Computational chemistry Publications

While discussing the vibrational radiative cooling of isolated cluster molecules, it is common to apply statistical models based on the density of vibrational states and calculated transition strengths. In the current work, we put this assumption to the test by studying the cooling rates of isolated Al⁻₅ ions across very long timescales ranging up to 2000 s. To this end, we stored Al⁻₅ ions in the Cryogenic Storage Ring (CSR) and monitored their internal excitation by laser-induced delayed electron emission. We find that once the internal energy drops below the first electronically excited state, the cooling rates scale linearly with energy. Our results are consistent with the calculated vibrational relaxation rates through the emission of infrared photons, based on the harmonic cascade model, thus validating quantitatively the assumption of a statistical cooling process for the relaxation of small cluster molecules with infrared-active vibrational modes.

Organic electrosynthesis offers a direct, electricity-driven strategy for constructing complex molecular structures in a more sustainable and innovative manner. However, even with the precise redox control that electrochemistry affords, steering highly reactive intermediates along a single productive pathway remains a central challenge, particularly when multiple mechanistic manifolds are accessible. Herein, we demonstrate that the identity of the supporting electrolyte dictates the selectivity of electro-reductive olefin coupling, directing the transformation toward either exclusively linear or exclusively branched products. Radical probes, CV, SEM, ssNMR, EPR, and DFT clarify these distinct pathways. Ammonium salts preserve the terminal spin bias of the styrene radical anion, promoting solution-phase radical addition for linear products. Lithium salts instead form a Li-rich interphase that drives benzylic spin localization and channels surface-confined radical coupling to yield branched products. This platform streamlines access to pharmaceutical-relevant scaffolds and reveals previously underexplored polar hydrofunctionalization of conjugated olefins. These findings establish electrolyte-controlled interfacial organization as a powerful lever to control product selectivity in organic electrosynthesis.

Precise control over crystal morphology is a longstanding challenge in materials science, as crystal shape governs optical, mechanical, and electronic properties. In contrast, living organisms achieve remarkable control over crystal morphology, though the underlying mechanisms are not fully understood. Among the most common organic materials are guanine crystals, notable for their plate-like morphology and high anisotropic refractive index, arising from the stacking of hydrogen-bonded molecular layers along the (100) plane. Here we show that simple synthetic polymers not only reproduce this biogenic plate-like form in vitro but also expand the accessible morphology space to prisms and needles by systematically varying i) multivalent interactions, ii) functional-group identity, and iii) polarity and hydrogen-bonding capacity. Using microscopy, spectroscopy, and molecular dynamics simulations, we find that carbonyl-bearing polymers selectively adsorb to the (100) stacking face, cap layer addition along the a-axis, and yield large plates indistinguishable from biogenic crystals. In contrast, reducing carbonyl polarity, increasing steric-bulk, or introducing highly-polar groups redirect adsorption and produces bulkier prisms or slender needles. Simulations corroborate facet selectivity, identify contact motifs involving carbonyl oxygens and adjacent methylenes. Together, these findings provide design principles for sculpting organic crystals and suggest analogous interactions exploited by biological scaffolds to orchestrate guanine assembly.

The diastereoselective semireduction of alkynes to alkenes is a powerful transformation in synthetic chemistry, yet catalytic methods for trans-selective (E) alkyne reduction remain limited. Herein, we introduce a fundamentally new approach for the highly selective trans-semireduction of internal alkynes, enabled by a cobalt-catalyzed electrochemical radical pathway. This method offers a broad substrate scope, accommodating alkynes with diverse electronic and steric profiles, and displays exceptional chemoselectivity and functional group tolerance. The methodology was extended to isotopically labeled trans-deuteration and demonstrated excellent chemoselectivity in substrates containing multiple alkyne motifs. Mechanistic studies, including cyclic voltammetry, UV-vis spectroelectrochemistry, and DFT calculations, support a dual catalytic cycle involving electrochemical Co-H formation and a subsequent organometallic radical pathway. Insights from this mechanism guided the development of a complementary chemical oxidative protocol, enabling access to E-alkenes from substrates that are otherwise unreactive under electroreductive conditions. This work introduces a fundamentally new and general strategy for accessing trans-alkenes from alkynes via cobalt catalysis while opening a new avenue for radical-based alkyne functionalization.

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.

We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales inaccessible in standard simulations. We recently showed that stochastic resetting can accelerate molecular simulations that exhibit broad transition time distributions. However, standard stochastic resetting does not exploit any information about the reaction progress. For a model system and chignolin in explicit water, we demonstrate that an informed resetting protocol leads to greater accelerations than standard stochastic resetting in molecular dynamics and Metadynamics simulations. This is achieved by resetting only when a certain condition is met, e.g., when the distance from the target along the reaction coordinate is larger than some threshold. We use these accelerated simulations to infer important kinetic observables such as the unbiased mean first-passage time and direct transit time. For the latter, Metadynamics with informed resetting leads to speedups of 2-3 orders of magnitude over unbiased simulations with relative errors of only ∼35-70%. Our work significantly extends the applicability of stochastic resetting for enhanced sampling of molecular simulations.

Channelrhodopsins, light-gated cation channels, enable precise control of neural cell depolarization or hyperpolarization with light in the field of optogenetics. This study integrates time-resolved serial crystallography and atomistic molecular dynamics (MD) simulations to resolve the structural changes during C1C2 channelrhodopsin activation. Our observations reveal that within the crystal environment, C1C2 predominantly remains in a light-activated state with characteristics of the M₃₉₀ intermediate. Here, rearrangement of retinal within its binding pocket partially opens the central gate toward the extracellular vestibule. These structural changes initiate channel opening but were insufficient to allow K⁺ flow. Adjusting protonation states to represent the subsequent N₅₂₀ intermediate in our MD simulations induced further conformational changes, including rearrangements of transmembrane helices 2 and 7, that opened the inner gate and the putative ion-translocation pathway. This allowed spontaneous cation conduction with low conductance, aligning with experimental findings. Our findings provide critical structural insights into key intermediates of the channel opening mechanism, enhancing our understanding of ion conduction and selectivity in channelrhodopsins at an atomistic level.

Chrimson is a naturally occurring channelrhodopsin with one of the most red-shifted absorption maxima (λ_max = 590 nm). This unique absorption makes it an ideal candidate for noninvasive optogenetic applications. The origin of the absorption maximum is thought to stem from a single deprotonated counterion near the Schiff base. However, it remains unclear which of the two potential counterions, E165 and D295, is protonated. In addition, a third titratable residue (E132) near the chromophore may also play a role in the spectral tuning mechanism. A single mutation from serine to alanine (S169A) further red-shifts the absorption maximum to 608 nm. Here we elucidate the mechanism behind the red-shifted absorption maximum using classical molecular dynamics simulations in tandem with hybrid QM/MM simulations. We found that protonation of both E165 and E132 leads to the correct experimental absorption trend for the wild type. This was further validated for the S169A mutant. The derived understanding of the spectral shift will guide the experimental design of red-shifted microbial rhodopsins.

