Publications

The ability to control the icing temperature of supercooled water (SCW) is of supreme importance in subfields of pure and applied sciences. The ice freezing of SCW can be influenced heterogeneously by electric effects, a process known as electrofreezing. This effect was first discovered during the 19th century; however, its mechanism is still under debate. In this Account we demonstrate, by capitalizing on the properties of polar crystals, that heterogeneous electrofreezing of SCW is a chemical process influenced by an electric field and specific ions. Polar crystals possess a net dipole moment. In addition, they are pyroelectric, displaying short-lived surface charges at their hemihedral faces at the two poles of the crystals as a result of temperature changes. Accordingly, during cooling or heating, an electric field is created, which is negated by the attraction of compensating charges from the environment. This process had an impact in the following experiments. The icing temperatures of SCW within crevices of polar crystals are higher in comparison to icing temperatures within crevices of nonpolar analogs. The role played by the electric effect was extricated from other effects by the performance of icing experiments on the surfaces of pyroelectric quasi-amorphous SrTiO₃. During those studies it was found that on positively charged surfaces the icing temperature of SCW is elevated, whereas on negatively charged surfaces it is reduced. Following investigations discovered that the icing temperature of SCW is impacted by an ionic current created within a hydrated layer on top of hydrophilic faces residing parallel to the polar axes of the crystals. In the absence of such current on analogous hydrophobic surfaces, the pyroelectric effect does not influence the icing temperature of SCW. Those results implied that electrofreezing of SCW is a process influenced by specific compensating ions attracted by the pyroelectric field from the aqueous solution. When freezing experiments are performed in an open atmosphere, bicarbonate and hydronium ions, created by the dissolution of atmospheric CO₂ in water, influence the icing temperature. The bicarbonate ions, when attracted by positively charged pyroelectric surfaces, elevate the icing temperature, whereas their counterparts, hydronium ions, when attracted by the negatively charged surfaces reduce the icing temperature. Molecular dynamic simulations suggested that bicarbonate ions, concentrated within the near positively charged interfacial layer, self-assemble with water molecules to create stabilized slightly distorted \u201cice-like\u201d hexagonal assemblies which mimic the hexagons of the crystals of ice. This occurs by replacing, within those ice-like hexagons, two hydrogen bonds of water by C−O bonds of the HCO₃⁻ ion. On the basis of these simulations, it was predicted and experimentally confirmed that other trigonal planar ions such as NO₃⁻, guanidinium⁺, and the quasi-hexagonal biguanidinium⁺ ion elevate the icing temperature. These ions were coined as \u201cice makers\u201d. Other ions including hydronium, Cl⁻, and SO₄⁻² interfere with the formation of ice-like assemblies and operate as \u201cice breakers\u201d. The higher icing temperatures induced within the crevices of the hydrophobic polar crystals in comparison to the nonpolar analogs can be attributed to the proton ordering of the water molecules. In contrast, the icing temperatures on related hydrophilic surfaces are influenced both by compensating charges and by proton ordering(Figure Presented).

Symmetry-imposed restrictions on the number of available pyroelectric and piezoelectric materials remain a major limitation as 22 out of 32 crystallographic material classes exhibit neither pyroelectricity nor piezoelectricity. Yet, by breaking the lattice symmetry it is possible to circumvent this limitation. Here, using a unique technique for measuring transient currents upon rapid heating, direct experimental evidence is provided that despite the fact that bulk SrTiO3 is not pyroelectric, the (100) surface of TiO2-terminated SrTiO3 is intrinsically pyroelectric at room temperature. The pyroelectric layer is found to be ≈1 nm thick and, surprisingly, its polarization is comparable with that of strongly polar materials such as BaTiO3. The pyroelectric effect can be tuned ON/OFF by the formation or removal of a nanometric SiO2 layer. Using density functional theory, the pyroelectricity is found to be a result of polar surface relaxation, which can be suppressed by varying the lattice symmetry breaking using a SiO2 capping layer. The observation of pyroelectricity emerging at the SrTiO3 surface also implies that it is intrinsically piezoelectric. These findings may pave the way for observing and tailoring piezo- and pyroelectricity in any material through appropriate breaking of symmetry at surfaces and artificial nanostructures such as heterointerfaces and superlattices.

