anilines possessing electron-withdrawing groups accelerate the N-H activation and yield more stable anilide complexes. The pincer and the ancillary ligands also affect the activation rate, which supports an associative mechanism. Spin saturation transfer experiments show chemical exchange between the pyridylic arm of the pincer ligand and the NH- protons of anilines prior to and after the N-H activation. The reverse N-H formation by metal-ligand cooperation from the anilide complexes was observed to give free anilines and dearomatized Rh(I) complexes upon addition of CO or PEt <sub>3</sub>. Deprotonation of complexes [(PNL)Rh(p-NO <sub>2</sub>-NH <sub>2</sub>C <sub>6</sub>H <sub>4</sub>)] (13, P = P <sup>t</sup>Bu <sub>2</sub>, L = NEt <sub>2</sub>; 15, P = L = P <sup>i</sup>Pr <sub>2</sub>) yields the dearomatized anionic complexes [(PNL)Rh(p-NO <sub>2</sub>-NH <sub>2</sub>C <sub>6</sub>H <sub>4</sub>)]. An associative mechanism, involving N-H activation of an apically coordinated aniline in a pentacoordinated Rh(I) complex, is suggested.
Vogt M., Gargir M., Iron M. A., Diskin Posner Y., Ben-David Y. & Milstein D. (2012) Chemistry - A European Journal. 18, 30, p. 9194-9197
Team work: Although CO2 binding to metal centers usually involves π coordination to a C-O group or σ bonds to the carbon or oxygen atom of the CO2 molecule, a new mode of metalligand cooperative activation of CO2 to a ruthenium PNP pincer complex involving aromatization/dearomatization steps is presented in experimental and theoretical studies (see scheme).
Orbach M., Choudhury J., Lahav M., Zenkina O. V., Diskin Posner Y., Leitus G., Iron M. A. & van der Boom M. E. (2012) Organometallics. 31, 4, p. 1271-1274
We report here that the undesired hydrodehalogenation in cross-coupling reactions with fluorinated substrates involves water as a possible hydrogen source. Moreover, the product distribution (hydrodehalogenation vs carbon-carbon coupling) can be controlled by varying the phosphine substituents. Significant hydrodehalogenation occurs prior to the formation of Ar <sub>F</sub>-Pd(II)-Br complexes. DFT calculations were used to evaluate a direct hydrodehalogenation route with a phosphine and water. These findings provide new mechanistic insight into aryl-Br bond activation with fluorinated substrates and selective arene functionalization.
Montag M., Efremenko I., Diskin Posner Y., Ben-David Y., Martin J. M. L. & Milstein D. (2012) Organometallics. 31, 1, p. 505-512
The room-temperature reaction between the Rh(I) precursor [Rh(COE) <sub>2</sub>(acetone) <sub>2</sub>]BF <sub>4</sub> (COE = cyclooctene) and a new thiophosphoryl-based SCS pincer ligand leads to oxidative addition of an sp <sup>2</sup>-sp <sup>3</sup> C-C bond as the only observed outcome, despite the presence of accessible sp <sup>3</sup> C-H bonds. A DFT study reveals that the chemistry of the SCS system is controlled by π repulsion between occupied rhodium d orbitals and the lone-pair electrons on the two sulfur atoms. This repulsion gives rise to the thermodynamic selectivity for C-C over C-H cleavage, as it is attributed to the higher electronegativity of a methyl versus hydride ligand, thereby allowing more effective release of excessive π electron density. It is also demonstrated that the observed C-C and unobserved C-H cleavage pathways originate from a common intermediate that features a novel ν <sup>3</sup>-C-C-H agostic interaction. The COE ligand is shown to play an important role by greatly stabilizing this intermediate, making it the only available entry point to both reaction pathways.
Langer R., Iron M. A., Konstantinovski L., Diskin Posner Y., Leitus G., Ben-David Y. & Milstein D. (2012) Chemistry - A European Journal. 18, 23, p. 7196-7209
The new, structurally characterized hydrido carbonyl tetrahydridoborate iron pincer complex [(iPr-PNP)Fe(H)(CO)(η<sup>1</sup>-BH <sub>4</sub>)] (1) catalyzes the base-free hydrogenation of ketones to their corresponding alcohols employing only 4.1atm hydrogen pressure. Turnover numbers up to 1980 at complete conversion of ketone were reached with this system. Treatment of 1 with aniline (as a BH<sub>3</sub> scavenger) resulted in a mixture of trans-[(iPr-PNP)Fe(H)<sub>2</sub>(CO)] (4a) and cis-[(iPr-PNP)Fe(H) <sub>2</sub>(CO)] (4b). The dihydrido complexes 4a and 4b do not react with acetophenone or benzaldehyde, indicating that these complexes are not intermediates in the catalytic reduction of ketones. NMR studies indicate that the tetrahydridoborate ligand in 1 dissociates prior to ketone reduction. DFT calculations show that the mechanism of the iron-catalyzed hydrogenation of ketones involves alcohol-assisted aromatization of the dearomatized complex [(iPr-PNP*)Fe(H)(CO)] (7) to initially give the Fe<sup>0</sup> complex [(iPr-PNP)Fe(CO)] (21) and subsequently [(iPr-PNP)Fe(CO)(EtOH)] (38). Concerted coordination of acetophenone and dual hydrogen-atom transfer from the PNP arm and the coordinated ethanol to, respectively, the carbonyl carbon and oxygen atoms, leads to the dearomatized complex [(iPr-PNP*)Fe(CO)(EtO)(MeCH(OH) Ph)] (32). The catalyst is regenerated by release of 1-phenylethanol, followed by dihydrogen coordination and proton transfer to the coordinated ethoxide ligand.
Kossoy E., Diskin Posner Y., Leitus G. & Milstein D. (2012) Advanced Synthesis & Catalysis. 354, 2-3, p. 497-504
The complex bis(acetonitrile)bis(triphenylphosphine)ruthenium(II) sulfate [Ru(PPh <sub>3</sub>) <sub>2</sub>(NCCH <sub>3</sub>) <sub>2</sub>(SO <sub>4</sub>)], fully characterized spectroscopically and by a single crystal X-ray study, catalyzes at 110 °C the direct transformation of primary alcohols to the corresponding acetals with liberation of molecular hydrogen. The formation of acetals proceeds via direct substitution of the hydroxy group of the hemiacetal intermediate by an alcohol molecule. The closely related bis(triphenylphosphine) ruthenium(II) acetate [Ru(PPh <sub>3</sub>) <sub>2</sub>(OAc) <sub>2</sub>] catalyzes the conversion of primary alcohols to the corresponding esters rather than acetals.
Voronov-Goldman M., Lamed R., Noach I., Borovok I., Kwiat M., Rosenheck S., Shimon L. J., Bayer E. A. & Frolow F. (2011) Proteins-Structure Function And Bioinformatics. 79, 1, p. 50-60
The increasing numbers of published genomes has enabled extensive survey of protein sequences in nature. During the course of our studies on cellulolytic bacteria that produce multienzyme cellulosome complexes designed for efficient degradation of cellulosic substrates, we have investigated the intermodular cohesin-dockerin interaction, which provides the molecular basis for cellulosome assembly. An early search of the genome databases yielded the surprising existence of a dockerin-like sequence and two cohesin-like sequences in the hyperthermophilic noncellulolytic archaeon, Archaeoglobus fulgidus, which clearly contradicts the cellulosome paradigm. Here, we report a biochemical and biophysical analysis, which revealed particularly strong- and specific-binding interactions between these two cohesins and the single dockerin. The crystal structure of one of the recombinant cohesin modules was determined and found to resemble closely the type-I cohesin structure from the cellulosome of Clostridium thermocellum, with certain distinctive features: two of the loops in the archaeal cohesin structure are shorter than those of the C. thermocellum structure, and a large insertion of 27-amino acid residues, unique to the archaeal cohesin, appears to be largely disordered. Interestingly, the cohesin module undergoes reversible dimer and tetramer formation in solution, a property, which has not been observed previously for other cohesins. This is the first description of cohesin and dockerin interactions in a noncellulolytic archaeon and the first structure of an archaeal cohesin. This finding supports the notion that interactions based on the cohesin-dockerin paradigm are of more general occurrence and are not unique to the cellulosome system. Proteins 2010.
Yaniv O., Shimon L. J., Bayer E. A., Lamed R. & Frolow F. (2011) Acta Crystallographica Section D: Biological Crystallography. 67, 6, p. 506-515
The potent cellulose-binding modules of cellulosomal scaffoldin subunits belong to the greater family of carbohydrate-binding modules (CBMs). They have generally been classified as belonging to family 3a on the basis of sequence similarity. They form nine-stranded Β-sandwich structures with jelly-roll topology. The members of this family possess on their surface a planar array of aromatic amino-acid residues (known as the linear strip) that form stacking interactions with the glucose rings of cellulose chains and have a conserved Ca<sup>2+</sup>-binding site. Intriguingly, the CBM3 from scaffoldin A (ScaA) of Bacteroides cellulosolvens exhibits alterations in sequence that make it more similar to the CBMs of free cellulolytic enzymes, which are classified into CBM family 3b. X-ray structural analysis was undertaken in order to examine the structural consequences of the sequence changes and the consequent family affiliation. The CBM3 crystallized in space group I4122 with one molecule in the asymmetric unit, yielding diffraction to a resolution of 1.83 Å using X-ray synchrotron radiation. Compared with the known structures of other scaffoldin-borne CBMs, a sequence insertion and deletion appear to compensate for each other as both contained an aromatic residue that is capable of contributing to cellulose binding; hence, even though there are alterations in the composition and localization of the aromatic residues in the linear strip its binding ability was not compromised. Interestingly, no Ca<sup>2+</sup> ions were detected in the conserved calcium-binding site, although the module was properly folded; this suggests that the structural role of Ca<sup>2+</sup> is less important than originally supposed. These observations indicate that despite their conserved function the scaffoldin-borne CBMs are more diverse in their sequences and structures than previously assumed.
Livanov K., Madhu V., Balaraman E., Shimon L. J. W., Diskin Posner Y. & Neumann R. (2011) Inorganic Chemistry. 50, 22, p. 11273-11275
The catalytic photocleavage of CS<sub>2</sub> to S<sub>8</sub> and a (C<sub>x</sub>S<sub>y</sub>)<sub>n</sub> polymer with visible light using a dinuclear ruthenium(II) compound with a bipyridine units for photoactivity and a vicinal tertiary amine binding site for CS<sub>2</sub> activation was studied. The catalyst was characterized by X-ray diffraction, <sup>1</sup>H NMR, and <sup>13</sup>C NMR, ESI-MS and elemental analysis. CS<sub>2</sub> photocleavage was significant (240 turnovers, 20 h) to yield isolable S<sub>8</sub> and a (C<sub>x</sub>S<sub>y</sub>)<sub>n</sub> polymer. A mononuclear catalyst or one without an amine binding site showed significantly less activity. XPS of the (C<sub>x</sub>S<sub>y</sub>)<sub>n</sub> polymer showed a carbon/sulfur ratio ∼1.5-1.6 indicating that in part both C-S bonds of CS<sub>2</sub> had been cleaved. Catalyst was also included within the polymer. The absence of peaks in the <sup>1</sup>H NMR verified the (C<sub>x</sub>S<sub>y</sub>)<sub>n</sub> nature of the polymer, while <sup>13</sup>C NMR and IR indicated that the polymer had multiple types of C-S and C-C bonds.
Salem H., Leitus G., Shimon L. J. W., Diskin Posner Y. & Milstein D. (2011) Inorganica Chimica Acta. 369, 1, p. 260-269
Treatment of 7,8-benzo[h]quinoline (bhq-H, 1) and 10-methyl benzo[h]quinoline (bhq-Me, 3) with [Rh(C<sub>2</sub>H<sub>4</sub>) <sub>2</sub>(THF)<sub>2</sub>][BF<sub>4</sub>] resulted in double C-H activation of aliphatic and aromatic C-H bonds, yielding the Rh(III) complexes 4 and 5, respectively. The structures of 4 and 5 were revealed by X-ray diffraction. The reaction of 1 with two other slightly different rhodium precursors, [Rh(olefin)<sub>n</sub>(THF)<sub>2</sub>][BF<sub>4</sub>] (COE (n = 2), COD (n = 1)), led to completely different products, a dinuclear complex 7 and a trinuclear complex 6, respectively, which were characterized by X-ray diffraction. Complex 6 exhibits a rare linear Rh-Rh-Rh structure. Utilizing excess of 1 with [Rh(COD)(THF)<sub>2</sub>][BF<sub>4</sub>] led to the formation of a new product 8 with no C-H bond activation taking place. Additional C-H activation products of 1, cationic and neutral, in the presence of P <sup>i</sup>Pr<sub>3</sub> (9a, 9b and 10) are also presented.
Langer R., Diskin Posner Y., Leitus G., Shimon L. J. W., Ben-David Y. & Milstein D. (2011) Angewandte Chemie - International Edition. 50, 42, p. 9948-9952
A highly active iron catalyst for the hydrogenation of carbon dioxide and bicarbonates works under remarkably low pressures and achieves activities similar to some of the best noble metal catalysts. A mechanism is proposed involving the direct attack of an iron transdihydride on carbon dioxide, followed by ligand exchange and dihydrogen coordination.
Fogler E., Balaraman E., Ben-David Y., Leitus G., Shimon L. J. W. & Milstein D. (2011) Organometallics. 30, 14, p. 3826-3833
Figure Presented: New pincer ruthenium complexes (2-6) based on the new bipyridine-NHC ligand 1 were prepared and studied, resulting in an efficient catalytic hydrogenation of esters to the corresponding alcohols under mild conditions. Reaction of the ligand 1 with RuH(Cl)CO(PPh<sub>3</sub>) <sub>3</sub>, followed by reaction with one equivalent of the base KHMDS, gave the mixed phosphine-NHC complex 2, incorporating a C-H-activated bipyridine ligand. Complex 2 has an octahedral structure containing two phosphorus atoms trans to each other, a hydride trans to the NHC ligand, and CO trans to the C-H-activated carbon of the bipyridine ligand. Using the precursor complex Ru(p-cymene)Cl<sub>2</sub>(CO), reaction with 1 followed by treatment of the intermediate product with one equivalent of KHMDS resulted in formation of the dichloride pincer complexes 3a and 3b, which are in equilibrium, as indicated by variable-temperature <sup>1</sup>H NMR. Complex 3a is an octahedral, neutral, and symmetric complex with the CO ligand positioned trans to the central pyridine group of the pincer ligand and the two chlorides trans to each other, as indicated by single-crystal X-ray diffraction. Complex 3b is cationic, with an outer-sphere chloride. Reaction of the NHC ligand 1 with LiHMDS at low temperature followed by addition of RuH(Cl)CO(PPh<sub>3</sub>)<sub>3</sub> resulted in the mixed phosphine-NHC complex 4, which has an octahedral structure containing phosphorus trans to the hydride, a CO trans to the NHC ligand, and an outer-sphere chloride. Chloride substitution by BAr<sup>F-</sup> gave the X-ray-characterized complex 5. Deprotonation of complex 4 with KHMDS resulted in formation of the dearomatized complex 6. The in situ prepared 6 (from complex 4 and an equivalent of base) is among the best catalysts known for the hydrogenation of nonactivated esters to the corresponding alcohols under mild conditions.
Balaraman E., Gunanathan C., Zhang J., Shimon L. J. W. & Milstein D. (2011) Nature Chemistry. 3, 8, p. 609-614
Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO <sub>2</sub> and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO <sub>2</sub> and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate 'green' reactions. A possible mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core.
Madhu V., Diskin Posner Y. & Neumann R. (2011) European Journal of Inorganic Chemistry. 11, p. 1792-1796
Copper(I) complexes with perfluorinated tails, (Cu<sup>I</sup>L <sup>2</sup>AcN)BF<sub>4</sub> and (Cu<sup>I</sup>L<sup>3</sup>AcN)BF <sub>4</sub>, where L<sup>2</sup> = 6,6-bis(perfluorohexyl)-2,2: 6,2-terpyridine and L<sup>3</sup> = 6,6-bis(2,2,3,3,4,4,5, 5,6,6,7,7,7-tridecafluoroheptyl)-2,2-bipyridine and AcN = acetonitrile, were synthesized and their rather unique crystal structures were elucidated. (Cu<sup>I</sup>L<sup>2</sup>AcN)BF<sub>4</sub> crystallizes in a low-symmetry space group, P$\bar {1}$, with a very large unit cell that required synchrotron radiation to locate all atoms. The molecular structure of (Cu<sup>I</sup>L<sup>2</sup>AcN)BF<sub>4</sub> has an asymmetric tetrahedrally distorted square-planar coordination sphere around Cu<sup>I</sup>. Eight similar but distinct molecular structures were found. The crystal packing of (Cu <sup>I</sup>L<sup>2</sup>AcN)(BF<sub>4</sub>) has a layered structure with a clear segregation between the terpyridine moieties and the fluorous chains. The terpyridine units are arranged in a "back to back" fashion and tilted 20-25° relative to the interlayer plane, and the layered structure is staggered with offsets of approximately 4 Å between layers. The molecular structure of (Cu<sup>I</sup>L<sup>3</sup>AcN)(BF<sub>4</sub>) features a Y-shaped trigonal planar coordination sphere around copper(I). Comparison of the structure with analogous Cu<sup>I</sup>(neocuproine)AcN showed that the fluorous tails with the CH<sub>2</sub>CH<sub>2</sub> spacers basically have no effect on the bond lengths and angles to Cu<sup>1</sup>. The crystal structure of (Cu<sup>I</sup>L<sup>3</sup>AcN)(BF<sub>4</sub>) shows a "herring bone" conformation with an approximately 96° angle in the CubipyAcN units. The "herring bone" conformation leads to an accordion-type fluorous layer. Copper(I) complexes of bipyridine (Y-shaped trigonal planar) and terpyridine (tetrahedrally distorted square-planar) with fluorous tails showed crystal packing with segregation of the aromatic units and the fluorous tails. Layered structures that are tilted in two different dimensions as well as "herring bone" structures with accordion-like fluorous layers were observed.
Ettedgui J., Diskin Posner Y., Weiner L. & Neumann R. (2011) Journal of the American Chemical Society. 133, 2, p. 188-190
A phenanthroline ligand decorated at the 5,6-position with a 15-crown-5 ether was used to prepare a metalorganic-polyoxometalate hybrid complex Re <sup>I</sup>(L)(CO)<sub>3</sub>CH<sub>3</sub>CN-MHPW<sub>12</sub>O<sub>40</sub> (L = 15-crown-5-phenanthroline, M = Na<sup>+</sup>, H<sub>3</sub>O<sup>+</sup>). X-ray diffraction, <sup>1</sup>H and <sup>13</sup>C NMR, ESI-MS, IR, and elemental analysis were used to characterize this complex. In the presence of Pt/C, the polyoxometalate moiety in Re<sup>I</sup>(L)(CO)<sub>3</sub>CH <sub>3</sub>CN-MHPW<sub>12</sub>O<sub>40</sub> can oxidize H<sub>2</sub> to two protons and two electrons which in the presence of visible light can catalyze the photoreduction of CO<sub>2</sub> to CO with H<sub>2</sub> as the reducing agent instead of the universally used amines as sacrificial reducing agents. An EPR spectrum of a stable intermediate species under reaction conditions shows characteristics of a PW<sup>V</sup>W<sup>VI</sup><sub>11</sub>O<sub>40</sub> and a Re<sup>0</sup> species with a tentative assignment of the intermediate as Re<sup>0</sup>(L)(CO)<sub>3</sub>(S)-MH<sub>3</sub>PW<sup>V</sup>W <sup>VI</sup><sub>11</sub>O<sub>40</sub>.
Gunanathan C., Gnanaprakasam B., Iron M. A., Shimon L. J. W. & Milstein D. (2010) Journal of the American Chemical Society. 132, 42, p. 14763-14765
The acridine-based pincer complex 1 exhibits an unprecedented mode of metal-ligand cooperation involving a "long-range" interaction between the distal acridine C9 position and the metal center. Reaction of 1 with H <sub>2</sub>/KOH results in H<sub>2</sub> splitting between the Ru center and C9 with concomitant dearomatization of the acridine moiety. DFT calculations show that this process involves the formation of a Ru dihydride intermediate bearing a bent acridine ligand in which C9 is in close proximity to a hydride ligand followed by through-space hydride transfer. Ammonia induces transfer of a hydride from the Ru center of 1 to C9 of the flexible acridine pincer ligand, forming an unusual dearomatized fac-acridine PNP complex.
Montag M., Efremenko I., Cohen R., Shimon L. J. W., Leitus G., Diskin Posner Y., Ben-David Y., Salem H., Martin J. M. L. & Milstein D. (2010) Chemistry - A European Journal. 16, 1, p. 328-353
Sequential addition of CO molecules to cationic aryl-hydrido Rh <sup>III</sup> complexes of phosphine-based (PCP) pincer ligands was found to lead first to C-H reductive elimination and then to C-H oxidative addition, thereby demonstrating a dual role of CO. DFT calculations indicate that the oxidative addition reaction is directly promoted by CO, in contrast to the commonly accepted view that CO hinders such reactions. This intriguing effect was traced to repulsive JT interactions along the aryl-Rh-CO axis, which are augmented by the initially added CO ligand (due to antibonding interactions between occupied Rh d<sub>π</sub> orbitals and occupied π orbitals of both CO and the arene moiety), but counteracted by the second CO ligand (due to significant π back-donation). These repulsive interactions were themselves linked to significant weakening of the π-acceptor character of CO in the positively charged rhodium complexes, which is concurrent with an enhanced o-donating capability. Replacement of the phosphine ligands by an analogous phosphinite-based (POCOP) pincer ligand led to significant changes in reactivity, whereby addition of CO did not result in C-H reductive elimina-tion, but yielded relatively stable mono- and dicarbonyl aryl-hydrido POCOP-Rh <sup>III</sup> complexes. DFT calculations showed that the stability of these complexes arises from the higher electrophilicity of the POCOP ligand, relative to PCP, which leads to partial reduction of the excessive π-electron density along the aryl-Rh-CO axis. Finally, comparison between the effects of CO and acetonitrile on C-H oxidative addition revealed that they exhibit similar reactivity, despite their markedly different electronic properties. However, DFT calculations indicate that the two ligands operate by different mechanisms.
Schwartsburd L., Iron M. A., Konstantinovski L., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2010) Organometallics. 29, 17, p. 3817-3827
The complex (PNP)Ir<sup>I</sup>(CH<sub>2</sub>COCH<sub>3</sub>) 2 (PNP = 2,6-bis((di-tert-butylphosphino)methyl)pyridine) was prepared by reaction of the dearomatized, electron-rich complex (PNP)Ir<sup>I</sup>(COE) (1; PNP* = deprotonated PNP, COE = cyclooctene) with acetone. Upon treatment with CO, complex 2 undergoes a surprising elimination of acetone to form the dearomatized species (PNP)Ir<sup>I</sup>(CO) (4), involving proton migration from the ligand "arm" to the acetonyl moiety. DFT studies reveal that this process occurs via the square-pyramidal intermediate 2+CO, formed upon CO coordination to 2, in which the acetonyl moiety is located at the apical position prior to proton migration. Reaction of 2 with H<sub>2</sub> (D<sub>2</sub>) indicates an equilibrium between complex 2 and the nonaromatic (PNP)Ir<sup>III</sup>(H) (CH<sub>2</sub>COCH<sub>3</sub>) complex 2b, which is the species that actually activates H<sub>2</sub> to exclusively form the trans-dihydride (PNP)Ir <sup>III</sup>(H)<sub>2</sub>(CH<sub>2</sub>COCH<sub>3</sub>) (5a) and activates D<sub>2</sub> to form the trans-hydride-deuteride 5b with benzylic-D incorporation, as also corroborated by DFT studies. Interestingly, benzene C-H activation by complex 2 results in formation of the complex (PNP)Ir <sup>I</sup>(C<sub>6</sub>H<sub>5</sub>) (6a) and elimination of acetone. DFT studies show that the benzene C-H bond is actually activated by the dearomatized "bare" (PNP)Ir<sup>I</sup> intermediate 2c, formed upon acetone elimination from 2.
Laskavy A., Shimon L. J., Konstantinovski L., Iron M. A. & Neumann R. (2010) Journal of the American Chemical Society. 132, 2, p. 517-523
A ruthenium(II) bipyridine complex with proximal phenylselenium tethers, [Ru](H<sub>2</sub>O)<sub>2</sub>, reacted intramolecularly with O<sub>2</sub> in a protic slightly acidic solvent, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), to yield an O-O bond cleaved product, [Ru](O)<sub>2</sub>, with formation of two Ru-O-Se moieties. This stable compound was isolated, and its structure was determined by X-ray diffraction. The identification of the compound in solution was confirmed by ESI-MS and the <sup>1</sup>H NMR with the associated Curie plot that showed that [Ru](O)<sub>2</sub> was paramagnetic. The magnetic susceptibility was 2.8 μB by Evan's method suggesting a ground state triplet or biradical. DFT calculations, however, predicted a ground state singlet and an oxidized Se atom. Further it was shown that [Ru](O)<sub>2</sub> is a potent oxygen transfer species of both O<sub>2</sub>-derived atoms to triphenylphosphine and a nucleophilic alkene such as 2,3-dimethyl-2-butene in both HFIP and acetonitrile. UV-vis spectroscopy combined with the measured stoichiometry of PPh<sub>3</sub>:O<sub>2</sub> = ̃2 in a catalytic oxidation of PPh<sub>3</sub> suggests a dioxygenase type activation of O <sub>2</sub> with structural identification of the O-O bond cleavage reaction step, formation of [Ru](O)<sub>2</sub> as an intermediate, and the proof that [Ru](O)<sub>2</sub> is a donor of both oxygen atoms.
Kaminker R., Motiei L., Gulino A., Fragala I., Shimon L. J. W., Evmenenko G., Dutta P., Iron M. A. & van der Boom M. E. (2010) Journal of the American Chemical Society. 132, 41, p. 14554-14561
Metal-organic networks (MONs) were created by a stepwise solution deposition approach from vinylpyridine-based building blocks and PdCl <sub>2</sub>. The combined experimental and computational study demonstrates the formation of saturated, structurally organized systems on solid supports. The rigid nature and geometry of the components are well-suited to form honeycomb and parallelogram structures, as predicted by a computational study. Detailed structural information of the new MONs was obtained by optical (UV/vis) spectroscopy, ellipsometry, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and synchrotron X-ray reflectivity (XRR). Notably, the XPS elemental composition indicates the formation of a palladium coordination-based network.
Khaskin E., Iron M. A., Shimon L. J. W., Zhang J. & Milstein D. (2010) Journal of the American Chemical Society. 132, 25, p. 8542-8543
A nonoxidative addition pathway for the activation of NH bonds of ammonia and amines by a Ru(II) complex is reported. The pincer complex 1 cleaves N-H bonds via metal-ligand cooperation involving aromatization of the pincer ligand without a change in the formal oxidation state of the metal. Electron-rich N-H bond substrates lead to reversible activation, while electron-poor substrates result in stable activation products. Isotopic labeling studies using ND <sub>3</sub> as well as density functional theory calculations were used to shed light on the N-H activation mechanism.