Despite extensive research on carotenoids and microbial rhodopsins in aquatic environments, a fundamental understanding of the binding requirements of carotenoids that serve as auxiliary light-harvesting antennas for rhodopsins is still lacking. Our recent discovery of 3-hydroxylated xanthophyll-binding proteorhodopsins and xanthorhodopsins prompted us to investigate the role of keto and hydroxy functional groups in carotenoid binding to rhodopsins and their influence on energy transfer to the retinal chromophore. In this study, we examined the binding of 12 carotenoids to rhodopsin Kin4B8 (a protein of the xanthorhodopsin family, GenBank: OP056329) and assessed the energy transfer between the carotenoid and the retinal chromophore. We found that 3-hydroxylated xanthophylls were the most effective light-harvesting antennas among the carotenoids studied. While 4-ketocarotenoids also bound to the protein, their energy transfer efficiency was significantly reduced. In contrast, the presence of a 4-hydroxy group or the substitution of the β-ionone ring by an ε-ionone ring completely prevented binding. Furthermore, mutagenesis studies of Kin4B8 suggest that specific residues play a key role in the selective binding of carotenoids. These findings provide valuable insights into the structural determinants of rhodopsin-carotenoid interactions, which may aid in predicting the recruitment of various carotenoid antennas by retinal proteins.

The search for new materials to fabricate electronic devices mainly targets composites of metals, metal oxides, organic molecules, and polymers. We demonstrate here the fabrication and operation of a multilevel-per-bit metallo-organic memory cell (MOMC). This conceptually new memory cell has dual functionality. Information can be written and stored electrochemically and read out both electrochemically and optically. An electrochemical readout will reset the device to its ground state (read-while-write), whereas an optical readout can be continuous. The use of a nanoscale trilayer of electrochromically active ruthenium, iron, and osmium polypyridyl complexes resulted in up to four distinct states that can be addressed by applying different potentials. The information stored in the MOMC was used as input to an integrated circuit (IC), and it was visualized using light-emitting diodes (LEDs). These findings show the potential of metallo-organic materials to design hybrid ICs.

Fluorine electron-nuclear double resonance (¹⁹F ENDOR) has recently emerged as a valuable tool in structural biology for distance determination between F atoms and a paramagnetic center, either intrinsic or conjugated to a biomolecule via spin labeling. Such measurements allow access to distances too short to be measured by double electron-electron resonance (DEER). To further extend the accessible distance range, we exploit the high-spin properties of Gd(III) and focus on transitions other than the central transition (|−1/2⟩ ↔ |+1/2⟩), that become more populated at high magnetic fields and low temperatures. This increases the spectral resolution up to ca. 7 times, thus raising the long-distance limit of ¹⁹F ENDOR almost 2-fold. We first demonstrate this on a model fluorine-containing Gd(III) complex with a well-resolved ¹⁹F spectrum in conventional central transition measurements and show quantitative agreement between the experimental spectra and theoretical predictions. We then validate our approach on two proteins labeled with ¹⁹F and Gd(III), in which the Gd-F distance is too long to produce a well-resolved ¹⁹F ENDOR doublet when measured at the central transition. By focusing on the |−5/2⟩ ↔ |−3/2⟩ and |−7/2⟩ ↔ |−5/2⟩ EPR transitions, a resolution enhancement of 4.5- and 7-fold was obtained, respectively. We also present data analysis strategies to handle contributions of different electron spin manifolds to the ENDOR spectrum. Our new extended ¹⁹F ENDOR approach may be applicable to Gd-F distances as large as 20 Å, widening the current ENDOR distance window.

While individual single-wall carbon nanotubes (SWCNTs) have remarkable strength and electrical conductivity, SWCNT networks fabricated from dispersions have inferior properties due to nanotube bundling, limiting the potential applications of SWCNT materials. Herein, a common dye molecule (purpurin) is used to exfoliate SWCNTs via noncovalent functionalization and to fabricate SWCNT materials by a simple solution-based process. The advantageous noncovalent interactions result in efficient exfoliation and metallic SWCNT enrichment, affording SWCNT materials with high mechanical robustness and electrical conductivity. This method is used to prepare mechanically robust SWCNT films and flexible transparent conductive electrodes.Purpurin, a common dye molecule, is utilized to efficiently exfoliate single-wall carbon nanotubes (SWCNTs) in an aqueous solution. The advantageous noncovalent interactions result in metallic SWCNT enrichment, affording the fabrication of flexible, robust, and highly electrical conductive SWCNT networks. Transparent conductive electrodes based on those networks show excellent optoelectronic performance suitable for application in touch screens and LEDs.image

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.

In a previous study, it was observed that survivability was low when attempting to cryopreserve sperm cells in a nanoliter-sized droplet protected under soybean oil, in stark contrast to the high survival rates in milliliter-sized droplets. In this study, infrared spectroscopy was used to provide an estimate of the saturation concentration of water in soybean oil. By following the time evolution of the infrared absorption spectrum of water-oil mixtures, the saturation of water in soybean oil was found to reach equilibrium after 1 h. From the absorption spectra of neat water and neat soybean oil and the application of the Beer-Lambert law to an estimation of the absorption of a mixture from its individual components, it was estimated that the saturation concentration of water is 0.010 M. This estimate was supported by molecular modeling using the latest semiempirical methods (in particular, GFN2-xTB). While for most applications the very low solubility has little impact, the implications in those exceptions were discussed.

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.

A common perception exists that glycerol provides an inert-like environment modifying viscosity and index of refraction by its various concentrations in aqueous solution. Said perception is herein challenged by investigating the effects of the glycerol environment on the spectroscopic properties of fluorescein, as a representative fluorophore, using steady-state and time-resolved techniques and computational chemistry. Results strongly suggest that the fluorescence quantum yield, measured fluorescence lifetime (FLT), natural lifetime and calculated fluorescence lifetime are all highly sensitive to the presence of glycerol. Glycerol was found to impact both the ground and first excited states of fluorescein, quenching and modifying both absorption and emission spectra, affecting the fundamental electrical dipoles of the ground and first excited singlet states, and lowering FLT and quantum yield. Furthermore, the SternVolmer, LippertMataga, Perrin and StricklerBerg relations indicate that glycerol acts upon fluorescein in aqueous solution as a quencher and alters the fluorescein geometry. Predictions made by computational chemistry impressively correspond to experimental results, both indicating changes in the properties of fluorescein at around 35% v/v aqueous glycerol, a clear indication that glycerol is not an innocent medium. This study proposes the StricklerBerg relation as a means of detecting non-negligible effects of a hosting medium on its host fluorophore. These new insights on the molecular structures, the interactions between glycerol and its host fluorophore, and the effects of one on the other may be essential for understanding fundamental phenomena in chemistry and related fields. Graphic abstract: [Figure not available: see fulltext.]