Crystals are physical arrays delineated by polar surfaces and often contain imperfections of a polar nature. Understanding the structure of such defects on the molecular level is of topical importance since they strongly affect the macroscopic properties of materials. Moreover, polar imperfections in crystals can be created intentionally and specifically designed by doping nonpolar crystals with \u201ctailor-made\u201d additives as dopants, since their incorporation generally takes place in a polar mode. Insertion of dopants also induces a polar deformation of neighboring host molecules, resulting in the creation of polar domains within the crystals. The contribution of the distorted host molecules to the polarity of such domains should be substantial, particularly in crystals composed of molecules with large dipole moments, such as the zwitterionic amino acids, which possess dipole moments as high as ∼14 D. Polar materials are pyroelectric, i.e., they generate surface charge as a result of temperature change. With the application of recent very sensitive instruments for measuring electric currents, coupled with theoretical computations, it has become possible to determine the structure of polar imperfections, including surfaces, at a molecular level. The detection of pyroelectricity requires attachment of electrodes, which might induce various artifacts and modify the surface of the crystal. Therefore, a new method for contactless pyroelectric measurement using X-ray photoelectron spectroscopy was developed and compared to the traditional periodic temperature change technique. Here we describe the molecular-level determination of the structure of imperfections of different natures in molecular crystals and how they affect the macroscopic properties of the crystals, with the following specific examples: (i) Experimental support for the nonclassical crystal growth mechanism as provided by the detection of pyroelectricity from near-surface solvated polar layers present at different faces of nonpolar amino acid crystals. (ii) Enantiomeric disorder in dl-alanine crystals disclosed by detection of anomalously strong pyroelectricity along their nonpolar directions. The presence of such disorder, which is not revealed by accurate diffraction techniques, explains the riddle of their needlelike morphology. (iii) The design of mixed polar crystals of l-asparagine·H2O/l-aspartic acid with controlled degrees of polarity, as determined by pyroelectricity and X-ray diffraction, and their use in mechanistic studies of electrofreezing of supercooled water. (iv) Pyroelectricity coupled with dispersion-corrected density functional theory calculations and molecular dynamics simulations as an analytical method for the molecular-level determination of the structure of polar domains created by doping of α-glycine crystals with different l-amino acids at concentrations below 0.5%. (v) Selective insertion of minute amounts of alcohols within the bulk of α-glycine crystals, elucidating their role as inducers of the metastable β-glycine polymorph. In conclusion, the various examples demonstrate that although these imperfections are present in minute amounts, they can be detected by the sensitive pyroelectric measurement, and by combining them with theoretical computations one can elucidate their diverse emerging functionalities.

The riddle of anomalous polar behavior of the centrosymmetric crystal of α-glycine is resolved by the discovery of a polar, several hundred nanometer thick hydrated layer, created at the {010} faces during crystal growth. This layer was detected by two independent pyroelectric analytical methods: (i) periodic temperature change technique (Chynoweth) at ambient conditions and (ii) contactless X-ray photoelectron spectroscopy under ultrahigh vacuum. The total polarization of the surface layer is extremely large, yielding ≈1 μC·cm^-2, and is preserved in ultrahigh vacuum, but disappears upon heating to 100 °C. Molecular dynamics simulations corroborate the formation of polar hydrated layers at the sub-microsecond time scale, however with a thickness of only several nanometers, not several hundred. This inconsistency might be reconciled by invoking a three-step nonclassical crystal growth mechanism comprising (i) docking of clusters from the supersaturated solution onto the evolving crystal, (ii) surface recognition and polar induction, and (iii) annealing and dehydration, followed by site-selective recrystallization.