Madhu V., Ekambaram B., Shimon L. J., Diskin Y., Leitus G. & Neumann R. (2010) Dalton Transactions. 39, 31, p. 7266-7275
A ditopic 1,2-bis(2,2-bipyridyl-6-yl)ethyne ligand, L, has been synthesized for the first time by consecutive Suzuki and Sonogashira coupling reactions either in a one- or two-step synthesis. Coordination of L with some first-row transition metals, Fe, Mn and Co showed a very rich structural diversity that can be obtained with this ligand. Reaction of L with Mn <sup>II</sup>(OAc)<sub>2</sub> yielded a dimanganese(ii) complex, [Mn <sub>2</sub>L(μ-OAc)<sub>3</sub>]PF<sub>6</sub>, (1) where the two somewhat inequivalent trigonal-bipyramidal Mn atoms separated by 3.381 Å are bridged by L and three acetate moieties. A similar reaction of L with Mn <sup>III</sup>(OAc)<sub>3</sub> yielded a very different dimanganese complex [Mn<sub>2</sub>L(OH)(OAc)<sub>2</sub>(DMF)<sub>2</sub>]PF <sub>6</sub>·DMF (2) where L is a E-1,2-bis(2,2-bipyridyl- 6-yl)ethene fragment that was formed in situ. The L ligand bridges between the two Mn centers, despite its trans configuration, which leads to a very strained ethene bridging moiety. The Mn atoms are also bridged by two acetate ligands and a hydroxy group that bridges between the Mn atoms and the ethene fragment; DMF completes the octahedral coordination around each Mn atom which are separated by 3.351 Å. A comproportionation reaction of L with Mn<sup>II</sup>(OAc)<sub>2</sub> and n-Bu<sub>4</sub>NMnO<sub>4</sub> yielded a tetramanganese compound, [Mn<sub>4</sub>(μ<sub>3</sub>-O)<sub>2</sub>(OAc) <sub>4</sub>(H<sub>2</sub>O)<sub>2</sub>L<sub>2</sub>](PF<sub>6</sub>) <sub>2</sub>·2CH<sub>3</sub>CN (3). Compound 3 has a dimer of dimers structure of the tetranuclear Mn core that consists of binuclear [Mn <sub>2</sub>O(OAc)<sub>2</sub>L]<sup>+</sup> fragment and a PF<sub>6</sub> anion. BVS calculations indicate that 3 is a mixed-valent 2Mn<sup>II</sup> plus 2Mn<sup>III</sup> compound where two [Mn<sup>II</sup><sub>2</sub>O(OAc) <sub>2</sub>L]<sup>+</sup> fragments are held together by Mn<sup>III</sup>-O inter-fragment linkers which have a distorted octahedral geometry. The Mn atoms in the [Mn<sub>2</sub>O(OAc)<sub>2</sub>L]<sup>+</sup> fragments have a capped square-pyramid configuration where an aqua ligand is capped on one of the faces. Although the aqua ligand is well within a bonding distance to a carbon atom of the proximal ethyne bridge, there does not appear to be an oxygen-carbon bond formation, rather the ligand is constrained in this position, as deduced by the observation that the bond lengths and angles of the ligand are essentially the same as those for the free ligand, L. Reaction of L with perchlorate or triflate salts of Fe(ii), Mn(ii) and Co(ii) in dry acetonitrile yielded binuclear triple helicate structures (2:3 metal to L ratios) [Fe<sub>2</sub>L <sub>3</sub>](CF<sub>3</sub>SO<sub>3</sub>)<sub>4</sub>·CH<sub>3</sub>CN (4), [Mn<sub>2</sub>L<sub>3</sub>](ClO<sub>4</sub>)<sub>4</sub>·1. 7CH<sub>3</sub>CN·1.65EtOEt (5) and [Co<sub>2</sub>L<sub>3</sub>] (ClO<sub>4</sub>)<sub>4</sub>·2CH<sub>3</sub>CN·2EtOEt (6) where each M(ii) center with a slightly distorted octahedral geometry is bridged by three of the ditopic ligands. The M-M distances varied; 5.961 Å (Mn), 6.233 Å (Co) 6.331 Å (Fe). Reaction of L with Co(ClO <sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O in wet acetonitrile yielded a dicobalto(iii) compound, [Co<sub>2</sub>L<sub>3</sub>(O) <sub>2</sub>](ClO<sub>4</sub>)<sub>2</sub>·H<sub>2</sub>O (7), with two types of L fragments; one bridging between the two Co centers and two non-bridging ligands, each bonded to a Co atom via one bipyridyl group where the other is non-bonding. The octahedral coordination sphere around each Co atom is completed by the formation of a cobalt-carbon bond from the two carbon atoms of the ethene moiety of the bridging ligand and by a hydroxy moiety that is also bonded to the ethene group of the non-bridging ligand. Reaction of L with Co(ClO<sub>4</sub>)<sub>2</sub>·6H<sub>2</sub>O in dry acetonitrile in the presence of Et<sub>3</sub>N yielded the tetracobalto(ii) complex {[Co <sub>2</sub>L<sub>4</sub>(OH)<sub>4</sub>](ClO<sub>4</sub>)<sub>4</sub>} <sub>2</sub> (8) with a unique twisted square configuration of cobalt ions with Co-Co distances of 3.938 to 4.131 Å. In addition to the L bridging ligand the Co atoms are linked by hydroxy moieties. Some preliminary catalytic studies showed that the Mn compounds 1 and 2 were active (high yield within 3 min) for alkene epoxidation with peracetic acid and hydrogen peroxide dismutation (catalase activity).
Goihberg E., Peretz M., Tel-Or S., Dym O., Shimon L., Frolow F. & Burstein Y. (2010) Biochemistry. 49, 9, p. 1943-1953
The cofactor-binding domains (residues 153-295) of the alcohol dehydrogenases from the thermophile Thermoanaerobacter hrockii (TbADH), the mesophilic bacterium Clostridium heijerinckii (CbADH), and the protozoan parasite Entamoeba histolytica (EhADH1) have been exchanged. Three chimeras have been constructed. In the first chimera, the cofactor-binding domain of thermophilic TbADH was replaced with the cofactor-binding domain of its mesophilic counterpart CbADH [chimera X21<sub>(TCT)</sub>]. This domain exchange significantly destabilized the parent thermophilic enzyme (AJi/2 = -18 °C). The reverse exchange in CbADH [chimera X22<sub>(TCT)</sub>]. however, had little effect on the thermal stability of the parent mesophilic protein. Furthermore, substituting the cofactor-binding domain of TbADH with the homologous domain of EhADHl [chimera X23<sub>(TET)</sub>] substantially reduced the thermal stability of the thermophilic ADH (ΔT<sub>1/2</sub> = -51 °C) and impeded the oligomerization of the enzyme. All three chimeric proteins and one of their site-directed mutants were crystallized, and their three-dimensional (3D) structures were determined. Comparison of the 3D structures of the chimeras and the chimeric mutant with the structures of their parent ADHs showed no significant changes to their Cα chains, suggesting that the difference in the thermal stability of the three parent ADHs and their chimeric mutants could be due to a limited number of substitutions located at strategic positions, mainly at the oligomerization interfaces. Indeed, stabilization of the chimeras was achieved, to a significant extent, either by introduction of a proline residue at a strategic position in the major horse liver ADH-type dimerization interface (ΔT<sub>1/2</sub> = 35 °C) or by introduction of intersubunit electrostatic interactions (Δ T <sub>1/2</sub> = 6 °C).
Noach I., Levy-Assaraf M., Lamed R., Shimon L. J., Frolow F. & Bayer E. A. (2010) Journal of Molecular Biology. 399, 2, p. 294-305
The cellulosome complex is composed of a conglomerate of subunits, each of which comprises a set of interacting functional modules. Scaffoldin (Sca), a major cellulosomal subunit, is responsible for organizing the cellulolytic subunits into the complex. This is accomplished by the interaction of two complementary classes of modules-a cohesin (Coh) module on the Sca subunit and a dockerin module on each of the enzymatic subunits. Although individual Coh modules from different cellulosomal scaffoldins have been subjected to intensive structural investigation, the Sca subunit in its entirety has not, and there remains a paucity of information on the arrangement and interactions of Cohs within the Sca subunit. In the present work, we describe the crystal structure of a type II Coh dyad from the ScaB "adaptor" Sca of Acetivibrio cellulolyticus. The ScaB Cohs are oriented in an "antiparallel" manner relative to one another, with their dockerin-interacting surfaces (β-strands 8-3-6-5) facing the same direction-aligned on the same plane. A set of extensive hydrophobic and hydrogen-bond contacts between the Cohs and the short interconnecting linker segment between them stabilizes the modular orientation. This Coh dyad structure provides novel information about Coh-Coh association and arrangement in the Sca and further insight into intermodular linker interactions. Putative structural arrangements of a hexamodular complex, composed of the Coh dyad bound to two X-dockerin modules, were suggested.
Petkun S., Jindou S., Shimon L. J., Rosenheck S., Bayer E. A., Lamed R. & Frolow F. (2010) Acta Crystallographica Section D: Biological Crystallography. 66, 1, p. 33-43
Family 3 carbohydrate-binding modules (CBM3s) are associated with both cellulosomal scaffoldins and family 9 glycoside hydrolases (GH9s), which are multi-modular enzymes that act on cellulosic substrates. CBM3s bind cellulose. X - ray crystal structures of these modules have established an accepted cellulose-binding mechanism based on stacking interactions between the sugar rings of cellulose and a planar array of aromatic residues located on the CBM3 surface. These planar-strip residues are generally highly conserved, although some CBM3 sequences lack one or more of these residues. In particular, CBM3b' from Clostridium thermocellum Cel9V exhibits such sequence changes and fails to bind cellulosic substrates. A crystallographic investigation of CBM3b' has been initiated in order to understand the structural reason(s) for this inability. CBM3b' crystallized in space group C222<sub>1</sub> (diffraction was obtained to 2.0 Å resolution in-house) with three independent molecules in the asymmetric unit and in space group P4<sub>1</sub>2<sub>1</sub>2 (diffraction was obtained to 1.79 Å resolution in-house and to 1.30 Å resolution at a synchrotron) with one molecule in the asymmetric unit. The molecular structure of Cel9V CBM3b' revealed that in addition to the loss of several cellulose-binding residues in the planar strip, changes in the backbone create a surface 'hump' which could interfere with the formation of cellulose-protein surface interactions and thus prevent binding to crystalline cellulose.
Balaraman E., Gnanaprakasam B., Shimon L. J. W. & Milstein D. (2010) Journal of the American Chemical Society. 132, 47, p. 16756-16758
The selective, direct hydrogenation of amides to the corresponding alcohols and amines with cleavage of the C-N bond was discovered. The expected products of C-O cleavage are not formed (except as traces in the case of anilides). The reaction proceeds under mild pressure and neutral, homogeneous conditions using a dearomatized, bipyridyl-based PNN Ru(II) pincer complex as a catalyst. The postulated mechanism involves metal-ligand cooperation by aromatization- dearomatization of the heteroaromatic pincer core and does not involve hydrolytic cleavage of the amide. The simplicity, generality, and efficiency of this environmentally benign process make it attractive for the direct transformations of amides to alcohols and amines in good to excellent yields.
Feller M., Ben-Ari E., Iron M. A., Diskin Posner Y., Leitus G., Shimon L. J. W., Konstantinovski L. & Milstein D. (2010) Inorganic Chemistry. 49, 4, p. 1615-1625
A series of cationic, neutral, and anionic Pd<sup>II</sup> and Pt <sup>II</sup> PNP (PNP = 2, 6-bis-(di-tert-butylphosphinomethyl)pyridine) complexes were synthesized. The neutral, dearomatized complexes [(PNP*)MX] (PNP* = deprotonated PNP; M= Pd, Pt; X = Cl, Me) were prepared by deprotonation of the PNP methylene group of the corresponding cationic complexes [(PNP)MX][Cl] with 1 equiv of base (KN(SiMe<sub>3</sub>)<sub>2</sub> or <sup>t</sup>BuOK), while the anionic complexes [(PNP*)MX] <sup>-</sup>Y<sup>+</sup> (PNP* = double-deprotonated PNP; Y = Li, K) were prepared by deprotonation of the two methylene groups of the corresponding cationic complexes with either 2 equiv of KN(SiMe<sub>3</sub>)<sub>2</sub> or an excess of MeLi. While the reaction of [(PNP)PtCl][Cl] with an excess of MeLi led only to the anionic complex without chloride substitution, reaction of [(PNP)PdCl][Cl] with an excess of MeLi led to the methylated anionic complex [(PNP*)PdMe]<sup>-</sup>Li<sup>+</sup>. NMR studies, X-ray structures, and density functional theory (DFT) calculations reveal that the neutral complexes have a broken aromatic system with alternating single and double bonds, and the deprotonated arm is bound to the ring by an exocyclic CdC double bond. The anionic complexes are best described as a π system comprising the ring carbons conjugated with the exocyclic double bonds of the deprotonated "arms". The neutral complexes are reversibly protonated to their cationic analogues by water or methanol. The thermodynamic parameters.δ H, δ S, and δ G for the reversible protonation of the neutral complexes by methanol were obtained.
Gidron O., Diskin Posner Y. & Bendikov M. (2010) Journal of the American Chemical Society. 132, 7, p. 2148-2150
(Figure Presented) A new type of organic electronic material, consisting of long α-oligofurans containing up to nine rings, was synthesized and characterized. α-Oligofurans are highly fluorescent, with a quantum yield in the range 58-74%. They are more rigid than the corresponding oligothiophenes, with tighter herringbone packing. The calculated twisting energy of oligofurans is significantly higher than that of other conjugated heterocycles. Despite their greater rigidity, oligofurans are more soluble than oligothiophenes. The introduced long oligofurans fulfill the most important requirements for a wide range of applications as organic electronic materials.
Gunanathan C., Diskin Posner Y. & Milstein D. (2010) Crystal Growth & Design. 10, 10, p. 4235-4239
A new lanthanide-organic framework (LOF) based on a long (21.2 Å) and rigid bis-Gd complex synthon (complex 1) and carbonate anion spacers was discovered. Complex 1 is comprised of two Gd<sup>3+</sup> ions complexed with a pyridine tetracarboxylate ligand and a bridging linear 1,4-diethynylbenzene unit. Two water molecules are coordinated to each Gd ion in order to satisfy its high coordination number. Upon crystallization of 1 in ethanolic aqueous sodium bicarbonate, the carbonate anions replace the coordinated water molecules, partially or fully, resulting in the construction of two network types (type A and B). All three oxygen atoms of the carbonate anion are utilized in its function as a spacer between two synthons (complex 1) in the networks, but the chelating oxygen atoms (to Gd<sup>3+</sup> ions) and their coordination modes differ in each of the two networks. In addition, the carbonate anions also serve as acceptors for hydrogen bonding (O-H⋯O) with water molecules coordinated to Gd<sup>3+</sup> ions in both the networks. While all the synthons adopt a planar conformation in network A, they are backed alternatingly in plane and vertical conformation in network B. Overall, in this new LOF the synthons are packed in cris-cross fashion and tethered by carbonate ion spacers, creating a crystal lattice perforated by 10.6 × 15.6 Å and 18.6 × 15.6 Å wide-open channels.
Wijsboom Y. H., Patra A., Zade S. S., Sheynin Y., Li M., Shimon L. L. W. & Bendikov M. (2009) ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 48, 30, p. 5443-5447
Staying on a plane: Even small substituents on the backbone of conjugated polymers can cause them to twist significantly, lowering conjugation and leading to wider band gaps. Oligoand polyselenophenes are more rigid than their thiophene analogues, and can maintain their planarity and low band gap with substituents that otherwise cause considerable twisting. The picture shows two selenophene dimers; Se magenta, S yellow.
Zenkina O. V., Konstantinovski L. E., Shimon L. J. W., Diskin Posner Y., Iron M. A. & van der Boom M. E. (2009) Inorganic Chemistry. 48, 9, p. 4021-4030
Four analogous platinum stilbene- and stilbazole-based complexes exhibit unusual long-range heteronuclear spin-spin coupling in solution. Single crystal analysis and NMR experiments show that the <sup>19</sup>F, <sup>31</sup>P, and <sup>195</sup>Pt nuclei communicate over large distances (0.9-1.3 nm) through bond rather than through space. Spin-spin couplings between <sup>195</sup>Pt and <sup>19</sup>F over seven bonds and between <sup>31</sup>P and <sup>19</sup>F over eight bonds are observed with <sup>7</sup>J<sub>PtF</sub> = 2.9 Hz and <sup>8</sup>J<sub>PF</sub> = 11.8 Hz. Remarkably, a very large spin coupling between <sup>195</sup>Pt and <sup>19</sup>F over six bonds (<sup>6</sup>J <sub>PtF</sub> = 40.1 Hz) is also observed in a structurally related pyridinium complex. Experimental and gNMR (version 5.0) simulated <sup>19</sup>F{ <sup>1</sup>H}, <sup>31</sup>P{<sup>1</sup>H}, and <sup>195</sup>Pt{ <sup>1</sup>H} spectra of the complexes reveal a three-spin AMY system (A = <sup>31</sup>P, M = <sup>31</sup>P, Y = <sup>19</sup>F) or a five-spin AMY3 flanked by a four-spin AMXY or a six-spin AMXY3 system (X = <sup>195</sup>Pt), respectively. Density functional theory calculations at the PBE0/SDD level of theory show a π-conjugated metal-ligand network, which may contribute to the experimentally observed spin-spin interactions.
Voronov-Goldman M., Noach I., Lamed R., Shimon L. J., Borovok I., Bayer E. A. & Frolow F. (2009) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 65, 3, p. 275-278
A cohesin-like module of 160 amino-acid residues from the hypothetical protein AF2375 of the noncellulolytic, hyperthermophilic, sulfate-reducing archaeon Archaeoglobus fulgidus was cloned, expressed, purified, crystallized and subjected to X-ray structural study in order to compare its structure with those of cellulolytic cohesins. The crystals had cubic symmetry, with unit-cell parameters a = b = c = 101.75 Å in space group P4<sub>3</sub>32, and diffracted to 1.82 Å resolution. The asymmetric unit contained a single cohesin molecule. A model assembled from six cohesin structures (PDB entries 1anu, 1aoh, 1g1k, 1qzn, 1zv9 and 1tyj) of very low sequence identity to the cohesin-like module was used in molecular-replacement attempts, producing a marginal solution.
Weiner L., Shin I., Shimon L. J., Miron T., Wilchek M., Mirelman D., Frolow F. & Rabinkov A. (2009) Protein Science. 18, 1, p. 196-205
Alliinase, an enzyme found in garlic, catalyzes the synthesis of the well-known chemically and therapeutically active compound allicin (diallyl thiosulfinate). The enzyme is a homodimeric glycoprotein that belongs to the fold-type I family of pyridoxal-5-phosphate-dependent enzymes. There are 10 cysteine residues per alliinase monomer, eight of which form four disulfide bridges and two are free thiols. Cys368 and Cys376 form a S-S bridge located near the C-terminal and plays an important role in maintaining both the rigidity of the catalytic domain and the substrate-cofactor relative orientation. We demonstrated here that the chemical modification of allinase with the colored-SH reagent N-(4-dimethylamino-3,5-dinitrophenyl) maleimide yielded chromophore-bearing peptides and showed that the Cys220 and Cys350 thiol groups are accesible in solution. Moreover, electron paramagnetic resonance kinetic measurements using disulfide containing a stable nitroxyl biradical showed that the accessibilities of the two -SH groups in Cys220 and Cys350 differ. Neither enzyme activity nor protein structure (measured by circular dichroism) were affected by the chemical modification of the free thiols, indicating that alliinase activity does not require free -SH groups. This allowed the oriented conjugation of alliinase, via the -SH groups, with low- or high-molecular-weight molecules as we showed here. Modification of the alliinase thiols with biotin and their subsequent binding to immobilized streptavidin enabled the efficient enzymatic production of allicin. Published by Wiley-Blackwell.
Zenkina O. V., Karton A., Shimon L. J. W., Martin J. M. L. & van der Boom M. E. (2009) Chemistry-A European Journal. 15, 39, p. 10025-10028
Aryl-halide bond activation and coordination of unsaturated substrates are key steps in many metal-mediated carbon-carbon bond-forming reactions. A series of reactions with stillbenes 1-7 and Pt(PEt<sub>3</sub>)<sub>4</sub> were used to explore the role of substrate coordination on aryl-halide activation. The complexes 8-14 were characterized by NMR spectroscopy, and complexes 9-12 and 14 were isolated and characterized by elemental analysis. Nearly identical spectroscopic properties were reported for structurally related stillbazole complexes. Prolonged reaction times and elevated temperatures resulted in the quantitative formation of complexes 15-21. The X-ray structure of complex 12, confirms the n<sup>2</sup>-coordination of the central carbon-carbon double bond of the stillbene to the metal center. A good linear correlation was observed between the rates of these transformations and the electronic properties of the substituent of the stillbenes.
Frech C. M., Shimon L. J. W. & Milstein D. (2009) Organometallics. 28, 6, p. 1900-1908
The addition of an equimolar amount of hydrochloric acid (-4.0 M in dioxane) to THF solutions of the binuclear Rh(I) complex [(C<sub>10</sub>H <sub>5</sub>(CH<sub>2</sub>Pr<sub>2</sub>)<sub>2</sub>)Rh(η<sup>1</sup>- N<sub>2</sub>)]<sub>2</sub> (1a) at room temperature led to an inseparable mixture of 1a, [(C<sub>10</sub>H<sub>5</sub>(CH<sub>2</sub>PPr<sub>2</sub>) <sub>2</sub>)Rh(Cl)(H)] (2a), and [(C<sub>10</sub>H<sub>5</sub>(CH <sub>2</sub>PPr<sub>2</sub>)<sub>2</sub>)Rh(Cl)<sub>2</sub> (dioxane)], (3a). Exclusive formation of 2a was achieved by slow addition of an equimolar amount of hydrochloric acid (-0.4 M in dioxane) to a THF solution of la at -35 °C, whereas exclusive formation of 3a was obtained when a second equivalent or an excess (-10 equiv) of hydrochloric acid (-4.0 M in dioxane) was added to THF solutions of 2a (or to reaction mixtures, which consist of la, 2a, and 3a). 3a was structurally characterized. In striking difference to the reactivity pattern of la, treatment of THF solutions of the bulky tBu derivative lb with an equimolar amount or even a large excess (-25 equiv) of hydrochloric acid (-4.0 M in dioxane) exclusively yielded the hydrido chloro complex [(C <sub>10</sub>H<sub>5</sub>(CH<sub>2</sub>PBu<sub>2</sub>)<sub>2</sub>)Rh(Cl)(H)] (2b). Chloride abstraction from 2a and 2b with AgBF<sub>4</sub> exclusively yielded the hydrido rhodiurn(ITi) complexes [(C<sub>10</sub>H <sub>5</sub>(CH<sub>2</sub>PR<sub>2</sub>)<sub>2</sub>)Rh(H)(F-BF<sub>3</sub>)] (9a and 9b) with coordination of the counteranion. On the other hand, when an equimolar amount of AgBAr<sup>F</sup><sub>4</sub> was added to methylene chloride (or diethyl ether) solutions of 2a and 2b the cationic, the solvent-stabilized rhodium hydride complexes of type [(C<sub>10</sub>H <sub>5</sub>(CH<sub>2</sub>PR<sub>2</sub>)<sub>2</sub>)Rh(solv)(H)][BAr <sup>F</sup><sub>4</sub>] (10a and 10b) were formed. If the electron density of the metal centers of 9 (and 10) is reduced further by substitution of the coordinated anion of 9 (or the solvent molecule of 10) with a carbonyl ligand, instant migration of the hydride ligand to the aromatic unit toyield the stable carbonyl complexes of type [(C<sub>10</sub>H<sub>5</sub>(CH<sub>2</sub>PR <sub>2</sub>)<sub>2</sub>)<sub>2</sub>(H)Rh(CO)][X] (X = BArF4 11a,11b; X = BF<sub>4</sub>11a ,11b) with η<sup>2</sup> C<sub>ary1</sub>- H agostic interactions was observed. Treatment of 2b with CO gas yielded both isomeric forms of [(C<sub>10</sub>H<sub>5</sub>(CH<sub>2</sub>P'Bu<sub>2</sub>) <sub>2</sub>)Rh(H)(Cl)(CO)] 14b (CO trans to he hydride ligand) and 14b (CO trans to the aromatic pincer core). In contrast, when an excess of CO gas was added to THF (or methylene chloride), solutions of 2a, 14a was exclusively formed within 20 min at room temperature.
Gaviglio C., Ben-David Y., Shimon L. J. W., Doctorovich F. & Milstein D. (2009) Organometallics. 28, 6, p. 1917-1926
Pincer-type linear nitrosyl Rh(I) complexes, Rh(PCPBu)(NO)][BF<sub>4</sub>] (2) and [Rh(PCPBuCH<sub>2</sub>)(NO)][BF,<sub>4</sub>] (8), are reported (PCPBu = 1,3-bis[(di-fer/-butylphosphino)methyl]-2,4,6-trimethylbenzene). Complex 2 was synthesized by reaction of the Rh(I) dinitrogen complex Rh(PCPBu)N <sub>2</sub> (1) with NOBF<sub>2</sub>, while treatment of the methyl chloride complex Rh(PCPBu)(CH<sub>3</sub>)Cl (7) with NOBF<sub>4</sub> led to the formation of 8. Upon addition of CO, a linear bent nitrosyl equilibrium was established, both in solution and in the solid state, between the linear nitrosyl Rh(I) complex 2 and the bent nitrosyl Rh(III) complex [Rh(PCP'Bu)(NO)(CO)][BF<sub>4</sub>] (3). Addition of LiCl to complex 2 resulted in the quantitative formation of the bent nitrosyl complex Rh(PCPBu)(NO)(Cl) (4). An IR study of solvent interactions of the nitrosyl ligand of complex 2 in various solvents is also presented, showing a linear bent nitrosyl equilibrium induced by solvent coordination. Treatment of 4 with HBF<sub>4</sub> · O(C<sub>2</sub>H<sub>5</sub>)<sub>2</sub> led to chloride abstraction, with formation of complex 2. Upon addition of NOBF<sub>4</sub> to the PNP Rh(I) complex [C<sub>5</sub>HN(CH<sub>2</sub>P- (<sup>t</sup>Bu)<sub>2</sub>) <sub>2</sub>Rh(CH<sub>3</sub>CN)]BF<sub>4</sub> (5), the bent nitrosyl complex C<sub>5</sub>H<sub>3</sub>N(CH<sub>2</sub>P(<sup>t</sup>Bu)<sub>2</sub>) <sub>2</sub>Rh(CH<sub>3</sub>CN)(NO)][BF<sub>4</sub>]<sub>2</sub> (6) was obtained. Employing <sup>15</sup>NO-labeled complexes it is possible to assign the bent or linear modes of bonding of NO on the basis of <sup>15</sup>N NMR spectroscopy. X-ray structures of all nitrosyl complexes reported here confirm that the tetracoordinate species are square-planar with a linear nitrosyl ligand occupying the position trans to the aromatic ring and the metal is Rh(I), whereas the pentacoordinate complexes adopt a square-pyramidal geometry with a bent apical nitrosyl coordinated to Rh(III).
Kossoy E., Rybtchinski B., Diskin Posner Y., Shimon L. J. W., Leitus G. & Milstein D. (2009) Organometallics. 28, 2, p. 523-533
Rhodium complexes based on the electron-withdrawing PCP-type pincer ligand dipyrrolylphoshi-noxylene (DPyPX, <sup>Pyr</sup>PCP) were synthesized and their reactivity was studied. Reaction of Rh<sup>I</sup>(<sup>pyr</sup>PCP)PR <sub>3</sub> (2) (R = Et (a). Ph (b); Pyr (pyrrolyl, NC<sub>4</sub>H <sub>4</sub>) (c); Pyd (pyrrolydinyl, NC<sub>4</sub>H<sub>8</sub>) (d)) with MeI was strongly dependent on the sterics and nucleophilicity of PR3. Complex 2a (PEt<sub>3</sub> cone angle, Θ<sup>o</sup>, 132°) reacted with MeI to give isomers of Rh<sup>ΠI</sup>(<sup>Pyr</sup>PCP)Me(I)PEt<sub>3</sub>, 3. Reaction of 2b (Θ<sup>o</sup><sub>PR3</sub> = 145°, R = Pyd (2d), Ph (2b), Pyr (2c)) with MeI was accompanied by release of PPh<sub>3</sub> and is thought to proceed via the 14e intermediate Rh<sup>I</sup>(<sup>Pyr</sup>PCP). While the PPyd<sub>3</sub> complex 2d reacted with MeI to give [Rh <sup>ΠI</sup>(<sup>Pyr</sup>PCP)Me(I)<sub>2</sub>][MePPyd<sub>3</sub>], 4a, the PPyr<sub>3</sub> complex 2c did not react, owing to Steric hindrance around Rh<sup>1</sup> and the low nucleophilicity of PPyr<sub>3</sub>. The aptitude of complexes 2 toward activation of H<sub>2</sub> was also examined. Our results support the involvement of 14e intermediates in the olefin hydrogenation process. The ancillary ligand substitution at the Rh<sup>I</sup> center of 2 was found to proceed by an associative mechanism. ML<sub>5</sub> d<sup>8</sup> intermediates were clearly detected by <sup>31</sup>P{ <sup>1</sup>H} NMR at 213 K during equilibrium between 2a and 2c.