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.

Microbial production and consumption of methane are widespread in natural and artificial environments, with important economic and climatic implications. Attempts to use the isotopic composition of methane to identify its sources are complicated by incomplete understanding of the mechanisms of variation in methane's isotopic composition. Knowledge of the equilibrium isotope fractionations among the large organic intracellular intermediates in the microbial pathways of methane production and consumption must form the basis of any exploration of the mechanisms of isotopic variation, but estimates of these equilibrium isotope fractionations are currently unavailable. To address this gap, we calculated the equilibrium isotopic fractionation of carbon (¹³C/¹²C) and hydrogen (D/H) isotopes among compounds in the anaerobic methane metabolisms, as well as the abundance of double isotope substitutions (\u201cclumping,\u201d i.e., a single ¹³CD bond or two ¹²CD bonds) in these compounds. The isotope fractionation factors were calculated using density functional theory at the M06-L/def2-TZVP level of theory with the SMD implicit solvation model, which we recently tested against measured equilibrium isotope fractionations. The computed ¹³β and ²β values decrease with decreasing oxidation state of the carbon atom in the molecules, resulting in a preference for enrichment in ¹³C and D in the molecules with more oxidized carbon. Using the computed β values, we calculated the equilibrium isotope fractionation factors in the prominent methanogenesis pathways (hydrogenotrophic, methylotrophic and acetoclastic) and in the pathway for anaerobic oxidation of methane (AOM) over a temperature range of 0700 °C. Our calculated equilibrium fractionation factors compare favorably with experimental constraints, where available, and were then used to investigate the relation between the apparent isotope fractionation during methanogenesis or AOM and the thermodynamic drive for these reactions. We show that a detailed map of the equilibrium fractionation factors along these metabolic pathways allows for an evaluation of the contribution of equilibrium and kinetic isotope effects to apparent isotope fractionations observed in laboratory, natural and artificial settings. The comprehensive set of equilibrium isotope fractionation factors calculated in this study provides a firm basis for future explorations of isotope effects in methane metabolism.

In the past the formyloxyl radical, HC(O)O, had only been rarely experimentally observed, and those studies were theoretical-spectroscopic in the context of electronic structure. The absence of a convenient method for the preparation of the formyloxyl radical has precluded investigations into its reactivity towards organic substrates. Very recently, we discovered that HC(O)O is formed in the anodic electrochemical oxidation of formic acid/lithium formate. Using a [CoIIIW12O40]5- polyanion catalyst, this led to the formation of phenyl formate from benzene. Here, we present our studies into the reactivity of electrochemically in situ generated HC(O)O with organic substrates. Reactions with benzene and a selection of substituted derivatives showed that HC(O)O is mildly electrophilic according to both experimentally and computationally derived Hammett linear free energy relationships. The reactions of HC(O)O with terminal alkenes significantly favor anti-Markovnikov oxidations yielding the corresponding aldehyde as the major product as well as further oxidation products. Analysis of plausible reaction pathways using 1-hexene as a representative substrate favored the likelihood of hydrogen abstraction from the allylic C-H bond forming a hexallyl radical followed by strongly preferred further attack of a second HC(O)O radical at the C1 position. Further oxidation products are surmised to be mostly a result of two consecutive addition reactions of HC(O)O to the CC double bond. An outer-sphere electron transfer between the formyloxyl radical donor and the [CoIIIW12O40]5- polyanion acceptor forming a donor-acceptor [D+-A-] complex is proposed to induce the observed anti-Markovnikov selectivity. Finally, the overall reactivity of HC(O)O towards hydrogen abstraction was evaluated using additional substrates. Alkanes were only slightly reactive, while the reactions of alkylarenes showed that aromatic substitution on the ring competes with C-H bond activation at the benzylic position. C-H bonds with bond dissociation energies (BDE) ≤ 85 kcal mol-1 are easily attacked by HC(O)O and reactivity appears to be significant for C-H bonds with a BDE of up to 90 kcal mol-1. In summary, this research identifies the reactivity of HC(O)O towards radical electrophilic substitution of arenes, anti-Markovnikov type oxidation of terminal alkenes, and indirectly defines the activity of HC(O)O towards C-H bond activation.

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.

We report the hydrogenation of carbamates and urea derivatives, two of the most challenging carbonyl compounds to be hydrogenated, catalyzed for the first time by a complex of an earth-abundant metal. The hydrogenation reaction of these CO2-derived compounds, catalyzed by a manganese pincer complex, yields methanol in addition to amine and alcohol, which makes this methodology a sustainable alternative route for the conversion of CO2 to methanol, involving a base-metal catalyst. Moreover, the hydrogenation proceeds under mild pressure (20 bar). Our observations support a hydrogenation mechanism involving the Mn-H complex. A plausible catalytic cycle is proposed based on informative mechanistic experiments.

The application of stable isotopes to address a wide range of biochemical, microbiological and environmental problems is hindered by the experimental difficulty and the computational cost of determining equilibrium isotopic fractionations (EIF) of large organic molecules. Here, we evaluate the factors that impact the accuracy of computed EIFs and develop a framework for cost-effective and accurate computation of EIFs by density functional theory (DFT). We generated two benchmark databases of experimentally determined EIFs, one for H isotopes and another for the isotopes of the heavy atoms C, N and O. The accuracy of several DFT exchange-correlation functionals in calculating EIFs was then evaluated by comparing the computational results to these experimental datasets. We find that with the def2-TZVP basis set, O3LYP had the lowest mean absolute deviation (21 parts per thousand and 3.9 parts per thousand for the isotopic fractionation of H and the heavier atoms, respectively), but the GGA/meta-GGA functionals tau HCTHD3BJ, tau HCTH and HCTH have similar performances (22 parts per thousand and 4.1 parts per thousand, respectively, for tau HCTHD3BJ). Leveraging the good performance of computationally efficient functionals, we provide a robust, practical, experimentally validated framework for using DFT to accurately predict EIFs of large organic molecules, including uncertainty estimates.