This cooperative endeavour first describes early studies in chemical crystallography, encompassing molecular packing modes, characterization of weak hydrogen bonds, the engineering of functional crystals and monitoring of reaction pathways in molecular crystals by x-ray and neutron diffraction. With the design of 'tailor-made' auxiliary molecules, it became possible to correlate molecular enantiomerism and crystal enantiomorphism, to control the early stages of crystal nucleation, to resolve enantiomers by crystallization, induce the precipitation of metastable polymorphs, and shed light on the role played by solvent on crystal growth. With such auxiliaries, the structure of mixed crystals was revised and the ability to perform 'absolute' asymmetric synthesis in host centrosymmetric crystals demonstrated. With the introduction of grazing incidence synchrotron x-ray diffraction from liquid surfaces it also became possible to design and characterize crystalline thin film architectures at the air-water interface providing a general insight on the mechanism of crystal nucleation at the molecular level, in particular that of ice and cholesterol. Finally the collective knowhow from these studies were crucial for obtaining homochiral peptides prepared from the polymerization of racemates of amphiphilic amino acids dissolved in aqueous solution, and for experiments towards elucidating the pathological crystallization of cholesterol and the malaria pigment in Plasmodium-infected red blood cells.

Crystal specimens of the γ-polymorph of achiral glycine which crystallize in space groups P3₁ and P3₂ as determined by the anomalous X-ray scattering method are shown to be laevorotatory and dextrorotatory, respectively, as determined by optical rotation of the crystals.

Rub-a-dub-dub: The hypothesis of contact electrification through the transfer of cryptoelectrons was tested by scrutinizing the evidence for the reduction of Pd²⁺ and Cu²⁺ by static charges on rubbed Teflon. X-ray photoelectron spectroscopy studies indicated that neither of these ions is reduced (see picture; black: Pd²⁺ adsorbed, red: Pd ⁰ adsorbed and then reduced by formadehyde, green: mixture of Pd ²⁺ and Pd⁰ arising from partial reduction after 2 h under the XPS probe) by the static charge. The presented alternative interpretation challenges the role of cryptoelectrons.

Glycine nanocrystals, grown in aligned nanometer-scale cylindrical pores of nanoporous polystyrene-poly(dimethyl acrylamide) monoliths by evaporation of imbibed aqueous solutions, adopt preferred orientations with their fast-growth axes aligned parallel with the pore direction. X-ray diffraction analysis revealed the exclusive formation of the metastable β-polymorph, with crystal size comparable with the 22 nm pore diameter, in contrast to the formation of a-glycine in the absence of nanoscale confinement. When grown from aqueous solutions alone, the nanocrystals were oriented with their [010] and [010] axes, the native fast growth directions of the (+) and (-) enantiomorphs of β-glycine, respectively, aligned parallel with the pore direction. In contrast, crystallization in the presence of racemic mixtures of chiral auxiliaries known to inhibit growth along the [010] and [010] directions of the enantiomorphs produced β-glycine nanocrystals with their [001] axes nearly parallel to the pore direction. Enantiopure auxiliaries that inhibit crystallization along the native fast growth direction of only one of the enantiomorphs allow the other enantiomorph to grow with the [010] axis parallel to the cylinder. Collectively, these results demonstrate that crystal growth occurs such that the fast-growing direction, which can be altered by adding chiral auxiliaries, is parallel to the pore direction. This behavior can be attributed to a competition between differently aligned crystals due to critical size effects, the minimization of the surface energy of specific crystal planes, and a more effective reduction of the excess free energy associated with supersaturated conditions when the crystal grows with its fast-growth axis unimpeded by pore walls. These observations suggest that the β-glycine nanocrystals form by homogeneous nucleation, with minimal influence of the pore walls on orientation.

As part of our studies on the biochirogenesis of peptides of homochiral sequence during early evolution, the formation of oligopeptides composed of 14-24 residues of the same handedness in the polymerization of DL-leucine (Leu), DL-phenylalanine (Phe), and DL-valine (Val) in aqueous solutions, by activation with N,N-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled α-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of β-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the β-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-¹N-Me-histidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-α-amino acids, the long oligopeptides were composed mainly from oligo-L-Leu and oligo-D-Ile in the first system and oligo-D-Phe in the second. Furthermore, in the polymerization of mixtures of hydrophobic racemic α-amino acids DL-Leu, DL-Val, and DL-Phe and with added racemic DL-alanine and DL-tyrosine, copeptides of homochiral sequences are most dominantly represented. Possible routes for a spontaneous "mirror-symmetry breaking" process of the racemic mixtures of homochiral peptides are presented.