Kohl S. W., Weiner L., Schwartsburd L., Konstantinovski L., Shimon L. J. W., Ben-David Y., Iron M. A. & Milstein D. (2009) Science. 324, 5923, p. 74-77
Discovery of an efficient artificial catalyst for the sunlight-driven splitting of water into dioxygen and dihydrogen is a major goal of renewable energy research. We describe a solution-phase reaction scheme that leads to the stoichiometric liberation of dihydrogen and dioxygen in consecutive thermal- and light-driven steps mediated by mononuclear, well-defined ruthenium complexes. The initial reaction of water at 25°C with a dearomatized ruthenium (II) [Ru(II)] pincer complex yields a monomeric aromatic Ru(II) hydrido-hydroxo complex that, on further reaction with water at 100°C, releases H2 and forms a cis dihydroxo complex. Irradiation of this complex in the 320-to-420-nanometer range liberates oxygen and regenerates the starting hydrido-hydroxo Ru(II) complex, probably by elimination of hydrogen peroxide, which rapidly disproportionates. Isotopic labeling experiments with H <sub>2</sub> <sup>17</sup>O and H<sub>2</sub> <sup>18</sup>O show unequivocally that the process of oxygen-oxygen bond formation is intramolecular, establishing a previously elusive fundamental step toward dioxygen-generating homogeneous catalysis.
Salem H., Shimon L. J. W., Diskin Posner Y., Leitus G., Ben-David Y. & Milstein D. (2009) Organometallics. 28, 16, p. 4791-4806
The synthesis of a series of new ruthenium complexes based on the new PONOP ligands 1 and 10 ((C<sub>5</sub>H<sub>3</sub>N-1,3-(OPR<sub>2</sub>) <sub>2</sub>: 1, R = <sup>i</sup>Pr; 10, R = <sup>t</sup>Bu) is presented, including the stable trans-dihydride complexes (<sup>i</sup>Pr-PONÖP)Ru(H) <sub>3</sub>(PPh<sub>3</sub>) (4) and (rBu-PONOP)Ru(H)<sub>2</sub>(CO) (12) and the stable Ru(0) complexes (R-PONOP)Ru(CO)<sub>2</sub> (6, R = <sup>i</sup>Pr; 15, R = <sup>t</sup>Bu). A surprisingly stable 16-electron Ru(0) complex (13) was formed by deprotonation of 12 with KO<sup>t</sup>Bu. Complex 13 reacts with H<sub>2</sub> to afford the cis-dihydride complex 12a, which isomerized to the trans-dihydride 12. Complex 13 reacted with CO to afford the saturated Ru(0) complex 15. Reaction of complex 12 with water led to hydrolysis of the phosphinite PONOP ligand and rearrangement to a dimeric product (14). Reaction of the trans-dihydride complex 4 with the electrophiles PhCOCl, Mel, and MeOTf led to abstraction of one of the hydride ligands, forming the monohydride complexes (<sup>i</sup>Pr-PONOP)Ru(H)(PPh<sub>3</sub>)(X) (X = Cl (2), I (8a), OTf (8b)) together with benzaldehyde in the case of 2. Similarly, 12 afforded the monohydride complexes (<sup>t</sup>Bu-PONOP)Ru(H)(CO)(X) (X = Cl (11), OTf (17), I (18)). Reaction of the Ru(0) complexes 6 and 15 with water resulted in hydrolysis of the O - P bond and formation of the zwitterionic complexes 7 and 16. Treatment of 2 and 11 with MeOTfor Mel resulted in abstraction of the chloride ligand rather than the hydride, forming complexes 8a, b and 17, 18, respectively. Additional syntheses of complexes based on ligands 1 and 10 are presented.
Noach I., Frolow F., Alber O., Lamed R., Shimon L. J. & Bayer E. A. (2009) Journal of Molecular Biology. 391, 1, p. 86-97
Cellulosome complexes comprise an intercalated set of multimodular dockerin-containing enzymatic subunits connected to cohesin-containing nonenzymatic subunits called scaffoldins. The adjoining modules in each cellulosomal subunit are interconnected by a variety of linker segments of different lengths and composition. The exact role of the cellulosomal linkers has yet to be described, although it is assumed that they contribute to the architecture and action of the cellulosome by providing the protein subunits with flexibility and by providing spacers between the enzymatic modules that could enhance interactions with the cellulose substrate. Here we present four crystal structures of Acetivibrio cellulolyticus cellulosomal type II cohesins with linker extensions. Two of the structures represent two different crystal forms (trigonal and orthorhombic) of the same N-terminal cohesin module (CohB1) together with its full (6-residue) native C-terminal linker, derived from scaffoldin B. The other two structures belong to the adjacent (second) cohesin module (CohB2), each of which was crystallized with the same 6-residue linker segment, but now positioned at the N-terminus and with either a truncated (5-residue) or a full-length (45-residue) C-terminal linker, respectively. Comparison between the two CohB1 structures revealed significant differences in the conformation of their equivalent C-terminal linker segment. In one crystal form a helical conformation was observed, as opposed to an extended conformation in the other. The CohB2 structures also displayed diverse conformations in their linker segments. In these structures, different linker conformations were observed in the individual molecules within the asymmetric unit of each structure. This conformational diversity implies that the linkers may adopt alternative conformations in their natural environment, consistent with varying environmental conditions. The findings suggest that linkers can play an important role in the assembly, dynamics and function of the cellulosomal components.
Gunanathan C., Shimon L. J. W. & Milstein D. (2009) Journal of the American Chemical Society. 131, 9, p. 3146-3147
The crystallographically characterized ruthenium complex RuHCl(A-Pr-PNP)(CO) (1) [A-'Pr-PNP = 4,5-bis-(diisopropylphosphinomethyl) acridine], which bears a nonplanar acridine moiety, catalyzes in a neutral medium the transformation of primary alcohols to the corresponding acetals with the liberation of H<sub>2</sub>. In the presence of base, complex 1 catalyzes the dehydrogenative coupling of alcohols to form esters. Acetal formation may involve hemiacetal dehydration to form an enol ether followed by alcohol addition to the double bond.
Suad O., Rozenberg H., Brosh R., Diskin Posner Y., Kessler N., Shimon L. J. W., Frolow F., Liran A., Rotter V. & Shakked Z. (2009) Journal of Molecular Biology. 385, 1, p. 249-265
The tumor suppressor protein p53 is mutated in more than 50% of invasive cancers. About 30% of the mutations are found in six major "hot spot" codons located in its DNA binding core domain. To gain structural insight into the deleterious effects of such mutations and their rescue by suppressor mutations, we determined the crystal structures of the p53 core domain incorporating the hot spot mutation R249S, the core domain incorporating R249S and a second-site suppressor mutation H168R (referred to as the double mutant R249S/H168R) and its sequence-specific complex with DNA and of the triple mutant R249S/H168R/T123A. The structural studies were accompanied by transactivation and apoptosis experiments. The crystal structures show that the region at the vicinity of the mutation site in the R249S mutant displays a range of conformations [wild-type (wt) and several mutant-type conformations] due to the loss of stabilizing interactions mediated by R249 in the wt protein. As a consequence, the protein surface that is critical to the formation of functional p53-DNA complexes, through protein-protein and protein-DNA interactions, is largely distorted in the mutant conformations, thus explaining the protein's "loss of function" as a transcription factor. The structure of this region is restored in both R249S/H168R and R249S/H168R/T123A and is further stabilized in the complex of R249S/H168R with DNA. Our functional data show that the introduction of H168R as a second-site suppressor mutation partially restores the transactivation capacity of the protein and that this effect is further amplified by the addition of a third-site mutation T123A. These findings together with previously reported data on wt and mutant p53 provide a structural framework for understanding p53 dysfunction as a result of oncogenic mutations and its rescue by suppressor mutations and for a potential drug design aimed at restoring wt activity to aberrant p53 proteins.
Ebralidze I. I., Leitus G., Shimon L. J. & Neumann R. (2009) Inorganica Chimica Acta. 362, 13, p. 4760-4766
Reaction of nickel (II) perchlorate with the ligand N,N-bis-(3,5-dipiperidin-1-yl-[2,4,6]triazin-1-yl)-pyridin-2-ylmethyl-ethane-1,2-diamine yields an octahedral Ni(II) high-spin complex 1 ([C<sub>40</sub>H<sub>56</sub>N<sub>14</sub>Ni(H<sub>2</sub>O)(CH<sub>3</sub>OH)](ClO<sub>4</sub>)<sub>2</sub>(CH<sub>3</sub>OH)<sub>2</sub>) with moderate zero-field splitting (ZFS) axial distortion parameter D/k<sub>B</sub> = 5.37 K. The ligand contributes a N4 donor set; the remaining two coordinating positions are occupied by coordinating solvents molecules. Exchange of the coordinating solvents molecules in complex 1 to thiocyanate moieties leads to formation of complex 2 ([C<sub>40</sub>H<sub>56</sub>N<sub>14</sub>Ni(NCS)<sub>2</sub>](CHCl)<sub>3</sub>) with an extended parameter D/k<sub>B</sub> = 8.80 K. The analysis of the structural and magnetic properties of complexes 1 and 2 led to the design of dinuclear complex 3 ([C<sub>40</sub>H<sub>56</sub>N<sub>14</sub>NiN<sub>3</sub>]<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub>(CH<sub>3</sub>OH)<sub>2</sub>), where two azido groups were utilized as bridging ligands. The double azido bridges in complex 3 cross each other to form a rarely observed non-coplanar (N<sub>3</sub>)<sub>2</sub> structure. The magnetic behavior of complex 3 reveals ferromagnetic coupling interactions characterized by J/k<sub>B</sub> = 23.25 K, D<sub>1</sub>/k<sub>B</sub> = 7.90 K, D<sub>2</sub>/k<sub>B</sub> = 0.54 K.
Alber O., Noach I., Rincon M. T., Flint H. J., Shimon L. J., Lamed R., Frolow F. & Bayer E. A. (2009) Proteins-Structure Function And Bioinformatics. 77, 3, p. 699-709
The cellulosome is an intriguing multienzyme complex found in cellulolytic bacteria that plays a key role in the degradation of plant cell-wall polysaccharides. In Ruminococcus flavefaciens, a predominant fiber-degrading bacterium found in ruminants, the cellulosome is anchored to the bacterial cell wall through a relatively short ScaE scaffoldin. Determination of the crystal structure of the lone type-III ScaE cohesin from R. flavefaciens (Rf-CohE) was initiated as a part of a structural effort to define cellulosome assembly. The structure was determined at 1.95 Å resolution by single-wavelength anomalous diffraction. This is the first detailed description of a crystal structure for a type-III cohesin, and its features were compared with those of the known type-I and type-II cohesin structures. The Rf-CohE module folds into a ninestranded β-sandwich with jellyroll topology, typically observed for cohesins, and includes two β-flaps in the midst of β-strands 4 and 8, similar to the type-II cohesin structures. However, the presence in Rf-CohE of an additional 13-residue a-helix located between β-strands 8 and 9 represents a dramatic divergence from other known cohesin structures. The prominent α-helix is enveloped by an extensive N-terminal loop, not observed in any other known cohesin, which embraces the helix presumably enhancing its stability. A planar surface at the upper portion of the front face of the molecule, bordered by β-flap 8, exhibits plausible dimensions and exposed amino acid residues to accommodate the dockerin-binding site.
Ebralidze I. I., Leitus G., Shimon L. J., Wang Y., Shaik S. & Neumann R. (2009) Inorganica Chimica Acta. 362, 13, p. 4713-4720
Manganese(II) complexes, Mn<sub>2</sub>L<sup>1</sup><sub>3</sub>(ClO<sub>4</sub>)<sub>4</sub>, MnL<sup>1</sup>(H<sub>2</sub>O)<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub>, MnL<sup>2</sup>(H<sub>2</sub>O)<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub>, and {(μ-Cl)MnL<sup>2</sup>(PF<sub>6</sub>)}<sub>2</sub> based on N,N-bis(2-pyridinylmethylene) ethanediamine (L<sup>1</sup>) and N,N-bis(2-pyridinylmethylene) propanediamine (L<sup>2</sup>) ligands have been prepared and characterized. The single crystal X-ray diffraction analysis of Mn<sub>2</sub>L<sup>2</sup><sub>3</sub>(ClO<sub>4</sub>)<sub>4</sub> shows that each of the two Mn(II) ion centers with a Mn-Mn distance of 7.15 Å are coordinated by one ligand while a common third ligand bridges the metal centers. Solid-state magnetic susceptibility measurements as well as DFT calculations confirm that each of the manganese centers is high-spin S = 5/2. The electronic structure obtained shows no orbital overlap between the Mn(II) centers indicating that the observed weak antiferromagentism is a result of through space interactions between the two Mn(II) centers. Under different reaction conditions, L<sup>1</sup> and Mn(II) yielded a one-dimensional polymer, MnL<sup>1</sup>(H<sub>2</sub>O)<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub>. Ligand L<sup>2</sup> when reacted with manganese(II) perchlorate gives contrarily to L<sup>1</sup> mononuclear MnL<sup>2</sup>(H<sub>2</sub>O)<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub> complex. The analysis of the structural properties of the MnL<sup>2</sup>(H<sub>2</sub>O)<sub>2</sub>(ClO<sub>4</sub>)<sub>2</sub> lead to the design of dinuclear complex {(μ-Cl)MnL<sup>2</sup>(PF<sub>6</sub>)} where two chlorine atoms were utilized as bridging moieties. This complex has a rhomboidal Mn<sub>2</sub>Cl<sub>2</sub> core with a Mn-Mn distance of 3.726 Å. At room temperature {(μ-Cl)MnL<sup>2</sup>(PF<sub>6</sub>)} is ferromagnetic with observed μ<sub>eff</sub> = 4.04 μ<sub>B</sub> per Mn(II) ion. With cooling, μ<sub>eff</sub> grows reaching 4.81 μ<sub>B</sub> per Mn(II) ion at 8 K, and then undergoes ferromagnetic-to-antiferromagnetic phase transition.
Alber O., Noach I., Lamed R., Shimon L. J., Bayer E. A. & Frolow F. (2008) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 64, 2, p. 77-80
Ruminococcus flavefaciens is an anaerobic bacterium that resides in the gastrointestinal tract of ruminants. It produces a highly organized multi-enzyme cellulosome complex that plays a key role in the degradation of plant cell walls. ScaE is one of the critical structural components of its cellulosome that serves to anchor the complex to the cell wall. The seleno-l-methionine-labelled derivative of the ScaE cohesin module has been cloned, expressed, purified and crystallized. The crystals belong to space group C2, with unit-cell parameters a = 155.6, b = 69.3, c = 93.0 Å, β = 123.4°, and contain four molecules in the asymmetric unit. Diffraction data were phased to 1.95 Å using the anomalous signal from the Se atoms.
Zhang J., Gandelman M., Shimon L. J. W. & Milstein D. (2008) Organometallics. 27, 14, p. 3526-3533
The choice of synthetic methodology leads to either carbene or diazoalkane complexes of the same system. Thus, treatment of RuCl<sub>2</sub>(PPh <sub>3</sub>)<sub>3</sub> with 9-diazofluorene followed <sup>t</sup>Bu-PNP (<sup>t</sup>Bu-PNP = 2,6-bis(diiert-butylphosphinomethyl)pyridine) resulted in loss of dinitrogen and formation of the Ru(II) fluorenylidene complex 1. On the other hand, treatment of the <sup>t</sup>Bu-PNP Ru(II) dinitrogen complex 4 with 9-diazofluorene resulted in the formation of η<sup>1</sup>-dizaofluorene Ru(II) complex 5, in which the diazo unit remains intact. The cationic Ru(II) carbene complex 2 was obtained by the reaction of 1 with 1 equiv of AgBF <sub>4</sub> or HBF<sub>4</sub>. Chloride dissociation to form a 16-e cationic carbene complex 3 took place also upon refluxing of 1 in toluene. The five-coordinated, unsaturated, charge-neutral diiodide Ru(II) complex 6 was obtained by reaction of 4 with NaI. Complex 6 is stabilized by a C-H agostic interaction, as observed by X-ray crystallography. Reaction of 4 with NaBEt3H followed by 9-dizaofluorene resulted in a novel η<sup>1</sup>- diazenofluorene Ru(II) complex 7, accompanied by the migration of one hydrogen atom from the metal center to the coordinated nitrogen atom of the diazenofluorene unit. Heating complex 7 at 65°C resulted in sp<sup>2</sup> C-H activation followed by elimination of dihydrogen to form the chelated, β-carbon coordinated diazenofluorene ruthenium complex 8. Complexes 1, 2, 5, 6, and 8 were structurally characterized by X-ray crystallography.
Vuzman D., Poverenov E., Shimon L. J. W., Diskin Posner Y. & Milstein D. (2008) Organometallics. 27, 11, p. 2627-2634
The synthesis and reactivity of new Pt(II) complexes, including anionic d<sup>8</sup> complexes, based on the electron-rich, hemilabile PNN-type pincer ligand C<sub>5</sub>H<sub>3</sub>N-2-(CH<sub>2</sub>P<sup>t</sup>Bu <sub>2</sub>)(CH<sub>2</sub>NEt<sub>2</sub>) are described. Formation of these complexes involves dearomatization/aromatization processes of the ligand. The chloride complex [(PNN)PtCl]<sup>+</sup>Cl<sup>-</sup> (1) was prepared and reacted with the base <sup>t</sup>BuOK to give the deprotonated, neutral chloride complex (PNN*)PtCl (2) (PNN* = C<sub>5</sub>H <sub>3</sub>N-2-(CHP<sup>t</sup>Bu<sub>2</sub>)(CH<sub>2</sub>NEt<sub>2</sub>)). Reaction of 2 with <sup>n</sup>BuLi gave the corresponding neutral hydride complex (PNN*)PtH (3), which was readily protonated by triflic acid to give the cationic hydride complex [(PNN)PtH]<sup>+</sup>OTf<sup>-</sup> (4). Unexpectedly, reaction of complex 2 with 1 equiv of RLi resulted in opening of the chelate ring, to give the corresponding anionic, dearomatized complexes Li<sup>+</sup>[(PNN*)Pt(Cl)(R)]<sup>-</sup> (R = methyl, 5; phenyl, 6). Notably, these complexes are relatively stable although they bear no stabilizing π acceptors that can lower the electron density at the metal center. Complexes 5 and 6 readily undergo protonation by HCl to form the corresponding neutral, aromatic complexes (PNN)Pt(Cl)(R) (R = methyl, 7; phenyl, 8), in which the hemilabile amine "arm" remains decoordinated and does not undergo protonation. Minor amounts of the dearomatized chloride complex 2 are also formed as a result of elimination of RH. Reaction of complexes 5 and 6 with water results in selective protonation-aromatization to give the corresponding complexes 7 and 8.
Vartanian M., Lucassen A. C. B., Shimon L. J. W. & van der Boom M. E. (2008) Crystal Growth & Design. 8, 3, p. 786-790
Two cocrystals (4, 5) have been obtained with 1,3,5-tris[4-pyridyl(ethenyl) ]benzene (1), sym-triiodo-trifluorobenzene (2), and diiodo-tetrafluorobenzene (3), respectively. Cocrystal 4 contains both compounds 1 and 2 in a molecular ratio of 1:2, whereas cocrystal 5 contains both compounds 1 and 3 in a molecular ratio of 1:0.5 and the solvent used for crystallization, namely, chloroform. Both cocrystals (4, 5) contain N⋯I halogen bonds with distances of ∼80% of the sum of the van der Waals radii. Compound 1 forms four halogen bonding interactions in cocrystal 4, resulting in an infinite halogen-bonded network with two types of N⋯I halogen bonds, whereas in cocrystal 5, compound 1 forms only one type of halogen bonding interaction with compound 3.
Zenkina O. V., Karton A., Freeman D., Shimon L. J. W., Martin J. M. L. & van der Boom M. E. (2008) Inorganic Chemistry. 47, 12, p. 5114-5121
Activation of a strong aryl-Br bond of a halogenated vinylarene by nickel(0) is demonstrated in the presence of aryl-I containing substrates. η<sup>2</sup>-Coordination of Ni(PEt<sub>3</sub>)<sub>2</sub> to the C=C moiety of halogenated vinylarenes is kinetically preferable and is followed by an intramolecular aryl-halide bond activation process. This "ring- walking" process is quantitative and proceeds under mild reaction conditions in solution. Mechanistic studies indicate that the metal insertion into the aryl-halide bond is not the rate-determining step. The reaction obeys first-order kinetics in the η<sup>2</sup>-coordination complexes with almost identical activation parameters for Br and I derivatives. The ring-walking process is kinetically accessible as shown by density functional theory (DFT) calculations at the PBE0/SDB-cc-pVDZ//PBE0/SDD level of theory.
Zenkina O. V., Konstantinovski L., Freeman D., Shimon L. J. W. & van der Boom M. E. (2008) Inorganic Chemistry. 47, 9, p. 3815-3822
The fluxional behavior of two analogous platinum complexes has been studied in solution by NMR spectroscopy to elucidate the reaction mechanism and to determine the activation parameters. This includes variable temperature NMR spectroscopy, 2D <sup>1</sup>H-<sup>1</sup>H exchange spectroscopy, and spin saturation transfer measurements. A platinum moiety, Pt(PEt<sub>3</sub>) <sub>2</sub>, translocates between two carbon-carbon double bonds of two vinylpyridine moieties bridged by an arene (i.e., phenyl, anthracene) at elevated temperatures. Magnetization transfer NMR experiments in the presence of free ligands unambiguously revealed an intramolecular pathway for the "phenyl" system. An intermolecular pathway is proposed for the "anthracene" complex.
Salem H., Shimon L. J. W., Leitus G., Weiner L. & Milstein D. (2008) Organometallics. 27, 10, p. 2293-2299
A rare case of BAr<sub>F</sub> anion cleavage (BAr<sub>F</sub><sup>-</sup> = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) by a metal complex is described. Reaction of the Rh(I) dinitrogen complexes 5a,b and 6a,b, based on the phosphinite pincer ligands {C<sub>6</sub>H<sub>4</sub>[OP( <sub>t</sub>Bu)<sub>2</sub>]<sub>2</sub>} (2), with 2 equiv of AgBAr<sub>F</sub> at room temperature resulted in B-C bond cleavage of one of the BAr<sub>F</sub> anions and aryl transfer to afford the Rh(III) aryl complexes 7 and 8, respectively. The X-ray structure of 8 revealed a square-pyramidal geometry with a coordinated acetone molecule. The aryl transfer occurred as a result of electrophilic attack by unsaturated Rh(III) on one of the aryl rings of the BAr<sub>F</sub> anion. Utilizing different solvents yielded the same product, except when CH<sub>3</sub>CN was used, in which case one-electron oxidation took place, yielding complex 9. Treatment of 6a,b with 1 equiv of AgX (X = BAr <sub>F</sub>, BF<sub>4</sub>, PF<sub>6</sub>) resulted in a one-electron oxidation to yield the paramagnetic Rh(II) complexes 9-11, respectively. Complex 11 was characterized by X-ray diffraction, revealing a mononuclear square-planar Rh(II) complex.
Shirman T., Lamere J., Shimon L. J. W., Gupta T., Martin J. M. L. & van der Boom M. E. (2008) Crystal Growth & Design. 8, 8, p. 3066-3072
A series of phenylethynyl pyridine derivatives 1-4 possessing both perfluorocarbon (PFC) and hydrocarbon (HC) moieties have been synthesized and used for the formation of halogen bonding (XB)-based networks. X-ray crystal structure analyses indicate the dominance of XB synthons, which represent the one-dimensional (ID) structure directing interaction, leading to the formation of supramolecular chains. The influence of structural/electronic factors (e.g., electron donor/acceptor strength, sterically demanding substituents) on XB formation of compounds 1-4 have been compared with structurally related stilbazole systems (I, II). The XB-bonded networks are formed in collaboration with other noncovalent interactions such as π-π stacking, hydrogen bonding, C-H⋯F and F⋯F. Molecular electrostatic potentials and atomic polar tensor (APT) charges of the donor and acceptor sites have been determined by density functional theory (DFT) calculations.
Klerman Y., Ben-Ari E., Diskin Posner Y., Leitus G., Shimon L. J. W., Ben-David Y. & Milstein D. (2008) Dalton Transactions. 2008, 24, p. 3226-3234
The cationic, pincer-type complexes [(SNS)Ir(COE)][BF<sub>4</sub>] (1) and [(SNS)Rh(COE)][BF<sub>4</sub>] (2) (SNS = 2,6-bis(t-butylthiomethy1)pyridine; COE = cyclooctene) complexes were prepared, and their structure and reactivity were studied. They are fluxional at room temperature as a result of "arm" hemilability, which can be frozen at low temperatures. Reaction of complex 1 with H<sub>2</sub> resulted in a dimeric dihydride complex [(SNS)Ir(H<sub>2</sub>)]<sub>2</sub>[BF<sub>4</sub>]<sub>2</sub> (3) in which the sulfur atoms bridge between two metal centers. The Rh complex 2 did not react with H<sub>2</sub>. Both the carbonyl complexes [(SNS)Ir(CO)][BF <sub>4</sub>] (5) and [(SNS)Rh(CO)][BF<sub>4</sub>] (6) show differences in the IR stretching frequencies in solution vs. solid states, which are a result of uncommon metal-metal interactions between square planar d<sup>8</sup> systems in the solid state. Complexes 1, 3, 5 and 6 were structurally characterized by X-ray crystallography. A network of hydrogen bonds involving the BF <sub>4</sub><sup>-</sup> counter anion and hydrogen atoms of complex 5 was observed.
Montag M., Efremenko I., Cohen R., Leitus G., Shimon L. J. W., Diskin Posner Y., Ben-David Y., Martin J. M. L. & Milstein D. (2008) Chemistry - A European Journal. 14, 27, p. 8183-8194
The crystal structure of the new cation ic Rh<sup>1</sup> complex trans-[Rh(CO)<sub>2</sub>(L)<sub>2</sub>]BF<sub>4</sub> (L = a <sup>2</sup>-(diisopropylphosphino)isodurene) was found to exhibit a nonlinear OC-Rh-CO fragment and weak intramolecular C-H⋯Rh interactions. These interactions, which have also been shown to occur in solution, have been examined by density functional theory calculations and found to be inextricably linked to the presence of the distorted OC-Rh-CO fragment. This linkage has also been demonstrated by comparison with a highly similar Rh<sup>I</sup> complex, in which these C-H⋯Rh interactions are absent. Furthermore, the presence of these weak interactions has been shown to have a significant effect on the reactivity of the metal center.
Perissinotti L. L., Leitus G., Shimon L., Estrin D. & Doctorovich F. (2008) Inorganic Chemistry. 47, 11, p. 4723-4733
In this work, we present a complete and detailed experimental characterization and theoretical study of a variety of coordinated S-nitrosothiols (RSNOs), such as cysteine derivatives, mercaptosuccinic acid, benzyl thiol, and phenyl thiol. Some of them are extremely unstable and sensitive in free form. Strikingly, in contrast with free S-nitrosothiols, we found that, upon coordination to iridium, they become very stable even in aqueous solutions. The study of these coordinated complexes provides further insight on the elucidation of structural aspects dealing with the nature of the S-N bond in RSNOs, a fact which still remains a matter of controversy.
Noach I., Alber O., Bayer E. A., Lamed R., Levy-Assaraf M., Shimon L. J. & Frolow F. (2008) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 64, 1, p. 58-61
The second type II cohesin module of the cellulosomal scaffoldin polypeptide ScaB from Acetivibrio cellulolyticus (CohB2) was cloned into two constructs: one containing a short (five-residue) C-terminal linker (CohB2_S) and the second incorporating the full native 45-residue linker (CohB2_L). Both constructs encode proteins that also include the full native six-residue N-terminal linker. The CohB2_S and CohB2_L proteins were expressed, purified and crystallized in the orthorhombic crystal system, but with different unit cells and symmetries: space group P2<sub>1</sub>2<sub>1</sub>2<sub>1</sub> with unit-cell parameters a = 90.36, b = 68.65, c = 111.29 Å for CohB2_S and space group P2<sub>1</sub>2<sub>1</sub>2 with unit-cell parameters a = 68.76, b = 159.22, c = 44.21 Å for CohB2_L. The crystals diffracted to 2.0 and 2.9 Å resolution, respectively. The asymmetric unit of CohB2_S contains three cohesin molecules, while that of CohB2_L contains two molecules.
Paraskar A. S., Ravikumar Reddy A., Patra A., Wijsboom Y. H., Gidron O., Shimon L. J., Leitus G. & Bendikov M. (2008) Chemistry-A European Journal. 14, 34, p. 10639-10647
Surprisingly, despite its very high mobility in a single crystal, rubrene shows very low mobility in vacuum-sublimed or solution-processed organic thin-film transistors. We synthesized several rubrene analogues with electron-withdrawing and electron-donating substituents and found that most of the substituted rubrenes are not planar in the solid state. Moreover, we conclude (based on experimental and calculated data) that even parent rubrene is not planar in solution and in thin films. This discovery explains why high mobility is reported in rubrene single crystals, but rubreneshows very low field-effect mobility in thin films. The substituted rubrenes obtained in this work have significantly better solubility than parent rubrene and some even form films and not crystals after evaporation of the solvent. Thus, substituted rubrenes are promising materials for organic light-emitting diode (OLED) applications.