The accumulated knowledge regarding molecular architectures is based on established, reliable, and accessible analytical tools that provide robust structural and functional information on assemblies. However, both the dynamicity and low population of noncovalently interacting moieties within studied molecular systems limit the efficiency and accuracy of traditional methods. Herein, the use of a saturation transfer-based NMR approach to study the dynamic binding characteristics of an anion to a series of synthetic receptors derived from bambusuril macrocycles is demonstrated. The exchange rates of BF4- are mediated by the side chains on the receptor (100 s(-1)

A new database of transition metal reaction barrier heights (MOBH35) is presented. Benchmark energies (forward and reverse barriers and reaction energy) are calculated using DLPNO-CCSD(T) extrapolated to the complete basis set limit using a Weizmann-1-like scheme. Using these benchmark energies, the performance of a wide selection of density functional theory (DFT) exchange-correlation functionals, including the latest from the Martin, Truhlar, and Head-Gordon groups, is evaluated. It was found, using the def2-TZVPP basis set, that the omega B97M-V (MAD 1.7 kcal/mol), omega B97M-D3BJ (MAD 1.9 kcal/mol), omega B97X-V (MAD 2.0 kcal/mol), and revTPSSO-D4 (MAD 2.2 kcal/mol) hybrid functionals are recommended. The double-hybrid functionals B2K-PLYP (MAD 1.7 kcal/mol) and revDOD-PBEP86D4 (MAD 1.8 kcal/mol) also performed well, but this has to be balanced by their increased computational cost.

We report on the fabrication and characterization of organic phototransistors (OPTs) based on fluorescent nanocrystals assembLed from a simple organic dye molecule (N,N' -bis(2,4-dimethylpent-3-yl)perylene-3,4:9,10-tetracarboxylic diimide, DMP-PDI). The OPT active Layer is based on DMP-PDI nanocrystals assembLed in aqueous solution or within polymer films. Despite the absence of any pi-overlap, the nanocrystals show mobilities as high as (5 +/- 1) x 10(-3) cm(2) V-1 s(-1) in polymer films, which is due to imide/ pi-core noncovalent interactions Leading to substantial electronic coupling as revealed by computational studies. The OPTs strongly respond to white Light irradiation, resulting in a decrease in threshoLd voltage by as much as 40 V. OPTs based on nanocrystals assembLed within poLymer fiLms have threshoLd voltages dose to 0 V upon illumination and a high photo/dark current ratio (P = 4 x 10(3)). We show that the organic crystals Lacking pi-overlap mediate charge mobility and are advantageous as active Layers for OPTs due to diminished nonradiative decay.

The present study investigates the fluorescence properties of BO21 and their dependence on various intracellular conditions. The results obtained with cell-free solutions indicate that the influences of pH and temperature on the fluorescence spectra are negligible, while viscosity, various proteins and heparin have significant influence. In the presence of heparin, a red shift of the emission spectrum (from 515 to 550 nm) is observed, suggesting that this shift cannot simply be attributed to electrostatic interaction between BO21 and the polyanionic heparin, but rather to aggregation of BO21 on the polyanion. In water, the quantum yield of BO21 was found to be 1000 times lower than that of fluorescein, yet surprisingly its fluorescence polarization (FP) was found to be about 40 times higher (FP = 0.470), even though both have similar structures and molecular weights. A thorough analytical and experimental investigation of these phenomena indicates that the very high FP of BO21 in water is a consequence of its very short lifetime. However, upon the addition of heparin to aqueous BO21, the fluorescence lifetime (FLT) of BO21 increases from tau = 10.35 to 56.5 ps, with a consequent dramatic drop in its fluorescence polarization from 0.470 to 0.230. From its behavior in aqueous glycerol solution, it is hypothesized, with support from theoretical calculations, that BO21 is a molecular rotor. Using these properties, BO21 may be a good candidate as a sensor, for example, of heparin levels in blood or of intracellular viscosity.

Isomerization and carbon chemistry in the gas phase are key processes in many scientific studies. Here we report on the isomerization process from linear $${{\rm C}}-{10}^ -$$ C 10 - to its monocyclic isomer. $${{\rm C}}-{10}^ -$$ C 10 - ions were trapped in an electrostatic ion beam trap and then excited with a laser pulse of precise energy. The neutral products formed upon photoexcitation were measured as a function of time after the laser pulse. It was found using a statistical model that, although the system is excited above its isomerization barrier energy, the actual isomerization from linear to monocyclic conformation takes place on a very long time scale of up to hundreds of microseconds. This finding may indicate a general phenomenon that can affect the interstellar medium chemistry of large molecule formation as well as other gas phase processes.

Organic crystalline materials are used as dyes/pigments, pharmaceuticals, and active components of photonic and electronic devices. There is great interest in integrating organic crystals with inorganic and carbon nanomaterials to create nanocomposites with enhanced properties. Such efforts are hampered by the difficulties in interfacing organic crystals with dissimilar materials. Here, an approach that employs organic nanocrystallization is presented to fabricate solution-processed organic nanocrystal/carbon nanotube (ONC/CNT) hybrid materials based on readily available organic dyes (perylene diimides (PDIs)) and carbon nanotubes. The hybrids are prepared by self-assembly in aqueous media to afford free-standing films with tunable CNT content. These exhibit excellent conductivities (as high as 5.78 ± 0.56 S m⁻¹), and high thermal stability that are superior to common polymer/CNT hybrids. The color of the hybrids can be tuned by adding various PDI derivatives. ONC/CNT hybrids represent a novel class of nanocomposites, applicable as optoelectronic and conductive colorant materials.

Identifying the mechanism of a catalytic reaction is paramount for designing new and improved catalysts. Several alternative catalytic cycles for the copper/2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)-catalyzed aerobic oxidation of alcohols to the corresponding aldehydes or ketones were examined using DFT at the SMD(CH3CN)-RIJCOSX-DSDPBEB95/def2-TZVP//DF-PBED3BJ/def2-SVP level of theory. A catalytic cycle in which TEMPO remains coordinated to copper throughout was identified as the most likely mecha-nism. There are three components to the catalytic cycle: 1) hydrogen transfer from the alkoxyl ligand to coordinated TEMPO, 2) oxygen activation with formation of a peroxo complex, and 3) alcohol activation with transfer of the OH proton to the peroxo ligand. The oxidation takes place via a six-membered intramolecular hydrogen-transfer transition state. Importantly, this is not the rate-determining step, which instead involves oxygen activation and/or the initial alcohol activation.

Enolonium species/iodo(III) enolates of carbonyl compounds have been suggested to be intermediates in a wide variety of hypervalent iodine induced chemical transformations of ketones, including alpha-C-O, alpha-C-N, alpha-C-C, and alpha-carbon- halide bond formation, but they have never been characterized. We report that these elusive umpoled enolates may be made as discrete species that are stable for several minutes at-78 degrees C, and report the first spectroscopic identification of such species. It is shown that enolonium species are direct intermediates in C-O, C-N, C-Cl, and C-C bond forming reactions. Our results open up chemical space for designing a variety of new transformations. We showcase the ability of enolonium species to react with prenyl, crotyl, cinnamyl, and allyl silanes with absolute regioselectivity in up to 92% yield.

The various factors influencing the accuracy of C-13 NMR calculations using density functional theory (DFT), including the basis set, exchange-correlation (XC) functional, and isotropic shielding calculation method, are evaluated. A wide selection of XC functionals (over 70) were considered, and it was found that long-range corrected functionals offer a significant improvement over the other classes of functionals. Based on a thorough study, it is recommended that for calculating NMR chemical shifts (5) one should use the CSGT method, the COSMO solvation model, and the LC-TPSSTPSS exchange-correlation functional in conjunction with the cc-pVTZ basis set. A selection of problems in natural product identification are considered in light of the newly recommended level of theory.

The characteristics of host-guest systems, such as molecular recognition, complexation, encapsulation, guest composition, and dynamic exchange, are manifested by changes in the chemical shifts (Δω) in the NMR spectrum. However, in cases where NMR signals cannot be detected, due to low concentrations, poor solubility, or relatively fast exchange, an alternative is needed. Here, we show that by using the magnetization transfer (MT) method, the undetectable NMR signals of host-guest assemblies can be amplified by two orders of magnitude. It is shown that the binding kinetics characteristics of a fluorinated guest and cucurbit[n]uril (CB[n]) hosts in aqueous solutions determine the NMR signal amplification of host-guest assemblies. In addition, by using the MT technique within the ¹⁹F-NMR framework, one can detect μM concentrations of the complex and study the effect of different solutes on the resulting host-guest system. The results expand the \u201cNMR toolbox\u201d available to explore a wider range of dynamic host-guest systems in which NMR signals cannot be detected.

By providing accurate distance measurements between spin labels site-specifically attached to bio-macromolecules, double electron-electron resonance (DEER) spectroscopy provides a unique tool to probe the structural and conformational changes in these molecules. Gd³⁺-tags present an important family of spin-labels for such purposes, as they feature high chemical stability and high sensitivity in high-field DEER measurements. The high sensitivity of the Gd³⁺ ion is associated with its high spin (S = 7/2) and small zero field splitting (ZFS), resulting in a narrow spectral width of its central transition at high fields. However, under the conditions of short distances and exceptionally small ZFS, the weak coupling approximation, which is essential for straightforward DEER data analysis, becomes invalid and the pseudo-secular terms of the dipolar Hamiltonian can no longer be ignored. This work further explores the effects of pseudo-secular terms on Gd³⁺-Gd³⁺ DEER measurements using a specifically designed ruler molecule; a rigid bis-Gd³⁺-DOTA model compound with an expected Gd³⁺-Gd³⁺ distance of 2.35 nm and a very narrow central transition at the W-band (95 GHz). We show that the DEER dipolar modulations are damped under the standard W-band DEER measurement conditions with a frequency separation, Δν, of 100 MHz between the pump and observe pulses. Consequently, the DEER spectrum deviates considerably from the expected Pake pattern. We show that the Pake pattern and the associated dipolar modulations can be restored with the aid of a dual mode cavity by increasing Δν from 100 MHz to 1.09 GHz, allowing for a straightforward measurement of a Gd³⁺-Gd³⁺ distance of 2.35 nm. The increase in Δν increases the contribution of the -5/2〉 → -3/2〉 and -7/2〉 → -5/2〉 transitions to the signal at the expense of the -3/2 〉 → -1/2〉 transition, thus minimizing the effect of dipolar pseudo-secular terms and restoring the validity of the weak coupling approximation. We apply this approach to the A93C/N140C mutant of T4 lysozyme labeled with two different Gd³⁺ tags that have narrow central transitions and show that even for a distance of 4 nm there is still a significant (about two-fold) broadening that is removed by increasing Δν to 636 MHz and 898 MHz.

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.

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 η²-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 η²-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 η²-coordination complexes. The product distribution can be controlled by the concentration of the reactants and/or the presence of excess phosphine.

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.

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.

A series of iron dicarbonyl complexes with bipyridine-based PNN pincer ligands were synthesized and characterized by multinuclear NMR spectroscopy (¹H, ¹³C, ¹⁵N, ³¹P), IR spectroscopy, cyclic voltammetry, ⁵⁷Fe Mössbauer spectroscopy, XPS spectroscopy, and single-crystal X-ray diffraction. The complexes with the general formula [(R-PNN)Fe(CO)₂] (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)₂] (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 ^.-), suggests that the complexes can be described as Fe^I 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 ⁰ 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.

The electronic structures of a number of iron, cobalt, vanadium, and titanium complexes with the 2,2-bipyridine (bpy) ligand were considered using the multireference CASSCF and NEVPT2 methods. Many of these systems have been studied in the past using B3LYP and were then found to contain the bpy ligand as a radical anion. For many of the cases, this is contradicted by our multireference calculations. While there are instances where the ligand is indeed a radical anion, in many cases it remains neutral and is involved in backbonding from the metal center. For those cases where CASSCF is too costly, a number of DFT functionals, including the newer double-hybrid functionals, were evaluated against the CASSCF data. It was found that nonhybrid functionals, especially those containing the kinetic energy density τ, were the best at predicting the electronic nature of the complexes. The τ-HCTH and HCTH functionals were the top performers, correctly predicting eleven out of eleven test cases and with the lowest mean unsigned errors (MUE, 7.6 and 7.8 kcal·mol^-1, respectively); the M06-L, N12, BLYP, PBE, and TPSS functionals also did well, while B3LYP had significant problems.

The synthesis and characterization of new iron pincer complexes bearing bipyridine-based PNN ligands is reported. Three phosphine-substituted pincer ligands, namely, the known ^tBu-PNN (6-((di-tert-butylphosphino) methyl)-2,2-bipyridine) and the two new ⁱPr-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)₂] and bis-chelated dicationic complexes of the type [(R-PNN)₂Fe]²⁺. The complexes [(R-PNN)Fe(X)₂] (1: R = ^tBu, X = Cl, 2: R = ^tBu, X = Br, 3: R = ⁱPr, X = Cl, and 4: R = ⁱPr, X = Br) are readily prepared from reactions of FeX₂ 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 ⁱPr-PNN, diamagnetic hexacoordinated dicationic complexes of the type [( ⁱPr-PNN)₂Fe](X)₂ (5: X = Cl, and 6: X = Br) are formed. The reactions of Ph-PNN with FeX₂ in a 1:1 ratio lead to similar complexes of the type [(Ph-PNN)₂Fe](FeX₄) (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^II 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*)₂Fe] (9: R = ⁱPr, and 10: R = Ph) were synthesized by reactions of the dicationic complexes 6 and 8 with KO ^tBu. 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.