Schaub T., Radius U., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2008) Organometallics. 27, 8, p. 1892-1901
The new pyridine-based sulfoxide pincer ligand 1 (2-(diethylaminomethyl)-6- (tert-butylsulfinylmethyl)pyridine = S(O)NN) reacts cleanly with Rh <sub>2</sub>(COE)<sub>4</sub>Cl<sub>2</sub> to form the neutral water- and air-stable Rh<sup>1</sup> complex [Rh(S(O)NN)(NCCH<sub>3</sub>)], 1. The cationic complexes [Rh(S(O)NN(NCCH<sub>3</sub>)][BF<sub>4</sub>] (2) and [Ir(S(O)NN)(COE)][BF<sub>4</sub>] (5) were obtained by the reaction of 1 with the appropriate metal precursors. The corresponding carbonyl complexes [Rh(S(O)NN)(CO)][PF<sub>6</sub>] (4) and [Ir(S(O)NN)(CO)][BF<sub>4</sub>] (7) exhibit vCO in the IR spectra that shows that ligand 1 is a relatively poor a-donor ligand compared to the more common PNP-type ligands, resulting in rather electron-poor metal centers. The carbonyl compounds can be deprotonated to the remarkably stable dearomatized complexes Rh(S(O)NN*)(CO) (8) and Ir(S(O)NN*)(CO) (9). DFT studies on 8 revealed a high electron derealization over the pyridine ring system and the sulfur atom, which explains the high stability of 8 toward reprotonation. Complete protonation of 8 was achieved in acetic acid.
Goihberg E., Dym O., Tel-Or S., Shimon L., Frolow F., Peretz M. & Burstein Y. (2008) Proteins-Structure Function And Bioinformatics. 72, 2, p. 711-719
Analysis of the three-dimensional structures of two closely related thermophilic and hyperthermophilic alcohol dehydrogenases (ADHs) from the respective microorganisms Entamoeba histolytica (EhADH1) and Thermoanaerobacter brockii (TbADH) suggested that a unique, strategically located proline residue (Pro275) at the center of the dimerization interface might be crucial for maintaining the thermal stability of TbADH. To assess the contribution of Pro275 to the thermal stability of the ADHs, we applied site-directed mutagenesis to replace Asp275 of EhADH1 with Pro (D275P-EhADH1) and conversely Pro275 of TbADH with Asp (P275D-TbADH). The results indicate that replacing Asp275 with Pro significantly enhances the thermal stability of EhADH1 (ΔT<sub>1/2</sub> ≤ + 10°C), whereas the reverse mutation in the thermophilic TbADH (P275D-TbADH) reduces the thermostability of the enzyme (ΔT<sub>1/2</sub> ≤ -18.8°C). Analysis of the crystal structures of the thermostabilized mutant D275P-EhADH1 and the thermocompromised mutant P275D-TbADH suggest that a proline residue at position 275 thermostabilized the enzymes by reducing flexibility and by reinforcing hydrophobic interactions at the dimer-dimer interface of the tetrameric ADHs.
Korshin E. E., Leitus G., Shimon L. J. W., Konstantinovski L. & Milstein D. (2008) Inorganic Chemistry. 47, 16, p. 7177-7189
Aiming at the generation of a silanone intramolecularly bound to platinum, we prepared pincer-type PSiP silanol Pt(II) complexes. While a stable silanone complex was not isolated, unusual reactivity modes, involving its possible intermediacy, were observed. Treatment of the new PSiH<sub>2</sub>P-type ligand (o-iPr<sub>2</sub>PC<sub>6</sub>H<sub>4</sub>)<sub>2</sub>SiH<sub>2</sub> (7) with (Me<sub>2</sub>S)<sub>2</sub>Pt(Me)Cl yields the pincer-type hydrosilane complex [{(o- iPr<sub>2</sub>PC<sub>6</sub>H<sub>4</sub>)<sub>2</sub>SiH}PtCl] (8), which upon Ir(I)-catalyzed hydrolytic oxidation gives the structurally characterized silanol complex [{(o- iPr<sub>2</sub>PC<sub>6</sub>H <sub>4</sub>)<sub>2</sub>SiOH}PtCl] (3). Complex 3, comprising in its structure the nucleophilic silanol fragment and electrophilic Pt(II)-Cl moiety, exhibits dual reactivity. Its reaction with the non-nucleophilic KB(C<sub>6</sub>F <sub>5</sub>)<sub>4</sub> in fluorobenzene leads to the ionic complex [{(o- iPr<sub>2</sub>PC<sub>6</sub>H<sub>4</sub>)<sub>2</sub>SiOH}Pt]<sup>+</sup> [(C<sub>6</sub>F<sub>5</sub>)<sub>4</sub>B]<sup>-</sup> (9), which reacts with CO to yield the structurally characterized [{(o- iPr<sub>2</sub>PC <sub>6</sub>H<sub>4</sub>)<sub>2</sub>SiOH}PtCO]<sup>+</sup> [(C <sub>6</sub>F<sub>5</sub>)<sub>4</sub>B]<sup>-</sup> (10). Treatment of 3 with non-nucleophilic bases leads to unprecedented rearrangement and coupling, resulting in the structurally characterized, unusual binuclear complex 11. The structure of 11 comprises two different fragments: the original O-Si-Pt(II)-Cl pattern, and the newly formed silanolate Pt(II)-H pattern, which are connected via a disiloxane bridge. Complex 9 undergoes a similar hydrolytic rearrangement in the presence of iPr<sub>2</sub>NEt to give the mononuclear silanolate Pt(II)-H complex 17. Both these rearrangement-coupling reactions probably involve the inner-sphere generation of an intermediate silanone 14, which undergoes nucleophilic attack by the starting silanol 3 to yield complex 11, or adds a water molecule to yield complex 17. X-ray diffraction studies of 3, 10, and 11 exhibit a very short Si-Pt bond length (2.27-2.28 Å) in the neutral complexes 3 and 11 that elongates to 2.365 Å in the carbonyl complex 10. A significantly compressed geometry of the silanolate platinum(II)-hydride fragment B of the binuclear complex 11 features a Pt(2)-O(2)-Si(2) angle of 100.4 (3)° and a remarkably short Pt(2)⋯Si(2) [2.884 (3) Å] distance.
Poverenov E., Efremenko I., Frenkel A. I., Ben-David Y., Shimon L. J. W., Leitus G., Konstantinovski L., Martin J. M. L. & Milstein D. (2008) Nature. 455, 7216, p. 1093-1096
Terminal oxo complexes of transition metals have critical roles in various biological and chemical processes. For example, the catalytic oxidation of organic molecules, some oxidative enzymatic transformations, and the activation of dioxygen on metal surfaces are all thought to involve oxo complexes. Moreover, they are believed to be key intermediates in the photocatalytic oxidation of water to give molecular oxygen, a topic of intensive global research aimed at artificial photosynthesis and water splitting. The terminal oxo ligand is a strong π-electron donor, so it readily forms stable complexes with high-valent early transition metals. As the d orbitals are filled up with valence electrons, the terminal oxo ligand becomes destabilized. Here we present evidence for a d<sup>n</sup> (n > 5) terminal oxo complex that is not stabilized by an electron withdrawing ligand framework. This d<sup>6</sup> Pt(iv) complex exhibits reactivity as an inter- and intramolecular oxygen donor and as an electrophile. In addition, it undergoes a water activation process leading to a terminal dihydroxo complex, which may be relevant to the mechanism of catalytic reactions such as water oxidation.
Barats D., Leitus G., Popovitz-Biro R., Shimon L. J. W. & Neumann R. (2008) ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 47, 51, p. 9908-9912
(Figure presented) Head over EELS: Reaction of O<sub>2</sub> with a hexa-iron(II)-substituted polyoxometalate in water yields a polyoxometalate with "end-on" hydroperoxo groups, {Fe<sup>III</sup>-O<sub>2</sub>H}, at the terminal positions. The hydroperoxo moiety, stabilized by hydrogen bonding with water, is unusual for its long O-O bond and nearly linear Fe-O-O bond angle. Electron energy-loss spectroscopy (EELS) is used to determine the oxidation state of iron.
Ebralidze I. I., Leitus G., Shimon L. J. W. & Neumann R. (2008) Journal of Molecular Structure. 891, 1-3, p. 491-497
Both closed and open framework structures were designed for copper complexes with N,N-bis-pyridin-2-ylmethyl-ethane-1,2-diamine (2-bpen)-based ligands. The design included substitution at the bridging aliphatic nitrogen atoms by reaction with cyanuric chloride to yield the 3,5-dichloro-2,4,6-triazine derivative. The chloride atoms on the triziane rings were further substituted by either electron donating amines, or an electron withdrawing thiomethyl moiety. The substitution of bridging nitrogen atoms by more electron donating aminated 2,4,6-triazines led to the formation of copper(II) complexes with closed square pyramidal architecture. On the other hand, substitution of bridging nitrogen atoms by the more electron withdrawing 2,4,6-triazines with thioether groups led to the formation of square planar or tetrahedral copper complexes with an open framework architecture whose specific structure and oxidation state depended on the anion.
Feller M., Iron M. A., Shimon L. J. W., Diskin Posner Y., Leitus G. & Milstein D. (2008) Journal of the American Chemical Society. 130, 44, p. 14374-14375
The Rh<sup>III</sup> complex [(PNP)Rh(CN)(CH<sub>3</sub>)][I] 5, obtained by oxidative addition of methyl iodide to [(PNP)Rh(CN)] 2, reacts selectively in two pathways: In aprotic solvents C-I reductive elimination of methyl iodide followed by its electrophilic attack on the cyano ligand takes place, giving the methyl isonitrile RhI complex [(PNP)Rh(CNCH<sub>3</sub>)][I] 3, while in protic solvents C-C reductive elimination of acetonitrile takes place forming an iodo RhI complex [(PNP)RhI] 9. Reaction of 2 with ethyl iodide in aprotic solvents gave the corresponding isonitrile complex, while in protic solvents no reactivity was observed. The selectivity of this reaction is likely due to a hydrogen bond between the cyano ligand and the protic solvent, as observed by X-ray diffraction, which retards electrophilic attack on this ligand.
Schaub T., Diskin Posner Y., Radius U. & Milstein D. (2008) Inorganic Chemistry. 47, 14, p. 6502-6512
The chloro-bridged rhodium and iridium complexes [M<sub>2</sub>(BTSE) <sub>2</sub>Cl<sub>2</sub>] (M = Rh 1, Ir 2) bearing the chelating bis-sulfoxide tBUSOC<sub>2</sub>H<sub>4</sub>SOtBU (BTSE) were prepared by the reaction of [M<sub>2</sub>(COE)<sub>4</sub>Cl<sub>2</sub>] (M = Rh, Ir; COE = cyclooctene) with an excess of a racemic mixture of the ligand. The cationic compounds [M(BTSE)<sub>2</sub>][PF<sub>6</sub>] (M = Rh 3, Ir 4), bearing one S- and one O-bonded sulfoxide, were also obtained in good yields. The chloro-bridges in 2 can be cleaved with 2-methyl-6-pyridinemethanol and 2-aminomethyl pyridine, resulting in the iridium(I) complexes [Ir(BTSE)(Py)(Cl)] (Py = 2-methyl-6-pyridinemethanol 5,2-aminomethyl-pyridine 6). In case of the bulky 2-hydroxy-isopropyl-pyridine, selective OH oxidative addition took place, forming the Ir(III)-hydride [Ir(BTSE)(2-isopropoxy-pyridine)(H)(Cl)] 7, with no competition from the six properly oriented C-H bonds. The cationic rhodium(I) and iridium(I) compounds [M(BTSE)(2-aminomethyl-pyridine)][X] (M = Rh 8, Ir 10), [Rh(BTSE)(2-hydroxy-isopropyl-pyridine)][X] 9(stabilized by intramolecular hydrogen bonding), [Ir(BTSE)(pyridine)<sub>2</sub>][PF<sub>6</sub>] 12, [Ir(BTSE)(α-picoline)<sub>2</sub>][PF<sub>6</sub>] 13, and [Rh(BTSE)(1,10-phenanthroline)][PF<sub>6</sub>] 14 were prepared either by chloride abstraction from the dimeric precursors or by replacement of the labile oxygen bonded sulfoxide in 3 or 4. Complex 14 exhibits a dimeric structure in the solid state by π-π stacking of the phenanthroline ligands.
Shirman T., Freeman D., Diskin Posner Y., Feldman I., Facchetti A. & van der Boom M. E. (2008) Journal of the American Chemical Society. 130, 26, p. 8162-8163
Polycrystalline halogen-bonded assemblies fabricated by physical vapor deposition (PVD) exhibit controllable morphologies and microstructures. Although the solid-state packing may vary going from a solution crystal growth process (used for chromophore single-crystal determination) to a vapor-phase deposition process (used for PVD film fabrication), the corresponding film microstructures are independent of the substrate surface chemistry.
Zenkina O., Altman M., Leitus G., Shimon L. J. W., Cohen R. & van der Boom M. E. (2007) Organometallics. 26, 18, p. 4528-4534
This contribution describes the reactivity of Pt(PEt<sub>3</sub>) <sub>4</sub> with (4-bromo-phenyl)-pyridin-4-yl-diazene. η<sup>2</sup>- Coordination of Pt(PEt<sub>3</sub>)<sub>2</sub> to the N=N moiety is kinetically preferable and followed by an aryl-halide bond activation process. This quantitative transformation proceeds under mild reaction conditions in solution and in the solid state. Mechanistic studies in solution indicate that the metal insertion into the aryl-halide bond is the rate-determining step. The reaction obeys first-order kinetics in the η<sup>2</sup>-coordination complex with ΔG<sup></sup><sub>298K</sub> = 24.6 ± 1.6 kcal/mol, ΔH<sup></sup> = 26.5 ± 1.6 kcal/mol, and ΔS <sup></sup> = 6.6 ± 5.0 eu. No effect on the reaction progress and NMR line shape has been observed in the presence of excess PEt<sub>3</sub>. However, competition experiments with the η-coordination complex and PhBr reveal that the product ratio can be altered by the presence of PEt<sub>3</sub>, indicating that the two aryl-halide bond activation processes proceed via different mechanistic pathways. Numerical analysis of a series of competition experiments fits a reaction scheme involving a unimolecular transformation from the η<sup>2</sup>-coordination complex to the product of aryl-halide oxidative addition. This "ring-walking" process is kinetically accessible as shown by density functional theory (DFT) calculations at the PCM:PBEO/SDB-cc-pVDZ/PBE0/SDD level of theory.
Weissman H., Shirman E., Ben Moshe T., Cohen R., Leitus G., Shimon L. J. W. & Rybtchinski B. (2007) Inorganic Chemistry. 46, 12, p. 4790-4792
We prepared the first σ-bonded metal complexes of widely utilized organic dyes, perylene tetracarboxylic acid diimides (PDIs). These 1,7-dipalladium PDI complexes were synthesized by C-Br oxidative addition of 1,7-dibromo-N,N-dicyclohexyl PDI (Br<sub>2</sub>PDI) to Pd(0) phosphine complexes bearing triphenylphosphine and bischelating 1,2-bis(diphenylphosphino) ethane (dppe). The structures of Pd-PDI complexes were elucidated by single-crystal X-ray analysis. Surprisingly, despite direct attachement of two late transition metal centers, Pd-PDI systems are highly fluorescent (Φ = 0.65 and 0.22 for triphenylphosphine and dppe systems, respectively). This is rationalized in terms of weak electronic interactions between the metal centers and PDI π-system, as revealed by TD-DFT calculations.
Zhang J., Gandelman M., Shimon L. J. W. & Milstein D. (2007) Dalton Transactions. 2007, 1, p. 107-113
Reaction of the electron-rich, bulky tridentate PNN ligand (PNN = 2-di-tert-butylphosphinomethyl-6-diethylaminomethylpyridine) with Ru(PPh <sub>3</sub>)<sub>3</sub>Cl<sub>2</sub> at 65 °C resulted in formation of the mononuclear dinitrogen complex (PNN)Ru(Cl)<sub>2</sub>N<sub>2</sub> 1a (minor) and the N<sub>2</sub> bridged Ru(ii) dinuclear complex [(PNN)Ru(Cl) <sub>2</sub>]<sub>2</sub>(-N<sub>2</sub>) 1b (major). These complexes can be interconverted; passing argon through a solution of the mixture resulted in formation of pure 1b. The cationic square-pyramidal [(PNN)Ru(PPh <sub>3</sub>)Cl]OTf 2 was obtained by the reaction of complex 1b with silver triflate followed by PPh<sub>3</sub>. Reaction of complex 1b with CO yielded (PNN)Ru(CO)Cl<sub>2</sub> 3, which upon reaction with one equiv. of AgBF <sub>4</sub> gave the cationic [(PNN)Ru(CO)Cl]BF<sub>4</sub> 4. The dicationic [(PNN)Ru(CO)(H<sub>2</sub>O)(acetone)](BF<sub>4</sub>)<sub>2</sub> 5 was obtained from 3 with 2 equiv. of AgBF<sub>4</sub> in acetone solution. Complexes 1b, 2 and 5 were structurally characterized by X-ray crystallography. Complexes 1b and 3, upon addition of an equivalent of base, catalyzed the dehydrogenation of secondary alcohols to the corresponding ketones and primary alcohols to esters in good yields and high selectivity accompanied with the evolution of hydrogen gas.
Vuzman D., Poverenov E., Diskin Posner Y., Leitus G., Shimon L. J. W. & Milstein D. (2007) Dalton Transactions. 2007, 48, p. 5692-5700
The synthesis and characterization of several Pt(ii) complexes, including formyl complexes, based on the PCP-type pincer ligands C<sub>6</sub>H <sub>4</sub>[CH<sub>2</sub>P(iPr)<sub>2</sub>]<sub>2</sub> (<sup>iPr</sup>PCP) and C<sub>6</sub>H<sub>4</sub>[CH<sub>2</sub>P(tBu)<sub>2</sub>]<sub>2</sub> (<sup>tBu</sup>PCP) are described. The chloride complex (<sup>iPr</sup>PCP)PtCl (6) and the unsaturated cationic complexes [(PCP)Pt]<sup>+</sup>X<sup>-</sup> (X = OTf<sup>-</sup>, BF<sub>4</sub><sup>-</sup>) (1, 7), based on both PCP ligands, were prepared and the latter reacted with carbon monoxide to give the corresponding cationic carbonyl complexes [(PCP)Pt(CO)]<sup>+</sup>X<sup>-</sup> (X = OTf<sup>-</sup>, BF<sub>4</sub><sup>-</sup>) (2, 8a). Hydride nucleophilic attack on both carbonyl complexes resulted in rare neutral platinum formyl complexes (<sup>iPr</sup>PCP)Pt(CHO) (3) and (<sup>tBu</sup>PCP)Pt(CHO) (9). Complex 3 undergoes decarbonylation to the corresponding hydride complex within hours at room temperature, while the bulkier complex 9 is more stable and undergoes complete decarbonylation only after 3-4 d. This observation demonstrates the very significant steric effect of the ligand on stabilization of the corresponding formyl complexes. Reaction of complex 9 with triflic acid resulted in the carbonyl complex [(<sup>tBu</sup>PCP)Pt(CO)]<sup>+</sup> OTf<sup>-</sup> (8b) with liberation of H<sub>2</sub>, an unusual transformation for a metal formyl. Reaction with methyl triflate resulted in the Fischer carbene-type complex, the methoxy-methylidene [(<sup>tBu</sup>PCP)Pt(CHOCH <sub>3</sub>)]<sup>+</sup>OTf<sup>-</sup> (11). The X-ray structures of complexes 2, 6, 8a and 11 were determined.
Montag M., Leitus G., Shimon L. L. W., Ben-David Y. & Milstein D. (2007) Chemistry - A European Journal. 13, 32, p. 9043-9055
Reaction of the aryl-monophosphine ligand α<sup>2</sup>- (diisopropylphosphino)isodurene (1) with the Rh<sup>I</sup> precursor [Rh(coe)<sub>2</sub>(acetone)<sub>2</sub>]BF<sub>4</sub> (coe = cyclooctene) in different solvents yielded complexes of all three common oxidation states of rhodium, depending on the solvent used. When the reaction was carried out in methanol a cyclometalated, solvent-stabilized Rh<sup>III</sup>alkylhydride complex (2) was obtained. However, when the reaction was carried out in acetone or dichloromethane a dinuclear η<sup>6</sup>-arene Rh<sup>II</sup> complex (5) was obtained in the absence of addedredox reagents. Moreover, when acetonitrile was added to a solution of either the Rh<sup>II</sup> or Rh <sup>III</sup> complexes, a new solvent-stabilized, noncyclometalated Rh <sup>I</sup> complex (6) was obtained. In this report we describe the different complexes, which were fully characterized, and probe the processes behind the remarkable solvent effect observed.
Jindou S., Petkun S., Shimon L., Bayer E., Lamed R. & Frolow F. (2007) Acta Crystallographica Section F-Structural Biology And Crystallization Communications. 63, 12, p. 1044-1047
Family 3 carbohydrate-binding modules (CBM3s) are associated with the scaffoldin subunit of the multi-enzyme cellulosome complex and with the family 9 glycoside hydrolases, which are multimodular enzymes that act on plant cell-wall polysaccharides, notably cellulose. Here, the crystallization of CBM3b from cellobiohydrolase 9A is reported. The crystals are tetragonal and belong to space group P41 or P43. X-ray diffraction data for CBM3b have been collected to 2.68 Å resolution on beamline ID14-4 at the ESRF.
Lucassen A. C. B., Zubkov T., Shimon L. J. W. & van der Boom M. E. (2007) CrystEngComm. 9, 7, p. 538-540
A new partially fluorinated stilbazole represents the first example of a halogen bonding based donor-acceptor system which exhibits an intriguing solid-state structure consisting of infinite parallel helices.
Gauvin R. M., Rozenberg H., Shimon L. J. W., Ben-David Y. & Milstein D. (2007) Chemistry - A European Journal. 13, 5, p. 1382-1393
The diphosphine 2,4,6-(CH<sub>3</sub>)<sub>3</sub>-3,5-(iPr <sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>OH (1) reacts with [OsCl<sub>2</sub>(PPh<sub>3</sub>)<sub>3</sub>] in presence of an excess of triethylamine to yield the isomeric para-quinone methide derivatives [Os{4-(CH<sub>2</sub>)-1-(O)-2,6-(CH<sub>3</sub>)<sub>2</sub>-3,5-(iPr <sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>}(Cl)(H)(PPh<sub>3</sub>)] (2 and 3), which differ in the positions of the mutually trans hydride and chloride ligands. Complex 2 reacts with CO to afford the dicarbonyl species [Os{1-(O)-2,4,6-(CH<sub>3</sub>)<sub>3</sub>-3,5-(iPr<sub>2</sub>PCH <sub>2</sub>)<sub>2</sub>C<sub>6</sub>}(Cl)(CO)<sub>2</sub>] (4), which results from hydride insertion into the quinonic double bond. Protonation of 2 and 3 leads to the formation of the methylene arenium derivative [Os{4-(CH <sub>2</sub>)-1-(OH)-2,6-(CH<sub>3</sub>)<sub>2</sub>-3,5-(iPr <sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>}(Cl)(H)(PPh <sub>3</sub>)]-[OSO<sub>2</sub>CF<sub>3</sub>] (5a). The diphosphine 1 reacts with [OsCl<sub>2</sub>(PPh<sub>3</sub>)<sub>3</sub>] at 100°C under H <sub>2</sub> to afford [Os{1-(OH)-2,6-(CH<sub>3</sub>)<sub>2</sub>-3,5-(iPr <sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>}(Cl)(H<sub>2</sub>)- (PPh<sub>3</sub>)] (6), a PCP pincer complex resulting formally from C(sp <sup>2</sup>) - C(sp<sup>3</sup>) cleavage of the C-CH<sub>3</sub> group in 1. C-C hydrogenolysis resulting in the same complex is achieved by heating 2 under H<sub>2</sub> pressure. Reaction of the diphosphine substrate with [OsCl <sub>2</sub>(PPh<sub>3</sub>)<sub>3</sub>] under H<sub>2</sub> at lower temperature allows the observation of a methylene arenium derivative resulting from C-H activation, [Os{4-(CH<sub>2</sub>)-1-(OH)-2,6-(CH<sub>3</sub>) <sub>2</sub>-3,5-(iPr<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C <sub>6</sub>}(Cl)<sub>2</sub>(H)] (7). This compound reacts with PPh<sub>3</sub> in toluene to afford the ionic derivative [Os(4-(CH<sub>2</sub>)-1-(OH)-2,6- (CH<sub>3</sub>)2-3,5-(iPr<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C <sub>6</sub>)(Cl)(H)(PPh<sub>3</sub>)]Cl (5b). X-ray diffraction studies have been carried out on compounds 2, 3, 4, 5b, 6, and 7, which allows the study of the structural variations when going from methylene arenium to quinone methide derivatives.
Shimon L. J., Rabinkov A., Shin I., Miron T., Mirelman D., Wilchek M. & Frolow F. (2007) Journal of Molecular Biology. 366, 2, p. 611-625
Alliinase (alliin lyase EC 4.4.1.4), a PLP-dependent α, β-eliminating lyase, constitutes one of the major protein components of garlic (Alliium sativum L.) bulbs. The enzyme is a homodimeric glycoprotein and catalyzes the conversion of a specific non-protein sulfur-containing amino acid alliin ((+S)-allyl-L-cysteine sulfoxide) to allicin (diallyl thiosulfinate, the well known biologically active component of freshly crushed garlic), pyruvate and ammonia. The enzyme was crystallized in the presence of (+S)-allyl-L-cysteine, forming dendrite-like monoclinic crystals. In addition, intentionally produced apo-enzyme was crystallized in tetragonal form. These structures of alliinase with associated glycans were resolved to 1.4 Å and 1.61 Å by molecular replacement. Branched hexasaccharide chains N-linked to Asn146 and trisaccharide chains N-linked to Asn328 are seen. The structure of hexasaccharide was found similar to "short chain complex vacuole type" oligosaccharide most commonly seen in plant glycoproteins. An unexpected state of the enzyme active site has been observed in the present structure. The electron density in the region of the cofactor made it possible to identify the cofactor moiety as aminoacrylate intermediate covalently bound to the PLP cofactor. It was found in the present structure to be stabilized by large number of interactions with surrounding protein residues. Moreover, the existence of the expected internal aldimine bond between the ε-amino group of Lys251 and the aldehyde of the PLP is ruled out on the basis of a distinct separation of electron density of Lys251. The structure of the active site cavity in the apo-form is nearly identical to that seen in the holo-form, with two sulfate ions, an acetate and several water molecules from crystallization conditions that replace and mimic the PLP cofactor.
Lucassen A. C. B., Karton A., Leitus G., Shimon L. J. W., Martin J. M. L. & van der Boom M. E. (2007) Crystal Growth & Design. 7, 2, p. 386-392
The potential triple-halogen-bond acceptor, sym-triiodo-trifluorobenzene IFB (1), has been co-crystallized with a series of bipyridyl derivatives (2-4) to gain insight to the factors controlling formation of multiple halogen bonds with a single aromatic system. Co-crystals 5-7 were obtained that consistently contained two N⋯I halogen bonds. The reluctance to the formation of a supramolecular assembly having a third N⋯I halogen bond does not depend on the size of the bispyridine donor systems (2-4). Apparently, there are limitations to the number of halogen bonds that can be formed with a single aromatic halogen donor. The solid-state structure of co-crystal (5) contains short I⋯F contacts of 2.96 and 3.05 A. DFT calculations were performed at the PBE0/(apc1-aSDBDZ)//PBEO/(pc1-SDBDZ) level of theory to investigate the nature of the interaction between the pyridine nitrogen and IFB (1). These calculations reveal a weakening of N⋯I interactions as more pyridine moieties coordinate to the IFB (1), which might be a contributing factor to the consistent formation of two rather than three N⋯I halogen bonds.
Rajasingh P., Cohen R., Shirman E., Shimon L. J. & Rybtchinski B. (2007) Journal of Organic Chemistry. 72, 16, p. 5973-5979
(Chemical Equation Presented) A novel method for the bromination of perylene diimides, PDI (1), under mild conditions is reported. Variation of the reaction conditions allows mono- and dibromination of PDIs to afford 2 and 3 (these can be separated through standard procedures) or exclusive dibromination to afford 3. Pure 1,7 regioisomers are obtained through repetitive crystallization. The structure of 1,7-3b was elucidated by a single-crystal X-ray analysis. The facility of the bromination reaction, which decreases in the order 1a > 1b > 1c, depends on PDI aggregation propensities. Monobrominated PDIs were utilized for the syntheses of novel unsymmetrical piperidinyl (4a and 4b) and trimethylsilylethynyl derivatives (5a and 5b). Computational studies (DFT) on imide substituent rotation in PDIs reveal that in the case of bulky groups there is a restricted rotation leading to isomers, in agreement with our experimental results. An aromatic core twist in PDIs bearing one and two bromine substituents was also investigated by DFT.
Poverenov E., Shimon L. J. W. & Milstein D. (2007) Organometallics. 26, 9, p. 2178-2182
Quinone methides (QMs) are highly reactive compounds that play important roles in various chemical and biological processes. In this work, a stable imino-pyridine platinum(IV) complex that bears a silylprotected oxy-benzyl precursor of the quinone methide BHT - QM, derived from the food preservative 2,6-di-tert-butyl-4-metnylphenol (BHT), was prepared and fully characterized, including by X-ray structural characterization. De-silylation results in a rarely observed, fully characterized, zwitterionic intermediate η<sup>1</sup>-methylene-p-phenoxy-Pt(IV), which undergoes de-aromatization to the unstable BHT - QM, which was trapped in solution.
Schwartsburd L., Poverenov E., Shimon L. J. W. & Milstein D. (2007) Organometallics. 26, 11, p. 2931-2936
A series of naphthyl-based PCP Pt(II) complexes was synthesized and characterized. A single-crystal X-ray study of (PCP)PtCl (2) reveals stacking of the aromatic units between each pair of molecules of 2. Chloride abstraction from 2 under nitrogen atmosphere leads to formation of the unsaturated cationic complex [(PCP)Pt]<sup>+</sup>BF<sub>4</sub><sup>-</sup> (3), with the metal center being stabilized by the counteranion (3a) or by the solvent (3b). Abstraction of the chloride ligand from 2 under CO atmosphere leads to formation of the cationic carbonyl complex [(PCP)Pt(CO)]<sup>+</sup>BF<sub>4</sub> <sup>-</sup> (4), containing an electrophilic carbonyl ligand. The latter is attacked by nucleophiles (MeO<sup>-</sup> and H<sup>-</sup>) to give the platinum carbomethoxy complex 5 and a rare platinum formyl complex, 6. Stabilized by the bulky bis-chelating tridentate pincer-type system, the formyl complex 6 was isolated and characterized. Complex 6 is more stable than the previously reported platinum formyls. At room temperature complex 6 is slowly converted (during days) into a hydride complex, 7.
Patra A., Wijsboom Y. H., Shimon L. J. W. & Bendikov M. (2007) ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 46, 46, p. 8814-8818
(Figure Presented) Planar, but non-aromatic: The title [6]radialenes, which contain thiophene and selenophene units (see the ORTEP diagrams), can be prepared in a straightforward manner. X-ray crystal structures and the results of theoretical studies show that the central six-membered ring of these compounds, although planar and composed entirely of sp <sup>2</sup>-hybridized carbon atoms, is completely non-aromatic.
Frech C. M., Shimon L. J. W. & Milstein D. (2007) Chemistry - A European Journal. 13, 26, p. 7501-7509
The PCP-Rh<sup>1</sup> complex la based on the [1,3-phenylenebis(methylene) ]bis(diisopropylphosphine) ligand reacts with [diazo-(phenyl)methyl] trimethylstannane (2) at room temperature to give novel pincer-type phenyl(dimethylstannyl)-methylene]hydrazinato complex 3a. The reaction sequence involves a unique combination of Sn-C bond cleavage, C-C bond formation, C-H activation and intramolecular deprotonation of a rhodium hydride intermediate, which results in methylene transfer from an SnMe group to the pincer system and PCP-chelate expansion. A methylene-transfer reaction was also demonstrated with tetramethyltin as the methylene source in the presence of KOC(CH <sub>3</sub>)<sub>3</sub> at room temperature. The resulting unstable "chelate-expanded" Rh<sup>1</sup> complex [(C<sub>10</sub>H <sub>5</sub>-(CH<sub>2</sub>P/Pr<sub>2</sub>)<sub>2</sub>)(CH<sub>2</sub>)Rh(L)] (L = N<sub>2</sub>, THF; 4a) was isolated as its carbonyl derivative 5 a. Heating 4 a in benzene yielded an equimolar amount of toluene and la, which demonstrates the ability of the Rh<sup>1</sup> pincer complex to extract a methylene group from an unactivated alkyl tin substrate and transfer it, via C-C followed by C-H activation, to an arene. Use of fluorobenzene resulted in formation of fluorotoluene. Catalytic methylene-group transfer mediated by la was not possible, because of formation of o-xylylene complex 8 under the reaction conditions. Steric parameters play a decisive role in the reactivity with tin compounds; while iPrP derivative la underwent facile reactions, tBuP complex lb was inert.
Di Salvo S. F., Escola N., Scherlis D. A., Estrin D. A., Bondia C., Murgida D., Ramallo-Lopez J. M., Requejo F. G., Shimon L. & Doctorovich F. (2007) Chemistry-A European Journal. 13, 30, p. 8428-8436
The nitrosyl in [IrCl<sub>5</sub>(NO)]<sup>-</sup> is probably the most electrophilic known to date. This fact is reflected by its extremely high IR frequency in the solid state, electrochemical behavior, and remarkable reactivity in solution. PPh<sub>4</sub>[IrCl<sub>5</sub>(NO)] forms a crystal in which the [IrCl<sub>5</sub>(NO)]<sup>-</sup> anions are in a curious wire-like linear arrangement, in which the distance between the N - O moiety of one anion and the trans chloride of the upper one nearby is only 2.8 Å. For the same complex [IrCl<sub>5</sub>(NO)]<sup>-</sup> but with a different counterion, Na[IrCl<sub>5</sub>(NO)], the anions are stacked one over the other in a side-by-side arrangement. In this case the electronic distribution can be depicted as the closed-shell electronic structure Ir<sup>III</sup>-NO <sup>+</sup>, as expected for any d<sup>6</sup> third-row transition metal complex. However, in PPh<sub>4</sub>[IrCl<sub>5</sub>(NO)] an unprecedented electronic perturbation takes place, probably due to NȮ-Cl<sup>-</sup> acceptor-donor interactions among a large number of [IrCl<sub>5</sub>(NO)] <sup>-</sup> units, favoring a different electronic distribution, namely the open-shell electronic structure Ir<sup>IV</sup>-NȮ. This conclusion is based on XANES experimental evidence, which demonstrates that the formal oxidation state for iridium in PPh<sub>4</sub>-[IrCl<sub>5</sub>(NO)] is +4, as compared with + 3 in K[IrCl<sub>5</sub>(NO)], In agreement, solid-state DFT calculations show that the ground state for [IrCl<sub>5</sub>(NO)]<sup>-</sup> in the PPh<sub>4</sub><sup>+</sup> salt comprises an open-shell singlet with an electronic structure which encompasses half of the spin density mainly localized on a metal-centered orbital, and the other half on an NO-based orbital. The electronic perturbation could be seen as an electron promotion from a metal-chloride to a metal-NO orbital, due to the small HOMO-LUMO gap in PPh <sub>4</sub>-[IrCl<sub>5</sub>(NO)]. This is probably induced by electrostatic interactions acting as a result of the closeness and wire-like spatial arrangement of the Ir metal centers, imposed by lattice forces due to π-π stacking interactions among the phenyl rings in PPh<sub>4</sub><sup>+</sup>. Experimental and theoretical data indicate that in PPh<sub>4</sub>[IrCl <sub>5</sub>(NO)] the Ir - N - O moiety is partially bent and tilted.
Feller M., Ben-Ari E., Gupta T., Shimon L. J. W., Leitus G., Diskin Posner Y., Weiner L. & Milstein D. (2007) Inorganic Chemistry. 46, 25, p. 10479-10490
The Rh(II) mononuclear complexes [(PNP<sup>t</sup>Bu)RhCl][BF<sub>4</sub>] (2), [(PNP<sup>t</sup>Bu)Rh(OC(O)CF<sub>3</sub>)][OC(O)CF<sub>3</sub>] (4), and [(PNP<sup>t</sup>Bu)Rh(acetone)][BF<sub>4</sub>]<sub>2</sub> (6) were synthesized by oxidation of the corresponding Rh(I) analogs with silver salts. On the other hand, treatment of (PNP<sup>t</sup>Bu)RhCl with AgOC(O)CF <sub>3</sub> led only to chloride abstraction, with no oxidation. 2 and 6 were characterized by X-ray diffraction, EPR, cyclic voltammetry, and dipole moment measurements. 2 and 6 react with NO gas to give the diamagnetic complexes [(PNP<sup>t</sup>Bu)Rh(NO)Cl][BF<sub>4</sub>] (7) and [(PNP<sup>t</sup>Bu)Rh(NO) (acetone)]-[BF<sub>4</sub>]<sub>2</sub> (8) respectively. 6 is reduced to Rh(I) in the presence of phosphines, CO, or isonitriles to give the Rh(I) complexes [(PNP<sup>t</sup>Bu)Rh(PR<sub>3</sub>)][BF<sub>4</sub>] (11, 12) (R = Et, Ph), [(PNP<sup>t</sup>Bu)Rh(CO)][BF<sub>4</sub>] (13) and [(PNP<sup>t</sup>Bu)Rh(L)] [BF<sub>4</sub>] (15, 16) (L = tert-butyl isonitrile or 2,6-dimethylphenyl isonitrile), respectively. On the other hand, 2 disproportionates to Rh(I) and Rh(III) complexes in the presence of acetonitrile, isonitriles, or CO. 2 is also reduced by triethylphosphine and water to Rh(I) complexes [(PNP <sup>t</sup>Bu)RhCl] (1) and [(PNP<sup>t</sup>Bu)Rh(PEt<sub>3</sub>)][BF <sub>4</sub>] (11). When triphenylphosphine and water are used, the reduced Rh(I) complex reacts with a proton, which is formed in the redox reaction, to give a Rh(III) complex with a coordinated BF<sub>4</sub>, [(PNP <sup>t</sup>Bu)Rh(Cl)(H)(BF<sub>4</sub>)] (9).
Branytska O., Shimon L. J. & Neumann R. (2007) Chemical Communications. 38, p. 3957-3959
Together with a strongly oxidizing polyoxometalate, H<sub>5</sub>PV <sub>2</sub>Mo<sub>10</sub>O<sub>40</sub>, Pt<sup>II</sup>(N-(2,6- diisopropylphenyl)pyrazin-2-ylmethanimine)Cl<sub>2</sub> forms a combined catalyst that was active in the tandem pinacol coupling-rearrangement of aryl aldehydes to give mostly the corresponding diarylacetaldehyde in high yields using molecular hydrogen as the reducing agent.
Zhang J., Gandelman M., Herrman D., Leitus G., Shimon L., Ben David Y. & Milstein D. (2006) Inorganica Chimica Acta. 359, 6, p. 1955-1960
Reaction of the PNN ligand ((2-(di-tert-butylphosphinomethyl)-6- diethylaminomethyl)pyridine) with 1 equiv. of anhydrous FeCl<sub>2</sub> in THF results in the formation of (PNN)FeCl<sub>2</sub> (1). The cationic complex [(PNN)Fe(THF)Cl](PF<sub>6</sub>) (2) was obtained by chloride abstraction from 1 with 1 equiv. of TlPF<sub>6</sub>. Similarly, the PNP-type complexes 3 and 4 were obtained from FeCl<sub>2</sub> with 1 equiv. of t-Bu-PNP (2,6-bis(di-tert-butylphosphinomethyl)pyridine) and i-Pr-PNP (2,6-bis(di-iso-propylphosphinomethyl)pyridine), respectively. Complexes 1 and 3 were characterized by X-ray diffraction and elemental analyses. In both structures the Fe(II) centers exhibit a distorted square pyramidal geometry comprising two chloride ligands and one tridentate PNN or PNP ligand. The magnetic properties of the paramagnetic complexes 1-4 are discussed.
Frech C. M., Shimon L. J. W. & Milstein D. (2006) Helvetica Chimica Acta. 89, 8, p. 1730-1739
Treatment of [{Me<sub>2</sub>C<sub>6</sub>H(CH<sub>2</sub>P <sup>t</sup>Bu<sub>2</sub>)<sub>2</sub>}Rh(η<sup>1</sup>-N<sub>2</sub>)] (1a) with molecular oxygen (O<sub>2</sub>) resulted in almost quantitative formation of the dioxygen adduct [{Me<sub>2</sub>C<sub>6</sub>H(CH <sub>2</sub>P<sup>t</sup>Bu<sub>2</sub>)<sub>2</sub>}Rh(η<sup>2</sup>-O <sub>2</sub>)] (2a). An X-ray diffraction study of 2a revealed the shortest O-O bond reported for Rh-O<sub>2</sub> complexes, indicating the formation of a Rh<sup>I</sup>-O<sub>2</sub> adduct, rather than a cyclic Rh<sup>III</sup> η<sup>2</sup>-peroxo complex. The coordination of the O<sub>2</sub> ligand in 2a was shown to be reversible. Treatment of 2a with CO gas yielded almost quantitatively the corresponding carbonyl complex [{Me<sub>2</sub>C <sub>6</sub>H(CH<sub>2</sub>P<sup>t</sup>Bu<sub>2</sub>)<sub>2</sub>}Rh(CO)] (3a). Surprisingly, treatment of the structurally very similar pincer complex [{C<sub>6</sub>H<sub>3</sub>(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>) <sub>2</sub>)}Rh(η<sup>1</sup>-N2)] (1b) with O<sub>2</sub> led to partial decomposition, with no dioxygen adduct being observed.
Lucassen A. C. B., Shimon L. J. W. & van der Boom M. E. (2006) Organometallics. 25, 14, p. 3308-3310
Reaction of a zerovalent platinum complex with a partially fluorinated stilbazole ligand results in direct Ar<sub>f</sub>-Br oxidation addition. The exclusive formation of the Ar<sub>f</sub>-Pt<sup>II</sup>-Br complex does not proceed via η<sup>2</sup>-C=C coordination on the reaction coordinate or as a side-equilibrium prior to the observed C-Br bond activation. Ar<sub>f</sub>-Br activation by Pt<sup>0</sup> is the kinetically and most probably also the thermodynamically favorable process independent of the reaction temperature and solvent polarity. This is in stark contrast with the reactivity of isostructural nonfluorinated stilbazole systems, where there is a lower barrier for η<sup>2</sup>-C=C coordination than for Ar-Br oxidative addition with Pt<sup>0</sup>.
Khenkin A. M., Carl P., Baute D., Raitsimring A. M., Astashkin A. V., Shimon L. J. W., Goldfarb D. & Neumann R. (2006) Inorganica Chimica Acta. 359, 9, p. 3072-3078
An EPR spectrum of as synthesized [G.A. Tsigdinos, C.J. Hallada, Inorg. Chem. 7 (1968) 437-441], orange colored, H<sub>5</sub>PV<sub>2</sub>Mo<sub>10</sub>O<sub>40</sub> polyoxometalate showed the presence of a reduced vanadium(IV) addenda atom. Surprisingly, further <sup>31</sup>P ENDOR (electron-nuclear double resonance) measurements indicated the absence of a phosphorous heteroatom leading to the suggestion that H<sub>5</sub>V<sup>V</sup>V<sup>IV</sup>Mo<sub>11</sub>O<sub>40</sub> exists as a previously unrecognized impurity in the typically synthesized H<sub>5</sub>PV<sub>2</sub>Mo<sub>10</sub>O<sub>40</sub> compound. H<sub>5/4</sub>PV<sup>V</sup>O<sub>4</sub>V<sup>IV/V</sup>Mo<sub>11</sub>O<sub>36</sub> was then synthesized in low yield (0.8 mol%) by omitting the addition of phosphate in a typical H<sub>5</sub>PV<sub>2</sub>Mo<sub>10</sub>O<sub>40</sub> preparation. The molecular formulation and structure was supported by X-ray crystallography, infrared and mass spectrometry. Further use of EPR/ENDOR/ESEEM (electron-spin echo envelope modulation) allowed the formulation of [V<sup>V</sup>V<sup>IV</sup>Mo<sub>11</sub>O<sub>40</sub>]<sup>5-</sup> as [V<sup>V</sup>O<sub>4</sub>V<sup>IV</sup>Mo<sub>11</sub>O<sub>36</sub>]<sup>5-</sup>. Accordingly, the polyoxometalate has a multiscripts(VO, 4, mml:none(), mml:none(), 3 -) heteroatom core with 11 molybdenum addenda and one VO<sup>2+</sup> moiety at the polyoxometalate surface. The redox potential and the catalytic activity of the new vanadomolybdate polyoxometalate compound were essentially identical to the often-studied H<sub>5</sub>PV<sub>2</sub>Mo<sub>10</sub>O<sub>40</sub> polyoxometalate isomeric mixture.
Salem H., Ben David Y., Shimon L. J. W. & Milstein D. (2006) Organometallics. 25, 9, p. 2292-2300
Exclusive C-C bond activation involving the new bisphosphinite ligand {C<sub>6</sub>H<sub>3</sub>(CH<sub>3</sub>)[OP(<sup>i</sup>Pr)<sub>2</sub>] <sub>2</sub>} (1) was observed at room temperature, upon reaction with the cationic complex [Rh(COE)<sub>2</sub>(THF)<sub>2</sub>]BF<sub>4</sub> (COE = cyclooctene) in THF, yielding the Rh(III) complex [(POCOP)Rh(Me)]BF<sub>4</sub> (2) (POCOP = C<sub>6</sub>H<sub>3</sub>[OP(<sup>i</sup>Pr)<sub>2</sub>] <sub>2</sub>). No parallel C-H activation was observed. This preference is assumed to be governed by the better directed phosphinite-bound metal center toward the C-C bond. A single-crystal X-ray diffraction analysis of complex 2 revealed a square pyramidal geometry with the BF<sub>4</sub><sup>-</sup> ion coordinated to the metal center. Complex 2 reacted with H<sub>2</sub> at room temperature in THF to yield the Rh(III)-hydrido complex 3 and methane. Deprotonation of 3 with KO<sup>t</sup>Bu yielded the Rh(I) dinitrogen complex [(POCOP)Rh]<sub>2</sub>(μ-N<sub>2</sub>) (4), which upon reaction with 1 equiv of CO or ethylene formed (POCOP)Rh(CO) (5) or (POCOP)Rh-(C <sub>2</sub>H<sub>4</sub>) (6), respectively. Complex 4 readily underwent oxidative addition of Mel, benzyl chloride, and benzyl bromide, forming complexes 7, 8, and 9, respectively. Halide abstraction from complex 9 with AgBF<sub>4</sub> led to the cationic benzyl complex 12, bearing a coordinated BF<sub>4</sub><sup>-</sup> ion as observed by a single-crystal X-ray diffraction analysis. Finally, we report an apparent α-H elimination from Rh(III)-Me, which takes place upon heating of the C-C activation product 2 at 150°C in the solid state, yielding the hydride complex 3 and ethylene.
Shimon L., Goihberg E., Peretz M., Burstein Y. & Frolow F. (2006) Acta Crystallographica Section D: Biological Crystallography. 62, 5, p. 541-547
The structure of the apo form of alcohol dehydrogenase from a single-cell eukaryotic source, Entamoeba histolytica, has been determined at 1.8 Å. To date, bacterial and archeal alcohol dehydrogenases, which are biologically active as tetramers, have crystallized with tetramers in the asymmetric unit. However, the current structure has one independent dimer per asymmetric unit and the full tetramer is generated by application of the crystallographic twofold symmetry element. This structure reveals that many of the crystallization and cryoprotection components, such as cacodylate, ethylene glycol, zinc ions and acetate, have been incorporated. These crystallization solution elements are found within the molecule and at the packing interfaces as an integral part of the three-dimensional arrangements of the tetramers. In addition, an unexpected modification of aspartic acid to O-carboxysulfanyl-4-oxo-L-homoserine was found at residue 245.
Illos R. A., Shamir D., Shimon L. J. W., Zilbermann I. & Bittner S. (2006) Tetrahedron Letters. 47, 31, p. 5543-5546
A new 'push-pull' molecule having an efficient fluorophore (dansyl) in electronic communication with an active redox quencher (phenyl-carbazoloquinone) through an NH-bridge was designed and synthesized. This all-organic molecule is suggested as a highly reversible 'on/off' molecular switching system. Chemical and electrochemical inter-conversion between the quinone acceptor and the dansyl donor were demonstrated via UV-vis, cyclic voltammetry and fluorescence measurements.
Ben-Ari E., Leitus G., Shimon L. J. W. & Milstein D. (2006) Journal of the American Chemical Society. 128, 48, p. 15390-15391
Unusual reactions are reported, in which the aromatic PNP ligand (PNP = 2,6-bis-(di-tert-butylphosphinomethyl)pyridine) acts in concert with the metal in the activation of H2 and benzene, via facile aromatization/dearomatization processes of the ligand. A new, dearomatized electron-rich (PNP*)Ir(I) complex 2 (PNP* = deprotonated PNP) activates benzene to form the aromatic (PNP)Ir(I)Ph 4, which upon treatment with CO undergoes a surprising oxidation process to form (PNP*)Ir(III)(H)CO 6, involving proton migration from the ligand \u201carm\u201d to the metal, with concomitant dearomatization. 4 undergoes stereoselective activation of H2 to exclusively form the trans-dihydride 7, rather than the expected cis-dihydride complex. Our evidence, including D-labeling, suggests the possibility that the Ir(I)−Ph complex is transformed to the dearomatized Ir(III)(Ph)(H) (independently prepared at low temperature), which may be the actual intermediate undergoing H2 activation.
Ben-Ari E., Cohen R., Gandelman M., Shimon L. J. W., Martin J. M. L. & Milstein D. (2006) Organometallics. 25, 13, p. 3190-3210
Reaction of (PNP)Ir(COE)<sup>+</sup>PF<sub>6</sub><sup>-</sup> (1) (PNP = 2,6-bis(di-tert-butylphosphinomethyl)pyridine; COE = cyclooctene) with benzene yields a stable unsaturated square pyramidal Ir(III) hydrido-aryl complex, 2, which undergoes arene exchange upon reaction with other arenes at 50 °C. Upon reaction of 1 with haloarenes (chlorobenzene and bromobenzene) and anisole at 50 °C, selective ortho C - H activation takes place. No C - halogen bond activation was observed, even in the case of the normally reactive bromobenzene and despite the steric hindrance imposed by the halo substituent. The ortho-activated complexes (8a, 9a, and 10a) exhibited a higher barrier to arene exchange; that is, no exchange took place when heating at a temperature as high as 60 °C. These complexes were more stable, both thermodynamically and kinetically, than the corresponding meta- and para-isomers (8b,c, 9b,c, and 10b,c). The observed selectivity is a result of coordination of the heteroatom to the metal center, which kinetically directs the metal to the ortho C - H bond and stabilizes the resulting complex thermodynamically. Upon reaction of complex 1 with fluorobenzene under the same conditions, no such selectivity was observed, due to low coordination ability of the fluorine substituent. Competition experiments showed that the ortho-activated complexes 8a, 9a, and 10a have similar kinetic stability, while thermodynamically the chloro and methoxy complexes 8a and 10a are more stable than the bromo complex 9a. Computational studies, using the mPW1K exchange - correlation functional and a variety of basis sets for PNP-based systems, provide mechanistic insight. The rate-determining step for the overall C - H activation process of benzene is COE dissociation to form a reactive 14e complex. This is followed by formation of a η<sup>2</sup><sub>c-c</sub> intermediate, which is converted into an η<sup>2</sup><sub>C-H</sub> complex, both being important intermediates in the C - H activation process. In the case of chlorobenzene, bromobenzene, and anisole, η<sup>1</sup>-coordination via the heteroatom to the 14e species followed by formation of the ortho η<sup>2</sup><sub>C-H</sub> complex leads to selective activation. The unobserved C - halide activation process was shown computationally in the case of chlorobenzene to involve the same Cl-coordinated intermediate as in the C - H activation process, but it experiences a higher activation barrier. The ortho C - H activation product is also thermodynamically more stable than the C - Cl oxidative addition complex.
Goikhman R., Karakuz T., Shimon L. J. W., Leitus G. & Milstein D. (2005) Canadian Journal of Chemistry. 83, 6-7, p. 786-792
New platinasiloxanes were synthesized and their reactivity was studied. Oxidative addition of (HSiMe<sub>2</sub>)<sub>2</sub>O to Pt(PEt <sub>3</sub>)<sub>3</sub> led to dehydrogenation and quantitative formation of the four-membered platinacyclosiloxane [(PEt<sub>3</sub>)<sub>2</sub>Pt- ((SiMe<sub>2</sub>)<sub>2</sub>O)] which was characterized by X-ray diffraction. This complex was stable towards non-polar substrates and aerobic conditions, but reacted readily with electrophiles and Lewis acids. Reaction with MeI resulted in ring opening, while MeOTf gave an oxonium complex, with retention of the platinacycle structure. A complex resulting from BF<sub>3</sub> coordination to the ring oxygen atom was also obtained. An unprecedented open-chain diplatinasiloxane containing the Pt-Si-O-Si-O-Si-Pt fragment was formed by oxidative addition of H-SiMe<sub>2</sub>-O-SiMe<sub>2</sub>-O- SiMe<sub>2</sub>-H to Pt(PEt<sub>3</sub>)<sub>3</sub> and it was characterized by X-ray diffraction.
Noach I., Frolow F., Jakoby H., Rosenheck S., Shimon L., Lamed R. & Bayer E. (2005) Journal of Molecular Biology. 348, 1, p. 1-12
The incorporation of enzymes into the multi-enzyme cellulosome complex and its anchoring to the bacterial cell surface are dictated by a set of binding interactions between two complementary protein modules: the cohesin and the dockerin. In this work, the X-ray crystal structure of a type-II cohesin from scaffoldin A of Bacteroides cellulosolvens has been determined to a resolution of 1.6 Å using molecular replacement. The type-II B. cellulosolvens cohesin (Bc-cohesin-II) is the first detailed description of a crystal structure for a type-II cohesin, and its features were compared with the known type-I cohesins from Clostridium thermocellum and Clostridium cellulolyticum (Ct-cohesin-I and Cc-cohesin-I, respectively). The overall jelly-roll topology of the type-II Bc-cohesin is very similar to that observed for the type-I cohesins with three additional secondary structures: an α-helix and two "β-flaps" that disrupt the normal course of a β-strand. In addition, β-strand 5 is elevated by approximately 4 Å on the surface of the molecule, relative to the type-I Ct and Cc-cohesins. Like its type-I analogue, the hydrophobic/aromatic core of Bc-cohesin-II comprises an upper and lower core, but an additional aromatic patch and conserved tryptophan at the crown of the molecule serves to stabilize the α-helix of the type-II cohesin. Comparison of Bc-cohesin-II with the known type-I cohesin-dockerin heterodimer suggests that each of the additional secondary structural elements assumes a flanking position relative to the putative dockerin-binding surface. The raised ridge formed by β-strand 5 confers additional distinctive topographic features to the proposed binding interface that collectively distinguish between the type-II and type-I cohesins.
Jacob D., Kahlenberg V., Wurst K., Solovyov L., Felner I., Shimon L. J. W., Gottlieb H. & Gedanken A. (2005) European Journal of Inorganic Chemistry. 3, p. 522-528
The ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, (BMI <sup>+</sup>)(PF<sub>6</sub><sup>-</sup>), has been used as a solvent in the sonochemical reaction of 1-methylimidazole and [Fe(CO)<sub>5</sub>] at 40-50 °C under air. The reaction afforded [(1-methylimidazole)<sub>6</sub>Fe <sup>II</sup>] (PF<sub>6</sub>)<sub>2</sub>, the structure of which was determined at 293 K by single-crystal X-ray diffraction methods. The salt crystallizes in the trigonal space group P3 with unit-cell parameters of a = 11.4603(16) Å, c = 8.0172(11) Å, and Z = 1. The crystals showed twinning by merohedry, which was accounted for in the structure determination and refinement calculations. All the 1-methylimidazole ligands are equivalent, with a Fe-N bond length of 2.204(3) Å. Mössbauer spectroscopy confirmed the presence of Fe<sup>2+</sup>.