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^R type ligands (PNP = 2,6- bis[(dialkylphosphino)methyl]pyridine with R = ⁱPr, ^tBu), which can be readily transformed into the doubly deprotonated anionic species. The complexes [Ni(PNP^R)Cl]Cl (3, R = ⁱPr; 4, R = ^tBu) are readily prepared from the reaction of NiCl ₂·6H₂O and the PNP^R 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^R*)Me] (7, R = ⁱPr; 8, R = ^tBu), 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)₃][Ni(PNP^iPr**)Me] (9-DME, DME = 1,2-dimethoxyethane) and [Li(Et₂O)₂] [Ni(PNP^tBu**)(Me)] (10-Et₂O), 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 ₂ and tautomerization gives [Li][Ni(PNP^iPr*-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.

The dearomatized complex cis-[Re(PNP^tBu*)(CO)₂] (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 ₃-benzonitrile from cis-[Re(PNP^tBu-N=CPh ^pCF3)(CO)₂] (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 ^tBu-HNC=CHPh)(CO)₂] (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^tBu-HN=CC(Me)Ph)(CO)₂]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.

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( ^tBu₂PCH₂)pyridine) with RuCl ₃(NO)(PPh₃)₂ yielded the Ru(II) complex 3. Chloride displacement by BAr^F- (BAr^F- = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) gave the crystallographicaly characterized, linear NO Ru(II) complex 4, which upon treatment with NaBEt ₃H yielded the Ru(0) complexes 5. The crystallographically characterized Ru(0) square planar complex 5·BF₄ bears a linear NO ligand located trans to the pyridilic nitrogen. Further treatment of 5·BF₄ 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-(^tBu ₂PCH₂)-6-(Et₂NCH₂)pyridine) with RuCl₃(NO)(H₂O)₂ 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 RuCl₃(NO)(H₂O)₂ and Et₃N in ethanol. Reaction of the "long arm" PN²N ligand (PN ²N = 2-(^tBu₂PCH₂-)-6-(Et ₂NCH₂CH₂)pyridine) with RuCl ₃(NO)(H₂O)₂ 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 PN²N with RuCl ₃(NO)(H₂O)₂ 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.

A combinatorial fluorescent molecular sensor operates as a highly efficient molecular security system. The ability of a pattern-generating molecule to process diverse sets of chemical inputs, discriminate among their concentrations, and form multivalent and kinetically stable complexes is demonstrated as a powerful tool for processing a wide range of chemical "passwords" of different lengths. This system thus indicates the potential for obtaining unbreakable combination locks at the molecular scale.

We present a mechanistic study demonstrating selective Ar_f-Cl bond activation preceded by η² coordination of Pd(PEt ₃)₂ to a C=C moiety of a partially fluorinated substrate. An intramolecular ring-walking process to activate the Ar_f-Cl bond is plausible, but an intermolecular reaction becomes dominant in the presence of PEt₃. The latter pathway is significantly enhanced, since PEt ₃ promotes dissociation of Pd(PEt₃)₃ from the C=C moiety followed by activation of the Ar_f-Cl bond. Our observations also show that PEt₃ 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_v2/SDD(d) level of theory).

Trifluoroethanol was oxidized with O₂ to trifluoroethyl trifluoracetate (>98% selectivity) using Pt^II(dppz)Cl₂ as a catalyst in the presence of H₂SO₄; Pt^II(phen)Cl₂ was inactive. Kinetic isotope effects suggest the CH bond activation as the rate determining step and DFT calculations showed different frontier orbitals for Pt^II(dppz) and Pt^II(phen)-based catalysts.

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).

Working together to uncover the truth: A molecule-sized diagnostic system combining several recognition elements and four fluorescence-emission channels enabled the identification of a wide range of pharmaceuticals on the basis of distinct photophysical processes. The molecular sensor (see simplified representation; ID=identification) was also used to analyze drug concentrations and combinations in urine samples in a high-throughput manner.

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 _F-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.

The new, structurally characterized hydrido carbonyl tetrahydridoborate iron pincer complex [(iPr-PNP)Fe(H)(CO)(η¹-BH ₄)] (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 BH₃ scavenger) resulted in a mixture of trans-[(iPr-PNP)Fe(H)₂(CO)] (4a) and cis-[(iPr-PNP)Fe(H) ₂(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 Fe⁰ 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.

Unlike N-heterocyclic carbenes (NHCs), which are now used ubiquitously in metal-based chemistry, the nitrogen-derived analogue (in which a carbon is replaced with the isoelectronic nitrogen cation, a nitrenium ion) has remained elusive as a ligand for metals. This is especially intriguing, because several other main-group analogues of NHCs have been prepared, and have been shown to coordinate with transition-metal complexes. Here, we describe the preparation of several N-heterocyclic nitrenium ions that are isoelectronic and isostructural to NHCs, and study their ligand properties. The formation of relatively strong nitrenium-metal bonds is unambiguously confirmed, in solution by selective ¹⁵ N-labelling experiments, and in the solid state by X-ray crystallography. Experimental and computational studies of the electronic properties of this novel type of ligand suggest that they are poor σ-donors and good μ-acceptors.

The anionic dearomatized complex [(PNP*)Rh^ICl]K (2; PNP = 2,6-bis((di-tert-butylphosphino)methyl)pyridine, PNP* = deprotonated PNP) was prepared by reaction of the aromatic (PNP)Rh^ICl complex 1 with KN(SiMe₃)₂ in dry benzene. Spectroscopic characterization and DFT calculations confirm a nonaromatic square-planar structure of complex 2. Under an atmosphere of dry argon, 2 undergoes facile C-H activation of benzene by cooperation between the metal center and the pincer ligand, with aromatization of the ligand, to form the complex (PNP)Rh^I(C ₆H₅) (3a). This reaction is inhibited by dinitrogen, which reacts with 2 to form the complex (PNP*)Rh^I(N₂) (4), indicating higher stabilization of the 14-electron (PNP*)Rh ^I species 5 by dinitrogen as compared with chloride. Similarly, treatment of 2 with CO results in KCl liberation to form the dearomatized (PNP*)Rh^ICO (8). In a protic environment, the dearomatized complex 2 is quickly reprotonated to regenerate the aromatic starting complex 1. Upon treatment with MeI, 2 undergoes oxidative addition to form the nonaromatic (PNP*)Rh^III(CH₃)Cl (10), while the dearomatized ligand remains intact. Complex 2 undergoes facile activation of H₂ to form the monohydride (PNP)Rh^I(H) (11a) and with D₂ to form (PNP)Rh^I(D) (11b) with benzylic-D incorporation, via metal-ligand cooperation by aromatization of the ligand. The reactivity of 2 with H₂ is significantly higher than that of 4.