Poverenov E., Leitus G., Shimon L. J. W. & Milstein D. (2005) Organometallics. 24, 24, p. 5937-5944
A series of the first C-metalated diazoalkane complexes of Pt, based on pincer-type PCN and PCP ligands (PCP = C<sub>6</sub>)H<sub>3</sub>[CH <sub>2</sub>P(iPr)<sub>2</sub>]<sub>2</sub>) PCN = C<sub>2</sub>H <sub>3</sub>[CH<sub>2</sub>P(tBu)<sub>2</sub>](CH<sub>2</sub>) <sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>), with the general formula (PCX)Pt[C(N<sub>2</sub>)R] (2, X = N, R = Ph; 3, X = N, R = SiMe<sub>3</sub>; 5, X = P, R = Ph) were prepared via direct nucleophilic attack of RCN <sub>2</sub><sup>-</sup>Li<sup>+</sup> at the metal center. These remarkably stable complexes were characterized by <sup>1</sup>H, <sup>31</sup>P{ <sup>1</sup>H}, and <sup>13</sup>C NMR and IR spectroscopy. Complex 2 was also characterized by single-crystal X-ray crystallography. Reactions of the C-metalated diazoalkane Pt complexes with Cu(I) (reported to catalyze decomposition of diazoalkanes) were strongly influenced by the nature of the pincer ligand. Bimolecular coupling to generate diphenylacetylene and (PCP)Pt-OTf (6) was observed in the case of the rigid PCP-based complex 5, while the hemilabile PCN-based complex 2 was converted to an ylide-bridged dimeric structure, the formation of which was promoted by the decoordination of the ligand amine arm. In addition, formation of the stable metalsubstituted azine-type binuclear complex 10, generated by reaction of 2 with Rh <sub>2</sub>(OAc)<sub>4</sub>, is described.
Rivenzon-Segal D., Wolf S. G., Shimon L. J. W., Willison K. & Horovitz A. (2005) Nature Structural & Molecular Biology. 12, 3, p. 233-237
The eukaryotic cytoplasmic chaperonin containing TCP-1 (CCT) is a hetero-oligomeric complex that assists the folding of actins, tubulins and other proteins in an ATP-dependent manner. To understand the allosteric transitions that occur during the functional cycle of CCT, we imaged the chaperonin complex in the presence of different ATP concentrations. Labeling by monoclonal antibodies that bind specifically to the CCTα and CCTδ subunits enabled alignment of all the CCT subunits of a given type in different particles. The analysis shows that the apo state of CCT has considerable apparent conformational heterogeneity that decreases with increasing ATP concentration. In contrast with the concerted allosteric switch of GroEL, ATP-induced conformational changes in CCT are found to spread around the ring in a sequential fashion that may facilitate domain-by-domain substrate folding. The approach described here can be used to unravel the allosteric mechanisms of other ring-shaped molecular machines.
Kossoy E., Iron M. A., Rybtchinski B., Ben-David Y., Shimon L. J. W., Konstantinovski L., Martin J. M. L. & Milstein D. (2005) Chemistry - A European Journal. 11, 8, p. 2319-2326
The novel pi-accepting, pincer-type ligand, dipyrrolylphoshinoxylene (DPyPX), is introduced. This ligand has the strongest pi-accepting phosphines used so far in the PCP family of ligands and this results in some unusual coordination chemistry. The rhodium(i) complex, [(DPyPX)Rh(CO)(PR3)] (4, R=Ph, Et, pyrrolyl) is prepared by treating the relevant [(DPyPX)Rh(PR3)] (3) complex with CO and is remarkably resistant to loss of either ligand. X-ray crystallographic analysis of complex 4b (R = Et) reveals an unusual cisoid coordination of the PCP phosphine ligands. These observations are supported by density functional theory (DFT) calculations.
Frech C. M., Shimon L. J. W. & Milstein D. (2005) Angewandte Chemie - International Edition. 44, 11, p. 1709-1711
Unequal partners: Oneelectron reduction of a pincertype palladium complex 1 results in collapse of the pincer system and formation of a novel bimetallic diamagnetic complex containing a linearly coordinated 14 e Pd0 center and a nonplanar PdII unit (2). The reaction is reversed by oxidation with Ag+ or organic halides. The catalytic activity of 2 is investigated for the Heck reaction.
Poverenov E., Gandelman M., Shimon L. J. W., Rozenberg H., Ben-David Y. & Milstein D. (2005) Organometallics. 24, 6, p. 1082-1090
The reactivity of the "long arm" PCN-type pincer ligand C <sub>6</sub>H<sub>4</sub>[CH<sub>2</sub>P(tBu)<sub>2</sub>](CH<sub>2</sub>) <sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub> (1), which forms complexes bearing a six-member ed amine chelate and a five-membered phosphine chelate, was compared with that of the new "normal" PCN ligand C<sub>6</sub>H <sub>4</sub>[CH<sub>2</sub>P-(tBu)<sub>2</sub>](CH<sub>2</sub>)N(CH <sub>2</sub>CH<sub>3</sub>)<sub>2</sub> (2), which leads to formation of complexes bearing two five-membered chelates. The chloride complexes (PCN)PtCl (3, 4) and the unsaturated cationic complexes [(PCN)Pt]<sup>+</sup>X<sup>-</sup> (X = BF<sub>4</sub>, OTf) (5,6,7), based on both PCN ligands, were prepared and reacted with different reagents to give aqua, [(PCN-1)Pt(H<sub>2</sub>O)] <sup>+</sup>BF<sub>4</sub><sup>-</sup> (10); hydroxo, (PCN-1)Pt(OH) (11); carbonyl [(PCN)Pt(CO)]<sup>+</sup>BF<sub>4</sub><sup>-</sup> (8, 9); and hydride, (PCN-1)PtH (16) complexes. The structures of complexes 4, 6, 8, 10, 11, and 12 were determined by X-ray crystallography. When both carbonyl complexes were treated with hydrogen gas, the "long arm" PCN-1-based complex 8 led to formation of a trimeric cluster, [C<sub>6</sub>H<sub>6</sub>[CH <sub>2</sub>P(tBu)<sub>2</sub>]-(CH<sub>2</sub>)<sub>2</sub>N(CH <sub>3</sub>)<sub>2</sub>Pt(CO)]<sub>3</sub> (12), while the "normal" PCN-based complex 9 remained unchanged under the same conditions. This observation clearly demonstrates the very significant effect of the amine arm length (five- vs six-membered chelate) on the hemilability of the ligand and the reactivity of the corresponding complexes.
Strawser D., Karton A., Zenkina O. V., Iron M. A., Shimon L. J. W., Martin J. M. L. & van der Boom M. E. (2005) Journal of the American Chemical Society. 127, 26, p. 9322-9323
The reaction between tetrakis(triethylphosphine)platinum(0) and 4-[trans-2-(4-bromophenyl)vinyl]pyridine (1) is examined. Initially, the metal center coordinates to the bridging double bond of 1. Complexes 2 and 3 were fully characterized, and their X-ray crystallography structures are presented. Upon heating, either in solution or in the solid state, complex 2 undergoes C-Br oxidative addition to give complex 3. Kinetic studies revealed that this conversion is unimolecular and does not involve dissociation of the metal center from the double bond. Density functional studies show that a plausible mechanism involves the metal center "walking" around the pi-system from the bridging C=C double bond to the C-Br bond.
Doctorovich F., Di Salvo S. F., Escola N., Trapani C. & Shimon L. J. W. (2005) Organometallics. 24, 20, p. 4707-4709
In the present work we describe the formation of primary aromatic and aliphatic coordinated nitrosamines by reaction of the extremely reactive K[IrCl<sub>5-</sub> NO] with p-toluidine and 2,2,2-trifluoroethylamine, respectively. After the counteranion of the product was changed to tetraphenylphosphonium, crystal structures could be determined by X-ray diffraction. Complexes containing the highly unstable primary nitrosamines as ligands are generally scarce; moreover, to our knowledge this is the first example of isolated primary nitrosamines coordinated to a metal center through the NO moiety.
Zhang J., Gandelman M., Shimon L. J. W., Rozenberg H. & Milstein D. (2004) Organometallics. 23, 17, p. 4026-4033
Reaction of the electron-rich, bulky tridentate PNP ligand (2,6-bis-(di-tert-butylphosphinomethyl)pyridine) with Ru(PPh<sub>3</sub>) <sub>3</sub>Cl<sub>2</sub> at 65°C resulted in formation of a solution containing the dinitrogen monomeric Ru(II) complex la and the N <sub>2</sub>-bridged dinuclear Ru(II) complex 1b, which can be interconverted. Passing argon through the solution results in formation of pure 1b. The Ru(II) hydride dinitrogen complex 2 was obtained by the reaction of complex 1b with 2 equiv of NaBEt<sub>3</sub>H. Complex 1b reacted with 4 equiv of AgOCOCF <sub>3</sub> to yield [Ru(PNP)(CF<sub>3</sub>COO)<sub>2</sub>], 3. The Ru(II) carbonyl hydride complex 4 was obtained by the reaction of PNP and Ru <sub>2</sub>(OAc)<sub>4</sub> in methanol as a result of O-H activation and decarbonylation of methanol. Complexes 1b, 2, and 4 were structurally characterized by X-ray crystallography. Complexes 1b and 2 catalyze the dehydrogenation of secondary alcohols to the corresponding ketones with good yields and high selectivity accompanied with the evolution of dihydrogen in a homogeneous system without a need for a hydrogen acceptor. The presumed intermediate Ru dihydride complex is generated in situ by reaction 1b or 2 with a base (1 equiv for each Ru-Cl bond), and the reaction can proceed in the absence of excess base or acid.
Weissman H., Shimon L. J. W. & Milstein D. (2004) Organometallics. 23, 16, p. 3931-3940
The 14e<sup>-</sup> Pd(0)L<sub>2</sub> complex 2 was prepared by reduction of [Pd(2-methylallyl)Cl]<sub>2</sub> in the presence of the new, electron-rich, bulky methoxy benzyl phosphine (dmobp) ligand 1. Structural characterization of this complex indicates that the methoxy groups are not coordinated to the metal center. Complex 2 undergoes oxidative addition of iodo- and chlorobenzene at room temperature to yield the monophosphine complexes LPd(Ph)X (4, X = I; 5, X = Cl) in which the methoxy group is coordinated to the Pd(II) center in the solid state, as indicated by the X-ray structure of 4. In solution there is no evidence for methoxy coordination, indicating the availability of a Pd(II) 14e<sup>-</sup> complex. The Me-O bond in 4 is longer than the corresponding bond in 2, indicating that coordination of the methoxy group weakens the C-O bond. Reaction of complex 4 or 5 with the free ligand 1 results in nucleophilic attack and C-O cleavage, leading to the dimeric phenoxy-bridged complex 7, which was structurally characterized. Partial reduction of [Pd(2-methylallyl)Cl] <sub>2</sub> in the presence of the ligand 1 leads to the Pd(I) dimer 3, which can be converted to the Pd(0) complex 2 by addition of ligand 1 and a base. This complex, which bears only one phosphine for each Pd atom, is a suitable precursor to a presumed catalytically active 12e<sup>-</sup> Pd(0) catalyst, Complexes 2 and 3 catalyze the Suzuki-Miyaura cross-coupling of chlorobenzene with PhB(OH)<sub>2</sub> even at room temperature, albeit slowly, while the C-O cleaved phenoxy-bridged complex 7 is not catalytically active at 40°C, indicating that it is not an intermediate in the catalysis. The dmobp ligand 1 is more effective in Suzuki-Miyaura coupling than an analogous benzyl ligand lacking methoxy substituents.
van der Boom M. E., Iron M. A., Atasoylu O., Shimon L. J. W., Rozenberg H., Ben-David Y., Konstantinovski L., Martin J. M. L. & Milstein D. (2004) Inorganica Chimica Acta. 357, 6, p. 1854-1864
Halide abstraction from the 18 electron Ru(II) complex RuCl(CO)(2)[2,6-(CH2P'Bu-2)(2)C6H3] (2) with AgPF6 results in the exclusive formation of the cationic complex {Ru(CO)(2)[2,6-(CH2P'Bu)(2)C6H3]}+PF6-(3). The molecular structures of 2 and 3 were determined by complete single-crystal diffraction studies. X-ray crystallographic analysis of 3 reveals that the "open" coordination site is occupied by an agostic interaction between the metal center and an sp(3) C-H bond of a tert-butyl substituent. DFT gas phase calculations (B97-1/SDD) show the necessity of two sterically demanding tert-butyl substituents on one P donor atom for the agostic interaction to occur. The reaction of 3 with H-2 results in the quantitative conversion to {Ru(H)(CO)(2)[2,6-((CH2PBu2)-Bu-t)(2)C6H4]}+PF6- (4) where the aromatic C-ipso-H bond is eta(2)-coordinated to the metal center. Treatment of the agostic complex 4 with Et3N results in the formation of the neutral complex Ru(H)(CO)(2)[2,6-((CH2PBu2)-Bu-t)(2)C6H3] (5). The mechanistic details of 3 + H-2 --> 4 were investigated by DFT calculations at the B97-1/SDB-cc-pVDZ//B97-1/SDD level of theory.
van der Boom M. E., Liou S., Shimon L. J. W., Ben-David Y. & Milstein D. (2004) Inorganica Chimica Acta. 357, 13, p. 4015-4023
Reaction of NiI<sub>2</sub> with the PCP-ligand {1-Et-2,6-(CH <sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-C<sub>6</sub>H <sub>3</sub>} (1) results in selective activation of the strong sp <sup>2</sup>-sp<sup>3</sup> aryl-ethyl bond to afford the aryl-nickel complex [Ni{2,6-(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-C <sub>6</sub>H<sub>3</sub>}I] (2), whereas reaction of NiI<sub>2</sub> with {1,3,5-(CH<sub>3</sub>)<sub>3</sub>-2,6-(CH<sub>2</sub>P<sup>i</sup>Pr <sub>2</sub>)<sub>2</sub>-C<sub>6</sub>H} (4) leads to the formation of the benzylic complex [Ni{1-CH<sub>2</sub>-2,6-(CH<sub>2</sub>P<sup>i</sup>Pr <sub>2</sub>)<sub>2</sub>-3,5-(CH<sub>3</sub>)<sub>2</sub>-C<sub>6</sub>H}I] (5) by selective C-H bond activation. Thermolysis of 5 results in formation of [Ni{2,6-(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-3,5-(CH <sub>3</sub>)<sub>2</sub>-C<sub>6</sub>H}I] (6) by activation of the sp <sup>2</sup>-sp<sup>3</sup> C-C bond. The identity of the new 16-electron complexes 2 and 6 was confirmed by reaction of NiI<sub>2</sub> with {1,3-(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-C<sub>6</sub>H <sub>4</sub>} (3) and {1,3-(CH<sub>3</sub>)<sub>2</sub>-4,6-(CH <sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-C<sub>6</sub>H <sub>2</sub>} (7), respectively, lacking the aryl-alkyl groups between the "phosphines arms" (alkyl=ethyl, methyl). Complexes 2 and 5 have been fully characterized by X-ray analysis. Nickel-based activation of an unstrained C-O single bond was observed as well. Reaction of the aryl-methoxy bisphosphine {1-OMe-2,6-(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>2</sub>-C <sub>6</sub>H<sub>3</sub>} (8) with NiI<sub>2</sub> results in the formation of the phenoxy complex [Ni{1-O-2,6-(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>) <sub>2</sub>-C<sub>6</sub>H<sub>3</sub>}I] (9) by selective sp <sup>3</sup>-sp<sup>3</sup> C-O bond activation.
Vaganova E., Wachtel E., Rozenberg H., Khodorkovsky V., Leitus G., Shimon L. J. W., Reich S. & Yitzchaik S. (2004) Chemistry of Materials. 16, 21, p. 3976-3979
The cyclo-octasulfur (S<sub>8</sub>) molecule is presented as the basis for conductive Au/S<sub>8</sub> macrocrystalline systems. Photolysis of 4,4-dithiodipyridine in pyridine/water solution was used for the production of S<sub>8</sub> microcrystals. The mechanism of the photochemical reaction was verified by X-ray crystallography. The polymorphism of S <sub>8</sub> can be used for shape-controlled crystallization.
van der Boom M. E., Zubkov T., Shukla A. D., Rybtchinski B., Shimon L. J. W., Rozenberg H., Ben David Y. & Milstein D. (2004) Angewandte Chemie - International Edition. 43, 44, p. 5961-5963
Do-it-yourself oxidation: The Rh<sup>III</sup> complex 1 undergoes a self-oxidative coupling process, in which the phenolate oxygen atom serves as the oxidant, to give 2 and the hydride complex 3 (2:3 = 1:3). This reaction involves cleavage of a strong aryl-oxygen bond. X-ray analysis of 2 reveals that the two quinonoid C=O bonds are n<sup>2</sup>-coordinated to the metal centers.
Poverenov E., Gandelman M., Shimon L. J. W., Rozenberg H., Ben-David Y. & Milstein D. (2004) Chemistry - A European Journal. 10, 19, p. 4673-4684
Novel anionic dialkyl, diaryl, and dihydride platinum(II) complexes based on the new πlong-armπ hemilabile PCN-type ligand C<sub>6</sub>H <sub>4</sub>[CH<sub>2</sub>P(tBu)<sub>2</sub>](CH<sub>2</sub>) <sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub> with the general formula Li <sup>+</sup> [Pt(PCN)(R)<sub>2</sub>]<sup>-</sup> (R = Me (4), Ph (6) and H (9)) were prepared by reaction of [Pt(PCN)(R)] complexes (obtained from the corresponding chlorides) with an equivalent of RLi, as a result of the opening of the chelate ring. Alkylating agents based on other metals produce less stable products. These anionic d<sup>8</sup> complexes are thermally stable although they bear no stabilizing π acceptors. They were characterized by <sup>1</sup>H, <sup>31</sup>P{<sup>1</sup>H}, <sup>13</sup>C, and <sup>7</sup>Li NMR spectroscopy; complex 9 was also characterized by single crystal X-ray crystallography, showing that the Li <sup>+</sup> ion is coordinated to the nitrogen atom of the open amine arm and to the hydride ligand (trans to the P atom) of a neighboring molecule (H-Li = 2.15 Å), resulting in a dimeric structure. Complexes 4 and 9 exhibit high nucleophilic reactivity, upon which the pincer complex is regenerated. Reaction of 4 with water, methyl iodide, and iodobenzene resulted in the neutral complex [Pt(PCN)(CH<sub>3</sub>)] (3) and methane, ethane, or toluene, respectively. Labeling studies indicate that the reaction proceeds by direct electrophilic attack on the metal center, rather than attack on the alkyl ligand. The anionic dihydride complex 9 reacted with water and methyl iodide to yield [Pt(PCN)(H)] (8) and H<sub>2</sub> or methane, respectively.
Dorta R., Shimon L. J. W. & Milstein D. (2004) Journal of Organometallic Chemistry. 689, 4, p. 751-758
The neutral complexes [Rh(I)(NBD)((1S)-10-camphorsulfonate)] (2) and [Rh(I)((R)-N-acetylphenylalanate)] (4) reacted with bis-(diphenylphosphino)ethane (dppe) to form the cationic Rh(I)(NBD)(dppe) complexes, 5 and 6, respectively, accompanied by their corresponding chiral counteranions. Analogously, 4 reacted with 4,4-dimethylbipyridine to yield complex 7. Complexes 5 and 6 disproportionated in aprotic solvents to form the corresponding bis-diphosphine complexes 8 and 9, respectively. 8 was characterized by an X-ray crystal structure analysis. In order to form achiral Rh(I) complexes bearing chiral countercations new sulfonated monophosphines 13-16 with chiral ammonium cations were synthesized. Tris-triphenylphosphinosulfonic acid (H<sub>3</sub>TPPS, 11) was used to protonate chiral amines to yield chiral ammonium phosphines 14-16. Thallium-tris-triphenylphosphinosulfonate (Tl<sub>3</sub>TPPS, 12) underwent metathesis with a chiral quartenary ammonium iodide to yield the proton free chiral ammonium phosphine 13. Phosphines 15 and 16 reacted with [Rh(NBD)<sub>2</sub>]BF<sub>4</sub> to afford the highly charged chiral zwitterionic complexes [Rh(NBD) (TPPS)<sub>2</sub>][(R)-N, N-dimethyl-1-(naphtyl)ethylammonium] <sub>5</sub> (17) and [Rh(NBD)(TPPS)<sub>2</sub>][BF<sub>4</sub>] [(R)-N, N-dimethyl-phenethylammonium]<sub>6</sub> (18), respectively. Complexes 5, 6, and 18 were tested as precatalysts for the hydrogenation of de-hydro-N-acetylphenylalanine (19) and methyl-(Z)-(α) -acetoamidocinnamate (MAC, 20) under homogeneous and heterogeneous (silica-supported and self-supported) conditions. None of the reactions was enantioselective.
Dorta R., Dorta R., Shimon L. J. W. & Milstein D. (2004) Inorganic Chemistry. 43, 22, p. 7180-7186
The synthesis of new ligand systems based on the bipyridine unit for bi- and trimetallic complexes, including a rare example of a chiral bimetallic complex, is presented. Ligands BBPX (bis-bipyridine-xylene, 3) and TBPBX (trisbipyridine-bis-xylene, 4) were prepared in one step by reacting α,α-dibromo-o-xylene (2) with 2 equiv of the monolithiated derivative of 4,4-dimethyl-2,2-bipyridine. Dilithium (S)-binaphtholate (5) reacted with 2 equiv of 4-bromomethyl-4-methyl-2, 2-bipyridine (6), affording ligand (S)-BBPBINAP (bis-bipyridine- binaphtholate, 7). These ligands reacted cleanly with 1, 1.5, and 1 equiv of the rhodium dimer [Rh<sub>2</sub>Cl<sub>2</sub>(HD)<sub>2</sub>] (HD = 1,5-hexadiene), respectively. Chloride abstraction led to the isolation of the cationic complexes BBPX[Rh(HD)BF<sub>4</sub>]<sub>2</sub> (8), TBPBX[Rh(HD)BF<sub>4</sub>]<sub>3</sub> (10), and (S)-BBPBINAP[Rh(HD)BF <sub>4</sub>]<sub>2</sub> (12). When BBPX (3), TBPBX (4), and (S)-BBPBINAP (7) were added to 2, 3, and 2 equiv of [Rh(NBD)<sub>2</sub>]BF<sub>4</sub> or [Rh(NBD)(CH<sub>3</sub>CN)<sub>2</sub>]BF<sub>4</sub> (NBD = norbornadiene), respectively, clean formation of BBPX[Rh(NBD)BF<sub>4</sub>]<sub>2</sub> (9), TBPBX[Rh(NBD)BF<sub>4</sub>]<sub>3</sub> (11), and (S)-BBPBINAP[Rh(NBD)BF <sub>4</sub>]<sub>2</sub> (13) was observed. The neutral iridium complex (S)-BBPBINAP[IrCl(COD)]<sub>2</sub> (14) was obtained by reaction of (S)-BBPBINAP (7) with 1 equiv of [Ir<sub>2</sub>Cl<sub>2</sub>(COD)<sub>2</sub>] (COD = cyclooctadiene). The complexes were fully characterized including X-ray structural studies of 8, 9, and 13, and preliminary studies on their catalytic activity were performed.
Band A., Albu-Yaron A., Livneh T., Cohen H., Feldman Y. (., Shimon L. J. W., Popovitz-Biro R., Lyahovitskaya V. & Tenne R. (2004) Journal Of Physical Chemistry B. 108, 33, p. 12360-12367
Cesium oxides are materials of great interest to the photodetection industry because of their relatively low work function (∼1 eV). Used mainly as coating films for photoemissive devices, they provide high wavelength thresholds and high photocurrents. However, they are unstable, air-sensitive, and hygroscopic, rendering them short-lived and limiting their applications. Although the technology of these devices is highly developed, their characterization on the micro- and nanoscale suffers from their poor chemical stability and poor crystallinity. In the present study, cesium oxides were synthesized from the elements and were characterized using a combination of chemical and structural analysis techniques. Because the reaction products were extremely sensitive to humidity, sample analysis without atmospheric exposure was essential, and techniques were developed for the transfer of the samples to the measurements systems. Extensive data obtained from X-ray energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), selected-area electron diffraction (SAED), X-ray diffraction (XRD), and Raman microscopy were obtained. Raman spectra with bands at 103, 742, and 1134 cm<sup>-1</sup> strongly confirmed the presence of the oxide, peroxide, and Superoxide ions, respectively, as well as the absence of carbonate as an impurity. The A<sub>1g</sub> mode of Cs<sub>2</sub>O was detected as an anti-Stokes band at 103 cm<sup>-1</sup>. This study provides further insight into the reactivity of the various cesium oxides.
Vasylyev M., Popovitz-Biro R., Shimon L. & Neumann R. (2003) Journal of Molecular Structure. 656, 1-3, p. 27-35
Co-crystallization of a tri-ammonium cation with short and somewhat flexible 'arms', [N,N,N-tris[2-(dimethylamino)ethyl]-1,3,5-benzenetricarboxamide]<sup>3+</sup>, with a polyoxometalate trianion, PW<sub>12</sub>O<sub>40</sub><sup>3-</sup>, yielded an insoluble channeled or microporous structure. The polyoxometalate clusters are arranged in a layered and zig-zag fashion along the xy plane. Looking along the x-axis, channels of a dimension of ∼3.5 × ∼6.5 Å are observed. It was found that C-H⋯O bonds aided in determining the crystal packing by providing directionality to the anion-cation interaction. On the other hand the co-crystallization of a tetraammonium cation with an extended and rigid tetrahedral configuration, 1,3,5,7-tetrakis{4-[(E)-2(N-methylpyridinium-4-yl)vinyl]phenyl adamantane tetraiodide, with a polyoxometalate tetracation, SiW<sub>12</sub>O <sub>40</sub><sup>4-</sup>, yielded a lamellar structure with alternating layers with spacing of 16.6 Å of the inorganic-organic hybrid material.
Gandelman M., Shimon L. J. W. & Milstein D. (2003) Chemistry - A European Journal. 9, 18, p. 4295-4300
Based on the PCN ligand 2, a remarkable degree of control over C-C versus C-H bond activation and versus formation of an agostic C-C complex was demonstrated by choice of cationic [Rh(CO)<sub>n</sub>(C<sub>2</sub>H <sub>4</sub>)<sub>2-n</sub>] (n=0, 1, 2) precursors. Whereas reaction of 2 with [Rh(C<sub>2</sub>H<sub>4</sub>)<sub>2</sub>(solv)<sub>n</sub>]BF<sub>4</sub> results in exclusive C-C bond activation to yield product 5, reaction with the dicarbonyl precursor [Rh(CO)<sub>2</sub>(solv)<sub>n</sub>]BF<sub>4</sub> leads to formation of the C-H activated complex 9. The latter process is promoted by intramolecular deprotonation of the C-H bond by the hemilabile amine arm of the PCN ligand. The mixed monocarbonyl monoethylene Rh species [Rh(CO)(C <sub>2</sub>H<sub>4</sub>)]BF<sub>4</sub> reacts with the PCN ligand 2 to give an agostic complex 7. The C-C activated complex 5 is easily converted to the C-H activated one (9) by reaction with CO; the reaction proceeds by a unique sequence of 1,2-metal-to-carbon methyl shift, agostic interaction, and C-H activation processes. Similarly, the C-C agostic complex 7 is converted to the same C-H activated product 9 by treatment with CO.
Khenkin A., Shimon L. & Neumann R. (2003) Inorganic Chemistry. 42, 10, p. 3331-3339
A new heptamolybdate polyoxometalate structure containing ruthenium(II) or osmium(II) metal centers, [M(II)(DMSO)<sub>3</sub>Mo<sub>7</sub>O<sub>24</sub>]<sup>4-</sup> (M = Ru, Os), was synthesized by reaction between (NH<sub>4</sub>)<sub>6</sub>Mo<sub>7</sub>O<sub>24</sub> and cis-M(DMSO)<sub>4</sub>Cl<sub>2</sub>. X-ray structure analysis revealed the complexes to contain a ruthenium/osmium center in a trigonal antiprismatic coordination mode bound to three DMSO moieties via the sulfur atom of DMSO and three oxygen atoms of the new heptamolybdate species. The heptamolybdate consists of seven condensed edge-sharing MoO<sub>6</sub> octahedra with C<sub>2v</sub> symmetry. Three Mo atoms are in classic type II octahedra with a cis dioxo configuration. Two Mo atoms are also type-II-like, but one of the short Mo-O bonds is associated with bridging oxygen atoms rather than terminal oxygen atoms. Two molybdenum atoms are unique in that they are in a trigonally distorted octahedral configuration with three short Mo-O bonds and two intermediate-long M-O bonds and one long Mo-O bond. The [M(II)(DMSO)<sub>3</sub>Mo<sub>7</sub>O<sub>24</sub>]<sup>4-</sup> polyoxometalates were effective and in some cases highly selective catalysts for the aerobic oxidation of alcohols to ketones/aldehydes. The integrity of the polyoxometalate was apparently retained at high turnover numbers and throughout the reaction, and a variation of an oxometal type mechanism was proposed to explain the results.
Goikhman R., Aizenberg M., Shimon L. J. W. & Milstein D. (2003) Organometallics. 22, 20, p. 4020-4024
Methods of metallo-silanol synthesis have been developed. The Ir(I) complex (Et<sub>3</sub>P)<sub>2</sub>Ir(C<sub>2</sub>H<sub>4</sub>)Cl (1) oxidatively adds secondary silanols R<sub>2</sub>SiHOH (R = <sup>i</sup>Pr, <sup>t</sup>Bu) to yield the iridium-silanol complexes [(Et<sub>3</sub>P)<sub>2</sub>Ir(H)(Cl)(SiR<sub>2</sub>OH)] (R = <sup>i</sup>Pr, 2; R = <sup>t</sup>Bu, 3). The crystal structure of 2 exhibits a trigonal-bipyramidal geometry, and intermolecular Si-O-H- - -Cl hydrogen bonding is present. Deprotonation of 2 results in the highly thermodynamically stable metallo-silanolate [(Et<sub>3</sub>P)<sub>2</sub>Ir(H)(Cl) (Si<sup>i</sup>Pr<sub>2</sub>OLi)]<sub>2</sub> (4). Compound 4 has an almost planar core, consisting of two atoms each of iridium, silicon, chlorine, oxygen, and lithium. Upon treatment of (Et<sub>3</sub>P)<sub>3</sub>RhCl with HSi<sup>i</sup>Pr<sub>2</sub>OH, the first Rh-silanol complex, trans-[(Et<sub>3</sub>P)<sub>2</sub>Rh(H)(Cl)(<sup>i</sup>PrSi<sub>2</sub>OH)], is formed in an equilibrium with the starting complex (K<sub>eq</sub> = 4 × 10<sup>-3</sup>); hence, the reaction is dependent on the concentration of the silanol and Et<sub>3</sub>P, an excess of the latter shifting the equilibrium to the starting compounds. Reaction of the bis-phosphine complex [(Et<sub>3</sub>P)<sub>2</sub>RhCl]<sub>2</sub> with the silanol, which does not generate free phosphine, results in 96% conversion to the adduct. On the other hand, the chelating bis-phosphine complex [(bis-(diisopropylphosphino)propane)RhCl]<sub>2</sub> does not add the silanol even in the presence of a 10-fold excess of the silanol, indicating that the cis-phosphine configuration in the adduct is unfavorable. In contrast to the Et<sub>3</sub>P-containing Ir complex, and similarly to the Rh complex, (PPh<sub>3</sub>)<sub>3</sub>Ir(CO)H reacts with <sup>i</sup>Pr<sub>2</sub>SiHOH reversibly, leading to 60% conversion to the metallosilanol (PPh<sub>3</sub>)<sub>2</sub>Ir(CO)(H)<sub>2</sub>(Si<sup>i</sup>Pr<sub>2</sub>O H) (6). A stable PPh<sub>3</sub>-containing Ir-silanol was prepared by starting from (PPh<sub>3</sub>)<sub>2</sub>Ir(CO)(H)<sub>2</sub>(Si(SEt)<sub>3</sub>). Following reaction with Et<sub>3</sub>SiOSO<sub>2</sub>CF<sub>3</sub> to exchange one SEt substituent with OSO<sub>2</sub>CF<sub>3</sub>, reaction with NaOH generates the stable silanol complex (PPh<sub>3</sub>)<sub>2</sub>Ir(CO)(H)<sub>2</sub>(Si(SEt)<sub>2</sub>OH) (14).
Noach I., Lamed R., Xu Q., Rosenheck S., Shimon L., Bayer E. & Frolow F. (2003) Acta Crystallographica Section D: Structural Biology. 59, 9, p. 1670-1673
The N-terminal type II cohesin from the cellulosomal ScaB subunit of Acetivibrio cellulolyticus was crystallized in two different crystal systems: orthorhombic (space group P2<sub>1</sub>2<sub>1</sub>2<sub>1</sub>), with unit-cell parameters a = 37.455, b = 55.780, c = 87.912 Å, and trigonal (space group P3<sub>1</sub>21), with unit-cell parameters a = 55.088, b = 55.088, c = 112.553 Å. The two crystals diffracted to 1.2 and 1.9 Å, respectively. A selenomethionine derivative was also crystallized and exhibited trigonal symmetry (space group P3<sub>1</sub>21), with unit-cell parameters a = 55.281, b = 55.281, c = 112.449 Å and a diffraction limit of 1.97 Å. Initial phasing of the trigonal crystals was successfully performed by the SIRAS method using Cu Kα radiation with the selenomethionine derivative as a heavy-atom derivative. The structure of the orthorhombic crystal form was solved by molecular replacement using the coordinates of the trigonal form.
Dorta R., Shimon L. J. W., Rozenberg H., Ben-David Y. & Milstein D. (2003) Inorganic Chemistry. 42, 10, p. 3160-3167
The synthesis of a new ligand system for mono- and bimetallic complexes based on a calixarene is described. Ligand BBPC (3, bis(bipyridine)-calix[4]arene) is obtained in three steps in 40% overall yield by first brominating one of the methyl groups of the 4,4-dimethyl-2,2-bipyridine in two steps and subsequently reacting it with p-tertbutylcalix[4]arene under basic conditions. Reaction of BBPC (3) with 2 equiv of [Rh(NBD)<sub>2</sub>]BF<sub>4</sub> or [Rh(NBD)(CH<sub>3</sub>CN)<sub>2</sub>]BF<sub>4</sub> (NBD = norbornadiene) produces the bimetallic compound BBPC[Rh(NBD)BF<sub>4</sub>]<sub>2</sub> (4). Treatment of the ligand with PdCl<sub>2</sub>(CH<sub>3</sub>CN)<sub>2</sub> leads to the isolation of the bimetallic complex BBPC[PdCl<sub>2</sub>]<sub>2</sub> (5). When the nickel precursor NiBr<sub>2</sub>(DME) (DME = dimethoxyethane) is reacted with BBPC, the bimetallic complex BBPC[NiBr<sub>2</sub>]<sub>2</sub> (6) is isolated which, upon crystallization from methanol, gives the mononuclear bis(bipyridine) complex BBPC[NiBr(OMe)] (7). Full characterization includes X-ray structural studies of complexes 4, 5, and 7. The bimetallic compounds 4 and 5 show metal to metal distances of 4.334, Å (for 4) and 3.224, Å (for 5). For all three complexes, unique molecular packing arrangements were found, based on hydrophobic/hydrophilic interactions.
Ben-Ari E., Gandelman M., Rozenberg H., Shimon L. J. W. & Milstein D. (2003) Journal of the American Chemical Society. 125, 16, p. 4714-4715
The cationic PNP-Ir(I)(cyclooctene) complex 1 (PNP = 2,6-bis-(di-tert-butyl phosphino methyl)pyridine) reacts with benzene at 25 °C to quantitatively yield the crystallographically characterized, square pyramidal, iridium phenyl hydride complex cis-(PNP)Ir(Ph)(H), 2, in which the hydride is trans to the vacant coordination site. The cationic complex 2 is stable to heating at 100 °C, in sharp contrast to the previously reported unstable neutral, isoelectronic (PCP)Ir(H)(Ph) (PCP = η<sup>3</sup>-2,6-(<sup>t</sup>Bu<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H<sub>3</sub>). Heating of 2 at 50 °C with other arenes results in arene exchange. Complex 1 activates C-H bonds of chloro- and bromobenzene with no C-halide oxidative addition being observed. Selective ortho C-H activation takes place, the process being directed by halogen coordination and being thermodynamically and kinetically favorable. The meta- and para-C-H activation products are formed at a slower rate than the ortho isomer and are converted to it. NMR data and an X-ray crystallographic study of the ortho-activated chlorobenzene complex, which was obtained as the only product upon heating of 1 with chlorobenzene at 60 °C, show that the chloro substituent is coordinated to the metal center.
Dorta R., Rozenberg H., Shimon L. J. W. & Milstein D. (2003) Chemistry - A European Journal. 9, 21, p. 5237-5249
Novel neutral and cationic Rh<sup>I</sup> and Ir<sup>I</sup> complexes that contain only DMSO molecules as dative ligands with S-, O-, and bridging S,O-binding modes were isolated and characterized. The neutral derivatives [RhCl(DMSO)<sub>3</sub>] (1) and [IrCl(DMSO)<sub>3</sub>] (2) were synthesized from the dimeric precursors [M<sub>2</sub>Cl<sub>2</sub>(coe)<sub>4</sub>] (M = Rh, Ir; COE = cyclooctene). The dimeric Ir<sup>I</sup> compound [Ir <sub>2</sub>Cl<sub>2</sub>(DMSO)<sub>4</sub>] (3) was obtained from 2. The first example of a square-planar complex with a bidentate S,O-bridging DMSO ligand, [(coe)(DMSO)Rh-(μ-Cl)(μ-DMSO)RhCl(DMSO)] (4), was obtained by treating [Rh<sub>2</sub>Cl<sub>2</sub>(coe)<sub>4</sub>] with three equivalents of DMSO. The mixed DMSO-olefin complex [IrCl(cod)(DMSO)] (5, COD = cyclooctadiene) was generated from [Ir<sub>2</sub>Cl<sub>2</sub>(cod) <sub>2</sub>]. Substitution reactions of these neutral systems afforded the complexes [RhCl(py)(DMSO)<sub>2</sub>] (6), [IrCl(py)(DMSO)<sub>2</sub>] (7), [IrCl(iPr<sub>3</sub>P)(DMSO)<sub>2</sub>] (8), [RhCl(dmbpy)(DMSO)] (9, dmbpy = 4,4-dimethyl-2,2-bipyridine), and [IrCl(dmbpy)(DMSO)] (10). The cationic O-bound complex [Rh(cod)(DMSO)<sub>2</sub>]BF<sub>4</sub> (11) was synthesized from [Rh(cod)<sub>2</sub>]BF<sub>4</sub>. Treatment of the cationic complexes [M(coe)<sub>2</sub>(O=CMe<sub>2</sub>)<sub>2</sub>]PF<sub>6</sub> (M = Rh, Ir) with DMSO gave the mixed S- and O-bound DMSO complexes [M(DMSO) <sub>2</sub>(DMSO)<sub>2</sub>]PF<sub>6</sub> (Rh = 12; Ir=in situ characterization). Substitution of the O-bound DMSO ligands with dmbpy or pyridine resulted in the isolation of [Rh(dmbpy)DMSO<sub>2</sub>]PF<sub>6</sub> (13) and [Ir(py)<sub>2</sub>(DMSO)<sub>2</sub>]PF<sub>6</sub> (14). Oxidative addition of hydrogen to [IrCl(DMSO)<sub>3</sub>] (2) gave the kinetic product fac-[Ir(H)<sub>2</sub>Cl(DMSO)<sub>3</sub>] (15) which was then easily converted to the more thermodynamically stable product mer-[Ir(H) <sub>2</sub>Cl(DMSO)<sub>3</sub>] (16). Oxidative addition of water to both neutral and cationic Ir<sup>I</sup> DMSO complexes gave the corresponding hydrido-hydroxo addition products syn-[(DMSO)<sub>2</sub>HIr(μ-OH) <sub>2</sub>(μ-Cl)IrH(DMSO)<sub>2</sub>] [IrCl<sub>2</sub>(DMSO) <sub>2</sub>] (17) and anti-[(DMSO)<sub>2</sub>(DMSO)HIr(μ-OH) <sub>2</sub>IrH(DMSO)<sub>2</sub>(DMSO)][PF<sub>6</sub>]<sub>2</sub> (18). The cationic [Ir(DMSO)<sub>2</sub>(DMSO)<sub>2</sub>(DMSO)<sub>2</sub>]PF <sub>6</sub> complex (formed in situ from [Ir(coe)<sub>2</sub>(O=CMe <sub>2</sub>)<sub>2</sub>]PF<sub>6</sub>) also reacts with methanol to give the hydrido-alkoxo complex syn-[(DMSO)<sub>2</sub>HIr(μ-OCH<sub>3</sub>) <sub>3</sub>IrH(DMSO)<sub>2</sub>]<sub>2</sub>]PF<sub>6</sub> (19). Complexes 1, 2, 4, 5, 11, 12, 14, 17, 18, and 19 were characterized by crystallography.
Dorta R., Konstantinovski L., Shimon L., Ben David D. Y. & Milstein D. (2003) European Journal of Inorganic Chemistry. 1, p. 70-76
The tetradentate ligand 3,6-bis(2-pyridyl)pyridazine (dppn) was treated with cationic Rh<sup>I</sup> precursors. The mononuclear complexes [Rh(dppn)(NBD)]BF<sub>4</sub> (1) and [Rh(dppn)(COD)]BF<sub>4</sub> (5) were obtained in quantitative yield when treating dppn with [Rh(NBD)<sub>2</sub>]BF<sub>4</sub> or [Rh(COD)<sub>2</sub>]BF<sub>4</sub> respectively. Treatment of 1 with a second equivalent of the metal precursor [Rh(NBD)(CH<sub>3</sub>CN)<sub>2</sub>]BF<sub>4</sub> led to the dinuclear complex [Rh<sub>2</sub>(dppn-H)(NBD)(η-C<sub>7</sub>H<sub>9</sub>) (CH<sub>3</sub>CN)<sub>2</sub>](BF<sub>4</sub>)<sub>2</sub> (2) [dppn-H = μ-C<sub>4</sub>HN<sub>2</sub>(C<sub>5</sub>H<sub>4</sub>N)<sub>2</sub>-3, 6], a mixed Rh<sup>I</sup>-Rh<sup>III</sup> complex. This complex arises from C-H activation of the pyridazine ring, followed by a unique rearrangement of the NBD ligand. Compound 2 was also obtained directly by treating dppn with 2 equiv. of [Rh(NBD)(CH<sub>3</sub>CN)<sub>2</sub>]BF<sub>4</sub>. The complex [Rh<sub>2</sub>(dppn-H)(NBD)(η<sup>1</sup>-C<sub>7</sub>H<sub>9</sub>) (CH<sub>3</sub>OH)<sub>2</sub>(CH<sub>3</sub>CN)](BF<sub>4</sub>)<sub>2</sub> (4) was obtained by dissolving 2 in methanol. Full characterization of compounds 1, 4 and 5 included an investigation by <sup>1</sup>H-<sup>15</sup>N GHMBC NMR spectroscopy and single-crystal X-ray structures of 1 and 4.
Cohen R., Rybtchinski B., Gandelman M., Shimon L. J. W., Martin J. M. L. & Milstein D. (2003) Angewandte Chemie - International Edition. 42, 17, p. 1949-1952
An unprecedented reaction : Dinitrogen pincer Rh complexes react with azines in a moderately catalytic fashion by \u201cnonsymmetrical\u201d N-N bond cleavage to the corresponding nitriles and imines (see scheme).
Shimon L., Rabinkov A., Miron T., Mirelman D., Wilchek M. & Frolow F. (2002) Acta Crystallographica Section D: Biological Crystallography. 58, 8, p. 1335-1337
The enzyme alliinase has been isolated from garlic bulbs and crystallized. The crystals belong to space group P2<sub>1</sub>, with unit-cell parameters a = 70.191, b = 127.006, c = 108.085 Å, β = 93.384°. They diffract to 2.2 Å at liquid-nitrogen temperature. Analysis of the Patterson self-rotation function suggests that the crystals contain two dimeric molecules per asymmetric unit.
Goikhman R., Aizenberg M., Ben-David Y., Shimon L. J. W. & Milstein D. (2002) Organometallics. 21, 23, p. 5060-5065
Rhodium and iridium complexes of the general formula (PP<sub>2</sub>)MX bearing the new triphosphine ligand <sup>i</sup>Pr<sub>2</sub>P(CH<sub>2</sub>)<sub>3</sub>P(Ph)(CH<sub>2</sub>) <sub>3</sub>P<sup>i</sup>Pr<sub>2</sub> (PP<sub>2</sub>) have been synthesized. Reactivity of the PP<sub>2</sub>MX complexes toward HSi(SEt)<sub>3</sub> was studied. Whereas (PP<sub>2</sub>)RhCl and (PP<sub>2</sub>)IrCl do not react with HSi(SEt)<sub>3</sub>, (PP<sub>2</sub>)RhH gives rise to the Rh(III) adduct [(PP<sub>2</sub>)Rh(H)<sub>2</sub>Si(SEt)<sub>3</sub>], and (PP<sub>2</sub>)RhMe (3) activates both the Si-H and the Si-S bonds of HSi(SEt)<sub>3</sub>, affording the Rh(I) complexes (PP<sub>2</sub>)RhSi(SEt)<sub>3</sub> (5) and (PP<sub>2</sub>)RhSEt (6). Only a few stable Rh(I) silyl complexes are known, and Si-S bond activation by transition-metal complexes has been rarely observed. The X-ray crystal structure of 5 exhibits a considerable distortion from square-planar geometry, the average angle between the trans-disposed ligands being 152.5°. In contrast to 3, (PP<sub>2</sub>)IrMe (8) forms a stable Ir(III) adduct with HSi(SEt)<sub>3</sub>, fac-[(PP<sub>2</sub>)Ir-(Me)(H)(Si(SEt)<sub>3</sub>)] (9). No Si-S activation was observed with 8. Thus, the reactivity of (PP<sub>2</sub>)-MX complexes toward HSi(SEt)<sub>3</sub> strongly depends on the nature of M and X.
Hermann D., Gandelman M., Rozenberg H., Shimon L. J. W. & Milstein D. (2002) Organometallics. 21, 5, p. 812-818
Reaction of the new highly electron-donating PNP ligand [2,6-bis-(di-tert-butylphosphi-nomethl)pyridine] (1) with [Rh(COE)<sub>2</sub>Cl]<sub>2</sub> (COE = cyclooctene) at room temperature resulted in formation of the neutral Rh(I) complex [Rh(PNP)Cl] (2). Unsaturated cationic complexes [Rh(PNP)(CH<sub>3</sub>CN)]BF<sub>4</sub> (3) and [Rh(PNP)(C<sub>2</sub>H<sub>4</sub>)]SO<sub>3</sub>CF<sub>3</sub> (4) were obtained in reaction of 1 with [(COE)<sub>2</sub>Rh(CH<sub>3</sub>CN)<sub>2</sub>]BF<sub>4</sub> and [(C<sub>2</sub>H<sub>4</sub>)<sub>2</sub>Rh(THF)<sub>2</sub>]SO<sub>3</sub>CF <sub>3</sub>, respectively. Upon reaction of the PNP ligand 1 with [Ir(COE)<sub>2</sub>Cl]<sub>2</sub>, facile vinylic C-H activation takes place, yielding the hydrido-vinyl complex [ClIr(PNP)(H)(C<sub>8</sub>H<sub>13</sub>)] (5). Also, coordination of ligand 1 to the cationic iridium complex [Ir(COD)<sub>2</sub>]BF<sub>4</sub> (COD = cyclooctadiene) in RCN (R = CH<sub>3</sub>, CH(CH<sub>3</sub>)<sub>2</sub>, C(CH<sub>3</sub>)<sub>3</sub>) led to iridium insertion into a vinylic C-H bond, resulting in complexes [(RCN)-Ir(PNP)(H)(C<sub>8</sub>H<sub>11</sub>)]BF<sub>4</sub> (6a-c). The hydrido-vinyl complexes 6a,c readily react with H<sub>2</sub> (2 atm) at room temperature, affording the iridium dihydride complexes [(RCN)Ir(PNP)-(H)<sub>2</sub>]BF<sub>4</sub> (R = CH<sub>3</sub>, C(CH<sub>3</sub>)<sub>3</sub>) (7a,b).
Shimon L., Peretz M., Goihberg E., Burstein Y. & Frolow F. (2002) Acta Crystallographica Section D: Biological Crystallography. 58, 3, p. 546-548
The tetrameric NADP<sup>+</sup>-dependent secondary alcohol dehydrogenase from Entamoeba histolytica has been crystallized in its apo form. The crystals belong to space group C222<sub>1</sub>, with unit-cell parameters a = 76.89, b = 234.24, c = 96.24 Å, and diffract to 1.9 Å at liquid-nitrogen temperature. Analysis of the Patterson self-rotation function shows that the crystals contain one dimer per asymmetric unit.
Bartfeld D., Shimon L. J. W., Couture G., Rabinovich D., Frolow F., Levanon D., Groner Y. & Shakked Z. (2002) Structure. 10, 10, p. 1395-1407
The Runt domain proteins are transcription regulators of major developmental pathways. Here we present the crystal structures of the Runt domain (RD) of the human protein RUNX1 and its DNA binding site in their free states and compare them with the published crystal structures of RD bound to DNA and to the partner protein CBFβ. We demonstrate that (1) RD undergoes an allosteric transition upon DNA binding, which is further stabilized by CBFβ, and that (2) the free DNA target adopts a bent-helical conformation compatible with that of the complex. These findings elucidate the mechanism by which CBFβ enhances RD binding to DNA as well as the role of the intrinsic conformation of the DNA target in the recognition process.
Dorta R., Rozenberg H., Shimon L. J. W. & Milstein D. (2002) Journal of the American Chemical Society. 124, 2, p. 188-189
The oxidative addition of water to novel Ir(I) DMSO complexes is described. IrCl(DMSO)3 (1) is synthesized in 90% yield when treating a toluene slurry of [Ir2Cl2(COE)4] (COE = cyclooctene) with excess DMSO. Its dimer, [Ir2Cl2(DMSO)4] (2) is obtained in 95% yield starting from 1. The cationic complex [Ir(DMSO)4]PF6 (6) is prepared in situ from [Ir(COE)2(OCMe2)2]PF6 (5). These complexes add water at room temperature, giving rise to the oxidative addition products syn-[(DMSO)2HIr(μ-OH)2(μ-Cl)IrH(DMSO)2] [IrCl2(DMSO)2] (3) and anti-[(DMSO)2(DMSO)HIr(μ-OH)2IrH(DMSO)2(DMSO)](PF6)2 (7), respectively. Reductive elimination in pyridine leads to quantitative isolation of mixed Ir(I) DMSO−pyridine complexes IrCl(py)(DMSO)2 (4) and [Ir(py)2(DMSO)2]PF6 (8), respectively. Compounds 1, 3, and 7 have been characterized by X-ray crystallography. 3 and 7 show dimeric structures with the hydroxo ligands bridging the iridium atoms and in 7 both O- and S-bonded DMSO ligands are present.
Dorta R., Shimon L. J. W., Rozenberg H. & Milstein D. (2002) European Journal of Inorganic Chemistry. 2002, 7, p. 1827-1834
Neutral and cationic Rh(dmbpy) systems (dmbpy = 4,4-dimethyl-2,2-bipyridine) were synthesized starting from different metal precursors. [RhCl(dmbpy)(DMSO)] (3) was obtained either from the ethylene precursor [RhCl(dmbpy)(C<sub>2</sub>H<sub>4</sub>)] (1) or directly from [Rh<sub>2</sub>Cl<sub>2</sub>(COE)<sub>4</sub>] (COE = cyclooctene) in DMSO. The neutral isocyanide complex [RhCl(dmbpy){CNC(CH<sub>3</sub>)<sub>3</sub>}] (4) was obtained by reaction of 1 with tert-butyl isocyanide. Reaction of dmbpy with [Rh(DMSO)<sub>4</sub>]PF<sub>6</sub> gave the corresponding cationic complex [Rh(dmbpy)(DMSO)<sub>2</sub>]PF<sub>6</sub> (5), and the cationic system [Rh(dmbpy){CNC(CH<sub>3</sub>)<sub>3</sub>}<sub>2</sub>]BF<sub>4</sub> (6) was prepared starting from [Rh(dmbpy)(HD)]BF<sub>4</sub> (2) (HD = 1,5-hexadiene). All of these complexes were found to activate the C-Cl bond in benzyl chloride leading to quantitative isolation of the corresponding Rh<sup>III</sup> complexes [RhCl<sub>2</sub>(CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>)(dmbpy)(DMSO)] (7), [RhCl<sub>2</sub>(CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>)(dmbpy) {CNC(CH<sub>3</sub>)<sub>3</sub>}] (9) [RhCl(CH<sub>2</sub>-C<sub>6</sub>H<sub>5</sub>)(dmbpy)(DMSO)<sub>2</sub>] PF<sub>6</sub> (10) and [RhCl(CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>)-(dmbpy){CNC (CH<sub>3</sub>)<sub>3</sub>}<sub>2</sub>]BF<sub>4</sub> (12). Oxidative addition of dichloromethane by complexes 3 and 5 yielded the corresponding chloromethyl complexes [RhCl<sub>2</sub>(CH<sub>2</sub>Cl)(dmbpy)(DMSO)] (8) and [RhCl(CH<sub>2</sub>Cl)(dmbpy)(DMSO)<sub>2</sub>]PF<sub>6</sub> (11). The reactivity of 3 towards oxygen led to the isolation of the peroxo Rh<sup>III</sup> complex [RhCl(O<sub>2</sub>)(dmbpy)(DMSO)] (13). Complexes 6, 8, 9 and 12 were characterized by X-ray crystallography.
Gauvin R. M., Rozenberg H., Shimon L. J. W. & Milstein D. (2001) Organometallics. 20, 9, p. 1719-1724
The new complex Os{1,3-(<sup>i</sup>Pr<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub> C<sub>6</sub>H<sub>3</sub>}(Cl)(PPh<sub>3</sub>) (2) was obtained from the reaction between the diphosphine {1,3-(<sup>i</sup>Pr<sub>2</sub> PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H<sub>4</sub>} (1) and OsCl<sub>2</sub>(PPh<sub>3</sub>)<sub>3</sub>. 2 reacts with H<sub>2</sub> to yield the dihydrido species Os{1,3-(<sup>i</sup>Pr<sub>2</sub> PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H<sub>3</sub>}(H)<sub>2</sub>(Cl) (PPh<sub>3</sub>) (3). Addition of 1 equiv of carbon monoxide to 2 led to the formation of Os{1,3-(<sup>i</sup>Pr<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub> C<sub>6</sub>H<sub>3</sub>}(CO)(Cl)(PPh<sub>3</sub>) (4), while in the presence of excess CO, the bis-carbonyl complex Os{1,3-(<sup>i</sup>Pr<sub>2</sub>PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub> H<sub>3</sub>}(CO)<sub>2</sub>-(Cl) (5) was formed. Both 2 and 5 were structurally characterized by X-ray diffraction studies. The reaction of OsCl<sub>2</sub>(PPh<sub>3</sub>)<sub>3</sub> (under hydrogen pressure) and OsHCl(PPh<sub>3</sub>)<sub>3</sub> with the diphosphine {1,3,5-(CH<sub>3</sub>)<sub>3</sub>-2,6-(<sup>i</sup>Pr<sub>2</sub> PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H} (6) led to the formation of the C-C activation products Os{3,5-(CH<sub>3</sub>)-2,6-(<sup>i</sup>Pr<sub>2</sub> PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H}(H<sub>2</sub>)(Cl)(PPh<sub>3</sub>) (7) and Os{3,5-(CH<sub>3</sub>)-2,6-(<sup>i</sup>Pr<sub>2</sub> PCH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H}(Cl)(PPh<sub>3</sub>) (8), respectively.
Khenkin A., Shimon L. & Neumann R. (2001) European Journal of Inorganic Chemistry. 3, p. 789-794
An antimony-substituted polyoxomolybdate, [PSb<sup>III</sup>(H<sub>2</sub>O) -Mo<sub>11</sub>O<sub>39</sub>]<sup>4-</sup>, of the α-Keggin structure, has been synthesized. Although the molecular structure is typical, we have found from the analysis of the X-ray diffraction data that the crystal is anisotropic with alignment of the molecular units so that the substituted antimony atoms are all directed along the polar c axis and on the same side of the molecular unit. UV/Vis, ESR and magnetic susceptibility data support a formulation of [PSb<sup>III</sup>(H<sub>2</sub>O)Mo<sub>11</sub>O<sub>39</sub>]<sup>4-</sup> whereby there is partial electron delocalization with some formation (10-20%) of Mo<sup>V</sup>. Oxidation of [PSb<sup>III</sup>(H<sub>2</sub>O)Mo<sub>11</sub>O<sub>39</sub>]<sup>4-</sup> with ozone or bromine yields the oxidized species [PSb<sup>V</sup>(O)Mo<sub>11</sub>O<sub>39</sub>]<sup>4-</sup> and [PSb<sup>V</sup>(Br)Mo<sub>11</sub>O<sub>39</sub>]<sup>3-</sup>. In the anaerobic oxydehydrogenation of alcohols, [PSb<sup>V</sup>(O)Mo<sub>11</sub>O<sub>39</sub>]<sup>4-</sup> is more active than [PSb<sup>V</sup>(Br)Mo<sub>11</sub>O<sub>39</sub>]<sup>3-</sup>. Catalytic aerobic oxidation of benzylic alcohols to aldehydes was also possible with no over-oxidation and formation of carboxylic̈ acids.