Elucidation of photoinduced charge transfer behavior in organic dye/metal hybrids is important for developing photocatalytic systems for solar energy conversion. We report the synthesis and photophysical characterization of a perylene-3,4:9,10-bis(dicarboximide) (PDI)-ruthenium(II) complex, bis-PDI-2,2-bipyridineRu(II)Cl₂(CN^tbutyl) ₂, which has favorable energetics, ΔG_CS ≈ -1.0 eV, for singlet electron transfer from the Ru complex to PDI. Time-resolved optical spectroscopy reveals that upon selective photoexcitation of PDI, ultrafast charge transfer (

Multicomponent self-propagating molecular assemblies (SPMAs) have been generated from an organic chromo-phore, a redox-active polypyridyl complex, and PdCl₂. The structure of the multicomponent SPMA is not a linear combination of two assemblies generated with a single molecular constituent. Surface-confined assemblies formed from only the organic chromophore and PdCl₂ are known to follow linear growth, whereas the combination of polypyridyl complexes and PdCl₂ results in exponential growth. The present study demonstrates that an iterative deposition of both molecular building blocks with PdCl₂ results in an exponentially growing assembly. The nature of the assembly mechanism is dictated by the polypyridyl complex and overrides the linear growth process of the organic component. Relatively smooth, multicomponent SPMAs have been obtained with a thickness of ∼20 nm on silicon, glass, and indium-tin oxide (ITO) coated glass. Detailed information of the structure and of the surface-assembly chemistry were obtained using transmission optical (UV/Vis) spectroscopy, ellipsometry, atomic force microscopy (AFM), synchrotron X-ray reflectivity (XRR), and electrochemistry.

It was recently reported (Shirman, J. Phys. Chem. B, 2008, 112, 8855) that the stable dianion of perylene diimide can be prepared in water. Herein, a computational study (using DFT at the M06-2X/6-31++G* level of theory) of this species is presented. It is shown that this dianion is aromatic and that its reaction with water is highly endergonic. The primary cause for this is the stabilization provided by the enhanced aromaticity of the dianion relative to its neutral counterpart. Comparison with other aromatic dianions is also presented.

The complex (PNP)Ir^I(CH₂COCH₃) 2 (PNP = 2,6-bis((di-tert-butylphosphino)methyl)pyridine) was prepared by reaction of the dearomatized, electron-rich complex (PNP)Ir^I(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^I(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 H₂ (D₂) indicates an equilibrium between complex 2 and the nonaromatic (PNP)Ir^III(H) (CH₂COCH₃) complex 2b, which is the species that actually activates H₂ to exclusively form the trans-dihydride (PNP)Ir ^III(H)₂(CH₂COCH₃) (5a) and activates D₂ 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 ^I(C₆H₅) (6a) and elimination of acetone. DFT studies show that the benzene C-H bond is actually activated by the dearomatized "bare" (PNP)Ir^I intermediate 2c, formed upon acetone elimination from 2.

The electrochemical properties of a metallosupramolecular network that undergoes reversible redox chemistry on indium-tin oxide (ITO)-coated glass substrates have been investigated. The redox-active osmium complexes are electrochemically accessible even for films with a thickness > 15 nm. The electrochemical data correlates well with our previously observed self-propagating growth process, for which the electron density for the assemblies remains constant during film growth. Electron-transfer rate constants obtained by potential step chronoamperometry experiments suggest an exceptionally low attenuation factor, β, of 0.013 ± 0.001 Å^-1. However, the intrinsically porous nature of the assembly could be to a large extent or even entirely responsible for such a low value.

The pincer-type complexes [(PCN)PtR] [R = H, 2; Me, 4; PCN = C ₆H₄[CH₂P(tBu)₂](CH₂) ₂N(CH₃)₂} react with MeLi or Et ₃BHNa, to give anionic cis-Pt(Me).H complexes [(PCN*)Pt(H)(Me) J-Li+(Me irons to P; PCN* denotes the PCN ligand in which the amine arm is not coordinated) and [(PCN*)Pt(Me)(H)]-Na+ (H trans to P). Only the isomer in which the incoming nucleophile is situated trans to the phosphane ligand is formed. These first d⁸ anionic alkyl hydride complexes were fully characterized spectroscopically, The hemilabile PCN ligand allows for reversible de-coordination of the amine arm, thereby providing a desirable balance of stability vs. reactivity. Theoretical calculations on model systems indicate a concerted mechanism in which the nucleophilic attack and the amine dissociation occur concurrently. The (unobserved) methane reductive elimination from the stable anionic methyl hydride complex [(PCN*)Pt(Me)(H)]-Li+ (3) is thermodynamically and kinetically unfavorable, as indicated by DFT. This complex reacts with electrophiles, such, as water and methyl iodide, to yield exclusively methane and the corresponding organometallic product (either 2 or 4). This reactivity was also further examined by DFT.

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 ₃ as well as density functional theory calculations were used to shed light on the N-H activation mechanism.

Metal-organic networks (MONs) were created by a stepwise solution deposition approach from vinylpyridine-based building blocks and PdCl ₂. 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.

"Figure Presented" Stolen identity: The molecular geometries of a series of cross-linkers that bear between one and four pyridyl moieties are expressed in the optical properties of AuNP assemblies (see picture). TEM analysis indicates that the molecular-level structural differences of the cross-linkers are also transferred at the submicrometer level in the formation of the AuNP assemblies.

Signal amplification has been demonstrated with surface-bound electrochromic complexes that can exist in one of two oxidation states (M ^2+/3+). Reaction of FeCl₃ with covalently immobilized Os²⁺ complexes on glass substrates converts the metal centers from one oxidation state to the other. The formed Fe²⁺ reduces a series of Ru³+-based monolayers. The absorption of light is coupled with the oxidation state of the complexes and provides the output for the monolayer-based device. The gain of the setup can be controlled by the addition of a Fe ²⁺ chelating ligand.

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 ₂/KOH results in H₂ 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.

A ruthenium(II) bipyridine complex with proximal phenylselenium tethers, [Ru](H₂O)₂, reacted intramolecularly with O₂ 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)₂, 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 ¹H NMR with the associated Curie plot that showed that [Ru](O)₂ 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)₂ is a potent oxygen transfer species of both O₂-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 PPh₃:O₂ = ̃2 in a catalytic oxidation of PPh₃ suggests a dioxygenase type activation of O ₂ with structural identification of the O-O bond cleavage reaction step, formation of [Ru](O)₂ as an intermediate, and the proof that [Ru](O)₂ is a donor of both oxygen atoms.

(Figure Presented) Designer materials: HOMO-LUMO engineering of coordination-based oligomers covalently bound to silicon or glass has been achieved by the use of a partially fluorinated chromophore (see graphic). The experimental and computationally derived physical chemical properties of these assemblies are compared to their non-fluorinated analogues.

A series of cationic, neutral, and anionic Pd^II and Pt ^II 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(SiMe₃)₂ or ^tBuOK), while the anionic complexes [(PNP*)MX] ^-Y⁺ (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(SiMe₃)₂ 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]^-Li⁺. 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.