Rybtchinski B., Konstantinovsky L., Shimon L. J. W., Vigalok A. & Milstein D. (2000) Chemistry-A European Journal. 6, 17, p. 3287-3292
Reaction of the complex [Rh(coe)<sub>2</sub>(solv)<sub>n</sub>]BF<sub>4</sub> (coe = cyclooctene) with the phosphane 1-di-tert-butylphosphinomethyl-2,4,6-trimethylbenzene (1) results in selective C-H bond activation, yielding the spectroscopically characterized solvento complexes [(solv)<sub>n</sub>RhH{CH<sub>2</sub>C<sub>6</sub>H<sub>2</sub>(CH <sub>3</sub>)<sub>2</sub>-[CH<sub>2</sub>P(tBu)<sub>2</sub>]}]BF<sub>4</sub> (solv = acetone, 2a; THF, 2b; methanol, 2c). The stability of these complexes is solvent dependent, alcohols providing significant stabilization. Although cis-alkylrhodium hydride complexes containing labile ligands are generally unstable, 2a-c are stable at room temperature. Complex [(acetone)-(ketol)RhH{CH<sub>2</sub>C<sub>6</sub>H<sub>2</sub>(CH <sub>3</sub>)<sub>2</sub>[CH<sub>2</sub>P(t-Bu)<sub>2</sub>]}]BF<sub>4</sub> (2d, ketol = 4-hydroxy-4-methyl-2-pentanone, the product of acetone aldol condensation), crystallized from a solution of 2a in acetone and was structurally characterized. Unusual solvent- and temperature-dependent selectivity in reversible C-H bond elimination of these complexes, most probably controlled by a special mode of strong agostic interactions, is observed by spin saturation transfer experiments.
Shimon L., Pages S., Belaich A., Belaich J., Bayer E., Lamed R., Shoham Y. & Frolow F. (2000) Acta Crystallographica Section D: Biological Crystallography. 56, 12, p. 1560-1568
The crystal structure of the family IIIa cellulose-binding domain (CBD) from the cellulosomal scaffoldin subunit (CipC) of Clostridium cellulolyticum has been determined. The structure reveals a nine-stranded jelly-roll topology which exhibits distinctive structural elements consistent with family III CBDs that bind crystalline cellulose. These include a well conserved calcium-binding site, a putative cellulose-binding surface and a conserved shallow groove of unknown function. The CipC CBD structure is very similar to the previously elucidated family IIIa CBD from the CipA scaffoldin of C. thermocellum, with some minor differences. The CipC CBD structure was also compared with other previously described CBD structures from families IIIc and IV derived from the endoglucanases of Thermomonospora fusca and Cellulomonas fimi, respectively. The possible functional consequences of structural similarities and differences in the shallow groove and cellulose-binding faces among various CBD families and subfamilies are discussed.
Ashkenazi N., Vigalok A., Parthiban S., Ben David D. Y., Shimon L. J. W., Martin J. M. L. & Milstein D. (2000) Journal of the American Chemical Society. 122, 36, p. 8797-8798
Quinoid systems such as quinones, quinone methides, quinodimethanes, and quinodiimines have been widely investigated regarding their chemical, biological, and physical properties.1 Of special interest are their utility as charge transfer complexes due to the relatively low energy barrier between the ground and excited states. Some metal stabilized quinone methides have also been reported recently.2 Remarkably, no metallaquinone, that is, a compound in which one of the oxygen atoms of a quinone has been replaced by a metal, has hitherto been reported. Such a compound is expected to have a strong dipolar contribution to the excited state compared to its biradical nature in quinones. We know of only one example of a stable quinoid compound which contains a heavier element (phosphorus)3 instead of the oxygen.
Cohen R., van der Boom M. E., Shimon L. J. W., Rozenberg H. & Milstein D. (2000) Journal of the American Chemical Society. 122, 32, p. 7723-7734
Oxidative addition of aryl iodides ArI (Ar = (a) C<sub>6</sub>H<sub>5</sub>, (b) C<sub>6</sub>H<sub>4</sub>CF<sub>3</sub>, (c) C<sub>6</sub>H<sub>3</sub>(CF<sub>3</sub>)<sub>2</sub>, (d) C<sub>6</sub>H<sub>4</sub>CH<sub>3</sub>, (e) C<sub>6</sub>H<sub>4</sub>OCH<sub>3</sub>), to the PCP-type complex Rh(PPh<sub>3</sub>)[CH<sub>2</sub>C<sub>6</sub>H(CH<sub>3</sub>)<sub>2</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>] (1), yields the complexes Rh(Ar)[CH<sub>2</sub>C<sub>6</sub>H(CH<sub>3</sub>)<sub>2</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>](I) (2a-e). Compounds 2a-e undergo intramolecular methylene transfer from the bis-chelating ligand to the incoming aryl under mild conditions (room temperature) giving Rh(CH<sub>2</sub>-Ar)[C<sub>6</sub>H(CH<sub>3</sub>)<sub>2</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>](I) (3a-e). The methylene transfer, which is a unique sequence of sp<sup>2</sup>-sp<sup>3</sup> C-C bond reductive elimination and sp<sup>2</sup>-sp<sup>3</sup> C-C bond activation, was investigated kinetically (reaction 2a → 3a), yielding the activation parameters ΔH(+) = 17 ± 3 kcal/mol, ΔS(+) = -23 ± 4 eu. The rate-determining step of this reaction is the C-C reductive elimination rather than the C-C activation step. X-ray structural analysis of 2a and 3b demonstrates that the Rh atom is located in the center of a square pyramid with the aryl (2a) and the benzyl (3b) trans to the vacant coordination site. Reaction of the complex Rh(CH<sub>2</sub>C<sub>6</sub>H<sub>4</sub>CF<sub>3</sub>)[C<sub>6</sub>H<sub>3</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>](Br) (7c) with carbon nucleophiles (MeLi, PhLi, BzMgCl) leads to a competitive sp<sup>2</sup>-sp<sup>3</sup> and sp<sup>3</sup>-sp<sup>3</sup> C-C coupling, resulting in migration of a methylene or benzylidene into the bis-chelating ring and formation of the corresponding organic products, sp<sup>2</sup>-sp<sup>3</sup> C-C coupling was shown to be kinetically preferred over the sp<sup>3</sup>-sp<sup>3</sup> one, and the more electron-rich the benzyl ligand, the better the migratory aptitude observed. X-ray structural analysis of two benzyl migration products, complexes Rh(PPh<sub>3</sub>)[CH(C<sub>6</sub>H<sub>4</sub>CF<sub>3</sub>)C<sub>6</sub>H<sub>3</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>] (11) and Rh(PPh<sub>3</sub>)[CH(C<sub>6</sub>H<sub>5</sub>)C<sub>6</sub>H(CH<sub>3</sub>)<sub>2</sub>(CH<sub>2</sub>PPh<sub>2</sub>)<sub>2</sub>] (16), demonstrates that the rhodium atom is located in the center of a square planar arrangement where the PPh<sub>3</sub> ligand occupies the position trans to the methyne carbon of the benzylidene bridge. The methylene and benzylidene migration reaction is an important transformation for the regeneration of the methylene-donating moiety in the methylene-transfer process.
Vigalok A., Rybtchinski B., Shimon L. J. W., Ben-David Y. & Milstein D. (1999) Organometallics. 18, 5, p. 895-905
Protonation of rhodium and iridium complexes of formula ClM(CH3)[C6H(CH3)(2)(CH2P(t-Bu)(2))(2)] (M = Rh (1), Ir (3)) with a strong acid (HOTf, trifluoromethanesulfonic acid) results in clean formation of the new methylene arenium metal complexes ClM[CH2=C6H(CH3)(2)(CH2P(t-Bu)(2))(2)]+OTf- (M = Rh (2a), Ir (4), respectively), which have been fully characterized including an X-ray single-crystal analysis. This new method can be applied to complexes having both electron-donating and electron-withdrawing substituents in the aromatic ring. The methylene arenium complexes bear most of the positive charge in the ring, resulting in their high CH acidity. Deprotonation of these complexes with NEt3 gives the new metal xylylene complexes 12 (M = Rh) and 13 (M = Ir), which can be converted back to the methylene arenium complexes by reaction with HOTf. Reaction of the cationic complexes -OTf+Rh(R)[C6H(CH3)(2)(CH2P(t Bu)(2))(2)] (R = CH3, PhCH2) with CO gives the new alkyl sigma-arenium rhodium complexes Rh(CO)[R-C6H(CH3)(2)(CH2P(t-Bu)(2))(2)]+OTf- (R = CH3 (9a), PhCH2 (9b)). On the basis of the NMR data, the X-ray crystal structure analysis, and the reactivity, these Rh complexes were shown to have much less positive charge in the ring as compared to the methylene arenium complexes, most probably due to stabilization of an arene form by an agostic interaction of the arene-alkyl C-ipso-C bond with the metal center. The nature of the reported phenomena is discussed. The interconversion of the methylene arenium and alkyl sigma-arenium metal complexes is also presented.
Vigalok A., Shimon L. J. W. & Milstein D. (1998) Journal of the American Chemical Society. 120, 3, p. 477-483
The quinone methide (QM) rhodium complex of 3,5-bis(di-tert-butylphosphinomethyl-2,6-dimethyl-4-methylene-3,5-cyclohexadien -1-one (L) (1) was protonated by trifluromethanesulfonic acid (triflic acid) at the quinonoid carbonyl group giving the unique methylene arenium complex (Cl)Rh[LH<sup>+</sup>]CF<sub>3</sub>SO<sub>3</sub><sup>-</sup> (2). Complexes 2 and its (trimethyl)silyl analogue (3) were fully characterized spectroscopically, and complex 2 was also characterized by single-crystal X-ray analysis. The crystallographic studies on 2 have revealed that the positive charge is delocalized between the carbon atoms of the ring with most of it being at the para- and ortho-carbon atoms. The electron deficient QM complex (CO)Rh<sup>+</sup>[L] CF<sub>3</sub>SO<sub>3</sub><sup>-</sup> (4), which has also been crystallographically characterized, is less basic, requiring excess of triflic acid to obtain the methylene arenium complex (CO)Rh<sup>+</sup>[LH<sup>+</sup>]2CF<sub>3</sub>SO<sub>3</sub><sup>-</sup> (5), demonstrating a dramatic effect of the electron density on the metal center on the stability of the methylene arenium species. When 1 was reacted with 2-3 equiv of MeLi formation of two complexes, MeRh[3,5-bis(di-tert-butylphosphinomethyl)-2,6-dimethyl-4-methylene-3,5 -cyclohexadien-1-en] (6) and its ortho-xylylene isomer (7), took place. Complexes 6 and 7 represent the first example of thermally stable xylylenes coordinated via only one of the exocyclic double bonds. Both 6 and 7 undergo protonation by CF<sub>3</sub>SO<sub>3</sub>H giving as a single product the arenium complex CF<sub>3</sub>SO<sub>3</sub>Rh[3,5-bis(di-tert-butylphosphinomethyl)-1, 2,6-trimethyl-4-methylene-3,5-cyclohexadienyl]<sup>+</sup>CF<sub>3</sub>SO<sub>3</sub><sup>-</sup> (8). <sup>13</sup>C NMR studies performed on the arenium complexes shows no para-substituent effect on the chemical shift of the coordinated CH<sub>2</sub> group and that this group does not participate in the positive charge delocalization. Thus, the reported methylene arenium compounds can be viewed as a resonance form of a benzyl cation stabilized by metal complexation.
Vigalok A., Uzan O., Shimon L. J. W., Ben David Y., Martin J. M. L. & Milstein D. (1998) Journal of the American Chemical Society. 120, 48, p. 12539-12544
Reaction of the ligand 1,3-bis((di-tert-butylphosphino)methyl)benzene (1a) with the [RhCO]<sup>+</sup> fragment in THF resulted in clean formation of the crystallographically characterized his-chelated complex 2a which contains an η<sup>2</sup> agostic Rh C-H bond. Both the NMR data and the X-ray crystal structure show strong interaction between the metal center and the agostic C-H bond, which results in high acidity of the agostic proton. Reaction of 2a with a weak organic base (NEt<sub>3</sub> or collidine) affords the known cyclometalated complex 3. Reaction of the new ligand 1,3-bis((di-tert- butylphosphino)methyl)-4,5,6-trimethoxybenzene (1b) with the [RhCO]<sup>+</sup> fragment in THF gives the analogous to 2a agostic complex 2b. Analysis of the NMR data and the reactivity of both 2a and 2b showed that there is very little, if any, contribution of a metal arenium structure. This interpretation is supported by B3LYP/LANL2DZ density functional calculations on model compounds. Thus, deprotonation of η<sup>2</sup> aromatic C-H agostic complexes can be proposed as an alternative route to electrophilic metalation of aromatic compounds.
van der Boom M. E., Liou S., Ben-David Y., Shimon L. J. W. & Milstein D. (1998) Journal of the American Chemical Society. 120, 26, p. 6531-6541
Reaction of [RhCl(C<sub>8</sub>H<sub>14</sub>)<sub>2</sub>]<sub>2</sub> (C<sub>8</sub>H<sub>14</sub> = cyclooctene) with 2 equiv of the aryl methyl ether phosphine 1 in C<sub>6</sub>D<sub>6</sub> results in an unprecedented metal insertion into the strong sp<sup>2</sup>-sp<sup>3</sup> aryl-O bond. This remarkable reaction proceeds even at room temperature and occurs directly, with no intermediacy of C-H activation or insertion into the adjacent weaker ArO-CH<sub>3</sub> bond. Two new phenoxy complexes (8 and 9), which are analogous to the product of insertion into the ArO-CH<sub>3</sub> bond (had it taken place) were prepared and shown not to be intermediates in the Ar-OCH<sub>3</sub> bond cleavage process. Thus, aryl-O bond activation by the nucleophilic Rh(I) is kinetically preferred over activation of the alkyl-O bond. The phenoxy Rh(I)-η<sup>1</sup>-N<sub>2</sub> complex (8) is in equilibrium with the crystallographically characterized Rh(I)-μ-N<sub>2</sub>-Rh(I) dimer(12). Reaction of [RhClC<sub>8</sub>H<sub>14</sub>)<sub>2</sub>]<sub>2</sub> with 2 equiv of the aryl methyl ether phosphine 2, PPh<sub>3</sub>, and excess HSiR<sub>3</sub> (R = OCH<sub>2</sub>CH<sub>3</sub>, CH<sub>2</sub>CH<sub>3</sub>) results also in selective metal insertion into the aryl-O bond and formation of (CH<sub>3</sub>O)SiR<sub>3</sub>. Thus, transfer of a OCH<sub>3</sub> group from carbon to silicon was accomplished, showing that hydrosilation of an unstrained aryl-O single bond by a primary silane is possible. The selectivity of C-O bond activation is markedly dependent on the transition-metal complex and the alkyl group involved, allowing direction of the C-O bond activation process at either the aryl-O or alkyl-O bond. Thus, contrary to the reactivity of the rhodium complex, reaction of NiI<sub>2</sub> or Pd(CF<sub>3</sub>CO<sub>2</sub>)2 with 1 equiv of 1 in ethanol or C<sub>6</sub>D<sub>6</sub> at elevated temperatures results in exclusive activation of the sp<sup>3</sup>-sp<sup>3</sup> ArO-CH<sub>3</sub> bond, while reaction of the analogous aryl ethyl ether 4 and Pd(CF<sub>3</sub>CO<sub>2</sub>)2 results in both sp<sup>3</sup>-sp<sup>3</sup> and sp<sup>2</sup>-sp<sup>3</sup> C-O bond activation. The resulting phenoxy Pd(II) complex (18) is fully characterized by X-ray analysis. Heating the latter under mild dihydrogen pressure results in hydrodeoxygenation to afford an aryl-Pd(II) complex (19).
Bayer E., Shimon L., Shoham Y. & Lamed R. (1998) Journal of Structural Biology. 124, 2-3, p. 221-234
The cellulosome is a macromolecular machine, whose components interact in a synergistic manner to catalyze the efficient degradation of cellulose. The cellulosome complex is composed of numerous kinds of cellulases and related enzyme subunits, which are assembled into the complex by virtue of a unique type of scaffolding subunit (scaffoldin). Each of the cellulosomal subunits consists of a multiple set of modules, two classes of which (dockerin domains on the enzymes and cohesin domains on scaffoldin) govern the incorporation of the enzymatic subunits into the cellulosome complex. Another scaffoldin module - the cellulose-binding domain - is responsible for binding to the substrate. Some cellulosomes appear to be tethered to the cell envelope via similarly intricate, multiple-domain anchoring proteins. The assemblage is organized into dynamic polycellulosomal organelles, which adorn the cell surface. The cellulosome dictates both the binding of the cell to the substrate and its extracellular decomposition to soluble sugars, which are then taken up and assimilated by normal cellular processes.
Shimon L., Frolow F., Yaron S., Bayer E., Lamed R., Morag E. & Shoham Y. (1997) Acta Crystallographica Section D: Biological Crystallography. 53, 1, p. 114-115
Recombinant cohesin-2, a unique type of protein-recognition domain from the cellulosome of Clostridium thermocellum, has been crystallized by the hanging-drop vapor-diffusion method. The crystals are monoclinic, space group C2 with unit-cell dimensions a = 79.91, b = 47.86, c = 51.13 Å, β = 126.77. There is most likely to be one molecule per asymmetric unit, corresponding to a packing density of 2.16 Å<sup>3</sup> Da<sup>-1</sup>. The crystals diffract to beyond 2.3 Å on a conventional laboratory rotating anode source.
Gandelman M., Vigalok A., Shimon L. J. W. & Milstein D. (1997) Organometallics. 16, 18, p. 3981-3986
Reaction of the new aromatic aminophosphine ligand 1-((diethylamino)methyl)-3-((di-tertbutylphosphino)methyl)-2,4,6- trimethylbenzene (4) with [Rh(COE)<sub>2</sub>Cl]<sub>2</sub> (COE = cyclooctene) or with [Rh(ethylene)<sub>2</sub>Cl]<sub>2</sub> at room temperature results in selective carbon-carbon bond activation, yielding the complex ClRh(CH<sub>3</sub>)[C<sub>6</sub>H(CH<sub>3</sub>)<sub>2</sub>(CH <sub>2</sub>N(C<sub>2</sub>H<sub>5</sub>)<sub>2</sub>)(CH <sub>2</sub>P(t-Bu)<sub>2</sub>)] (5). No competing C-H activation was observed during the course of the reaction. When 4 was reacted with (COD)PtCl<sub>2</sub> (COD = cyclooctadiene), selective C-H activation of the methyl group situated between the phosphine and amine groups took place, with concomitant intramolecular H transfer to the amine ligand, resulting in the zwitterionic Pt(II) complex Cl<sub>2</sub>PtCH<sub>2</sub>(C<sub>6</sub>H(CH<sub>3</sub>) <sub>2</sub>(CH<sub>2</sub>NH(C<sub>2</sub>H<sub>5</sub>)<sub>2</sub>(CH <sub>2</sub>P(t-Bu)<sub>2</sub>) (11).
Shimon L., Bayer E., Morag E., Lamed R., Yaron S., Shoham Y. & Frolow F. (1997) Structure. 5, 3, p. 381-390
Background: The scaffoldin component of the cellulolytic bacterium Clostridium thermocellum is a non-hydrolytic protein which organizes the hydrolytic enzymes in a large complex, called the cellulosome. Scaffoldin comprises a series of functional domains, amongst which is a single cellulose-binding domain and nine cohesin domains which are responsible for integrating the individual enzymatic subunits into the complex. The cohesin domains are highly conserved in their primary amino acid sequences. These domains interact with a complementary domain, termed the dockerin domain, one of which is located on each enzymatic subunit. The cohesin-dockerin interaction is the crucial interaction for complex formation in the cellulosome. The determination of structural information about the cohesin domain will provide insights into cellulosome assembly and activity. Results: We have determined the three-dimensional crystal structure of one of the cohesin domains from C. thermocellum (cohesin 2) at 2.15 Å resolution. The domain forms a nine-stranded β sandwich with a jelly-roll topology, somewhat similar to the fold displayed by its neighboring cellulose-binding domain. Conclusions: The compact nature of the cohesin structure end its lack of a defined binding pocket suggests that binding between the cohesin and dockerin domains is characterized by interactions between exposed surface residues. As the cohesin-dockerin interaction appears to be rather nonselective, the binding face would presumably be characterized by surface residues which exhibit both intraspecies conservation and interspecies dissimilarity. Within the same species, unconserved surface residues may reflect the position of a given cohesin domain within the scaffoldin subunit, its orientation and interactions with neighboring domains.
Yaron S., Shimon L., Frolow F., Lamed R., Morag E., Shoham Y. & Bayer E. (1996) Journal of Biotechnology. 51, 3, p. 243-249
The cellulosome of the cellulolytic bacterium, Clostridium thermocellum, is a multi-enzyme complex in which the enzymatic (cellulolytic) subunits are attached to a unique nonhydrolytic subunit called scaffoldin. The attachment is mediated by two mutually interacting domains: namely, multiple cohesin domains on the scaffoldin subunit and a dockerin domain on each of the enzymatic subunits. Knowledge of the three-dimensional structure of each of the interacting components would be critical to a better understanding of the cohesin-dockerin interaction at the molecular level. In this report, we describe the purification of one of the nine cohesin domains of the scaffoldin subunit from C. thermocellum. A DNA segment containing the cohesin 2 sequence was fused to a hexa-histidine tag, and the resultant construct was expressed in Escherichia coli. The expressed peptide was efficiently isolated by metal-chelate affinity chromatography. The purified recombinant form of the cohesin was crystallized pending determination of its structure.
Vigalok A., Shimon L. J. W. & Milstein D. (1996) Chemical Communications. 1996, 14, p. 1673-1674
A unique, unexpectedly stable rhodium complex containing hydride, alkene and dioxygen ligands in cis-positions to each other is synthesized and fully characterized spectroscopically and crystallographically.
van der Boom M. E., Gozin M., Ben-David Y., Shimon L. J. W., Frolow F., Kraatz H. & Milstein D. (1996) Inorganic Chemistry. 35, 24, p. 7068-7073
The coordination behavior prior to C-M bond formation of the chelating aromatic PCP substrate DPPMH (3; DPPMH = l,3-bis((diphenylphosphino)methylene)mesitylene) has been studied in order to determine the factors which control the complex formation of such ligands. Reacting 3 with (RCN)<sub>2</sub>MCl<sub>2</sub> (R = Me, Ph; M = Pd, Pt) and (COD)PtX<sub>2</sub> (X = Cl, Me; COD = 1,5-cyclooctadiene) resulted in the formation of several 8- and 16-membered mono- and binuclear palladium(II) and platinum(II) macrocycles: trans-[(DPPMH)PdCl<sub>2</sub>]<sub>2</sub> (5), trans-[(DPPMH)-PtCl<sub>2</sub>]<sub>2</sub> (6), cis-(DPPMH)PtCl<sub>2</sub> (7), cis-(DPPMH)PtMe<sub>2</sub> (8), and cis-[(DPPMH)PtMe<sub>2</sub>]<sub>2</sub> (9). Compounds 5-9 were fully characterized using NMR, FAB-MS, FD-MS, elemental analysis, and X-ray crystallography. Thermolysis of the bimetallic trans-[(DPPMH)PtCl<sub>2</sub>]<sub>2</sub> (6) results in the formation of the monomeric cis-(DPPMH)PtCl<sub>2</sub> (7). The product formation depends on the neutral- (nitriles or COD) and anionic ligands (Cl and CH<sub>3</sub>) of the metal precursor. The molecular structures of trans-[(DPPMH)PdCl<sub>2</sub>]<sub>2</sub> (5) and cis-[(DPPMH)PtMe<sub>2</sub>]<sub>2</sub> (9) have been determined by complete single-crystal diffraction studies. Crystal data for 5: monoclinic, space group P2<sub>1</sub> /n with a = 14.547(3) Å, b = 17.431(4) Å, c = 27.839 (5) Å, β= 99.56(2)°, V = 6961(3) Å<sup>3</sup>, and Z = 4. The structure converged to R = 0.048 and R<sub>w</sub> = 0.049. Crystal data for 9: monoclinic, space group P2<sub>1</sub>/n with a = 19.187(4) Å, b = 19.189(4) Å c = 20.705(2) Å, β= 103.41(3)°, V = 7415(3) Å<sup>3</sup>, and Z = 4. The structure refinement converged to R = 0.0977 and R<sub>w</sub> = 0.2212.
van der Boom M. E., Liou S., Shimon L. J. W., Ben-David Y. & Milstein D. (1996) Organometallics. 15, 10, p. 2562-2568
The mechanism of the selective formation of the new benzylic mono- and bicyclometalated platinum(II) complexes 2a,b and 3b has been studied. Monitoring the initial sp<sup>3</sup> C-H activation of the ligand DIPPIDH (α<sup>2</sup>-(diisopropylphosphino)isodurene; 1) and (1,5-cyclooctadiene)dimethylplatinum(II) ((COD)PtMe<sub>2</sub>) at room temperature by <sup>31</sup>P{<sup>1</sup>H} NMR reveals that, after displacement of 1,5-cyclooctadiene, the complex cis-(DIPPIDH)(DIPPID)-PtMe (2a) is formed selectively by oxidative addition of a benzylic C-H bond and subsequent reductive elimination of CH<sub>4</sub>. This reaction is controlled by electronic factors. Heating of 2a results in isomerization to the thermodynamically more stable isomer trans-(DIPPIDH)-(DIPPID)PtMe (2b) as well as the formation of the double-C-H activated complex trans-(DIPPID)<sub>2</sub>Pt (3b) with liberation of CH<sub>4</sub> in parallel pathways. Continuous heating results in the quantitative formation of the thermally stable 3b. Mechanistically, the second C-H activation proceeds analogously to the first one. The molecular structure of 3b, possessing two six-membered metallacycles, two methylene bridges, and two phosphines in mutually trans positions, was determined by complete single-crystal diffraction studies.
Goikhman R., Aizenberg M., Shimon L. J. W. & Milstein D. (1996) Journal of the American Chemical Society. 118, 44, p. 10894-10895
The generation of compounds containing multiply bonded silicon is of much current interest.1,2 Silanones (i.e., compounds containing a silicon−oxygen double bond), although not isolated, are being generated as short-lived intermediates, normally using elaborate procedures for preparation and decomposition of suitable precursors.2 Since the trapping of the generated silanones and their incorporation into other molecules may be a synthetically very useful approach in organosilicon chemistry, we chose to study the possibility of generation of silanones from relatively simple starting materials under mild conditions using transition metal complexes.
Shimon L., Vaida M., Frolow F., Lahav M., Leiserowitz L., Weissinger-Lewin Y. & McMullan R. (1993) Faraday Discussions. 95, p. 307-327
Principles are outlined for symmetry lowering of a mixed crystal composed of host and tailor-made additive molecules, based on selective occlusion of the latter through a subset of surface sites of the growing crystal, the symmetry of the surface generally being lower than that of the bulk. A survey is given of the various methods and approaches used to detect the reduction in symmetry. These include changes in crystal morphology, detection of enantiomeric segregation of chiral additives in 'centrosymmetric' crystals, generation of second-harmonic optical signals, optical birefringence, asymmetric photoreactions in the crystalline state and X-ray and neutron diffraction. The last two methods are applied to mixed crystals of cinnamamide (host) and thienylacrylamide (additive). The diffraction analysis demonstrated that the mixed crystals are composed of six sectors of reduced symmetry, from monoclinic centrosymmetric P2<sub>1</sub>/c to triclinic P1 in four sectors and possibly Pc in the remaining two. The X-ray diffraction data were not sufficiently accurate to permit assignment of the absolute structures of the P1 sectors with the use of anomalous X-ray scattering. Thus, by this method one could not ascertain the absolute orientation of the guest molecules on the surface sites through which they were selectively occluded. This ambiguity was resolved by assignment of the absolute configuration of the chiral heterophotodimers, between host and guest, in enantiomeric excess in the P1 sectors, after irradiation with UV light. These results led to the definite conclusion that the selective occlusion of thienylacrylamide arises from a replacement of attractive C-H⋯π (electron) interactions between host molecules by repulsive sulfur (lone-pair electron)⋯π (electron) interactions between guest and host at the crystal surfaces.