The extension of molecular mechanics to reactive systems, metals, and covalently bonded clusters with variable coordination numbers requires new functional forms beyond those popular for organic chemistry and biomolecules. Here we present a new scheme for reactive molecular mechanics, which is denoted as the valence-bond order model, for approximating reactive potential energy surfaces in large molecules, clusters, nanoparticles, solids, and other condensed-phase materials, especially those containing metals. The model is motivated by a moment approximation to tight binding molecular orbital theory, and we test how well one can approximate potential energy surfaces with a very simple functional form involving only interatomic distances with no explicit dependence on bond angles or dihedral angles. For large systems the computational requirements scale linearly with system size, and no diagonalizations or iterations are required; thus the method is well suited to large-scale simulations. The method is illustrated here by developing a force field for particles and solids composed of aluminum and hydrogen. The parameters were optimized against both interaction energies and relative interaction energies. The method performs well for pure aluminum clusters, nanoparticles, and bulk lattices and reasonably well for pure hydrogen clusters; the mean unsigned error per atom for the aluminum-hydrogen clusters is 0.1 eV/atom.

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 ¹⁹F, ³¹P, and ¹⁹⁵Pt nuclei communicate over large distances (0.9-1.3 nm) through bond rather than through space. Spin-spin couplings between ¹⁹⁵Pt and ¹⁹F over seven bonds and between ³¹P and ¹⁹F over eight bonds are observed with ⁷J_PtF = 2.9 Hz and ⁸J_PF = 11.8 Hz. Remarkably, a very large spin coupling between ¹⁹⁵Pt and ¹⁹F over six bonds (⁶J _PtF = 40.1 Hz) is also observed in a structurally related pyridinium complex. Experimental and gNMR (version 5.0) simulated ¹⁹F{ ¹H}, ³¹P{¹H}, and ¹⁹⁵Pt{ ¹H} spectra of the complexes reveal a three-spin AMY system (A = ³¹P, M = ³¹P, Y = ¹⁹F) or a five-spin AMY3 flanked by a four-spin AMXY or a six-spin AMXY3 system (X = ¹⁹⁵Pt), 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.

DFT calculations on the hydrogenation of a (PNP)Ir(i) complex, to give the trans - rather then the cis - dihydride isomer, show that the reaction proceeds via a deprotonation/protonation of the ligand arm with concomitant dearomatization/aromatization of the pyridine core. Thus, the actual H ₂ activation step occurs by an Ir(iii) complex and not by the Ir(i) starting complex, as supported by experimental observations. This ligand participation allows for products that would otherwise be inaccessible. In addition, trace amounts of water, which are likely to be present in the solvent, facilitate proton transfer reaction steps.

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 ₂ ¹⁷O and H₂ ¹⁸O show unequivocally that the process of oxygen-oxygen bond formation is intramolecular, establishing a previously elusive fundamental step toward dioxygen-generating homogeneous catalysis.

Assemblies with molecular-level organization based on organic chromophores and a bimetallic palladium complex are presented. A layer-by-layer strategy is employed by alternately coordinating vinylpyridine-terminated chromophores to the metal centers to form cationic oligomers. These new structures are formed from solution on quartz and silicon substrates functionalized with a covalently bound template layer. Twelve consecutive deposition steps result in structurally regular assemblies as demonstrated by linear increases in the ellipsometrically determined thickness and UV-vis optical absorption. The increase in thickness for each additional layer shows that the long-range order of the system is determined by the structure of the chromophores and by the square-planar geometry of the metal centers. Furthermore, the optical properties indicate that the conjugation length of the assembly component does not increase in the surface-bound oligomers with each additional deposition cycle. Structural communication is transferred via the system components, but they remain electronically isolated. This is supported by density functional theory (DFT) calculations.

We present a new electronic structure approximation called Tight Binding Configuration Interaction. It uses a tight-binding Mamiltonian to obtain orbitais that are used in a configuration interaction calculation that includes explicit charge interactions. This new method is better capable of predicting energies, ionization potentials, and fragmentation charges than the Wolfsberg-Helmholz Tight-Binding and Many-Body Tight-Binding models reported earlier (Staszewska, G.; Staszewski, P.; Schultz, N. E.; Truhlar, D. Phys. Rev. 6 2005, 71, 045423). The method is illustrated for clusters and nanoparticles containing aluminum.

Perylene diimide (PDI) bearing polyethylene glycol substituents at the imide positions was reduced in water with sodium dithionite to produce an aromatic dianion. The latter is stable for months in deoxygenated aqueous solutions, in contrast to all known aromatic dianions which readily react with water. Such stability is due to extensive electron derealization and the aromatic character of the dianion, as evidenced by spectroscopic and theoretical studies. The dianion reacts with oxygen to restore the parent neutral compound, which can be reduced again in an inert atmosphere with sodium dithionite to give the dianion. Such reversible charging renders PDIs useful for controlled electron storage and release in aqueous media. Simple preparation of the dianion, reversible charging, high photoredox power, and stability in water can lead to development of new photofunctional and electron transfer systems in the aqueous phase.

The Rh^III complex [(PNP)Rh(CN)(CH₃)][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(CNCH₃)][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.

Both experimental and theoretical evidence suggest that the proton exchange between water and the methyl group in [TpPt(CO)CH₃] (1, Tp = hydridotripyrazolylborate) involves the formation and deprotonation of a "sticky" σ-methane ligand. The efficiency of this nontrivial process has been attributed to the spatial orientation of functional groups that operate in concert to activate a water molecule and then achieve a multistep proton walk from water to an uncoordinated pyrazolyl nitrogen atom, to the methyl ligand, and then back to the nitrogen atom and water. The overall proton-exchange process has been proposed to involve an initial attack of water at the CO ligand in 1 with concerted deprotonation by the uncoordinated pyrazolyl nitrogen atom. The pyrazolium proton is then transferred to the Pt-CH₃ bond, leading to a σ-methane intermediate. Subsequent rotation and deprotonation of the a-methane ligand, followed by reformation of 1 and water, result in scrambling of the methyl protons with the hydrogen atoms of water. An alternative two-step process that involves oxidative addition and reductive elimination has also been considered. The two competing mechanistic routes from 1 into [D₃]-1, as well as the conversion of 1 into [TpPt(CH₃)H₂] (2), have been examined by density functional theory (DFT) using a variety of exchange-correlation methods, primarily PW6B95, which was recently shown to be highly accurate for evaluating reactions of late-transition-metal complexes. The key role played by the free pyrazolyl nitrogen atom, acting as a proton carrier that abstracts a proton from water and transfers the proton to the Pt-CH₃ bond, is reminiscent of the dual functionality of histidine in the catalytic triad of natural serine proteases.