A method for direct assignment of the absolute configuration of molecules and the absolute structures of polar crystals, independent to that of Bijvoet, is described. The method correlates between the two-dimensional packing arrangement of specific faces, that delineate crystals during their growth and dissolution, with molecules present in the environment. The structural information stored in these faces is transferred to "tailor-made" molecules added to the solvent by controlled morphological changes induced to the growing crystals and by the creation of etch pits at specific crystal faces during their dissolution. In addition, the "tailor-made" molecules are occluded enantioselectively as guests within specific sectors of the host crystals. The method is illustrated for a variety of molecules and crystals including the assignment of the absolute configuration of several α-amino acids as "tailor-made" additives in centrosymmetric crystals of glycine and serine, for the absolute structure of polar crystals of sugars and α-amino acids and consequently the absolute configuration of molecules packed in such crystals.

This chapter contains sections titled:IntroductionGeneration and Amplification of Chirality in the Solid StateSelfAggregation of Amphiphilic Molecules at AirSolution InterfacesMolecular Recognition During Crystal NucleationChiral Amplification in The System GlycineSoluble CYAmino AcidsConclusion and Outlook

(Graph Presented) A pattern on the sheets: Long oligopeptides of homochiral sequence (see mass spectrum of enantioselectively deuterated compounds) were obtained in the polymerization of racemic N-carboxyanhydrides of valine (ValNCA) or leucine (LeuNCA) in aqueous solutions, through self-assembly into racemic antiparallel β-sheet templates.

In a recent paper, Srinivasan and Sherwood reported that α-resorcinol crystals grow unidirectionally at the {011} faces in the vapor phase and suggested that this phenomenon of unidirectional growth is intrinsic to polar crystals. Here, we present a molecular modeling study suggesting a plausible "self-poisoning" mechanism that may explain the unidirectional growth of α-resorcinol in the vapor phase, a process that does not exclude the inhibition of crystal growth by solvent.

The control of crystal polymorphism of the trimorphic crystals of glycine (Gly) grown in aqueous solutions in the presence of α-amino acids operating as stereospecific nucleation inhibitors is reported. The presence of enantiopure α-amino acids phenylalanine (Phe), methionine (Met), and tryptophan (Trp) in the crystallizing aqueous solutions induces changes in the morphology of α-Gly leading to the formation of pyramidal instead of bipyramidal crystals. Increased concentrations of racemic Phe and Met inhibit both the α- and β-polymorphs of glycine and induce precipitation of the thermodynamically most stable γ-polymorph. α-Amino acids that bear bulky side groups such as racemic tryptophan (Trp), N-CH₃-Trp, and α-naphthylalanine induce precipitation of the least stable β-Gly polymorph. Quasi-racemic mixtures of R-Trp and S-Phe (or S-Met), for example, lead to the precipitation of one of the enantiomorphs of β-Gly. The roles played by the different α-amino acids in affecting morphology and polymorphism are discussed in terms of their interactions with and stereoselective occlusion in the various sectors of the {010} faces of the β-Gly crystals.

The formation of diastereoisomeric libraries of oligopeptides through the heterogeneous polymerization of racemic crystals of phenylalanine N-carboxyanhydride (PheNCA) is reported. The diastereoisomeric compositions of the oligopeptides formed on polymerization of (R,S) crystals incorporating the deuterium-tagged S enantiomer were determined by MALDI-TOF mass spectrometry. The racemic mixtures of the oligopeptides longer than pentamers are represented primarily by diastereoisomers of homochiral sequence and with peptides containing only one heterochiral repeating unit. A mechanism comprising the following three sequential steps to account for this unusual observation is proposed: 1) formation of dimers and trimers at a partially damaged liquid/ solid interface, 2) chain propagation that takes place within the bulk of the crystal through a lattice-controlled "zipper-like" mechanism between homochiral molecules arranged in a head-to-tail motif to yield crystalline antiparallel β-sheets of alternating oligopeptide chains of homochiral sequence of opposite handedness, and 3) enantiomeric cross-inhibition that results in chain termination. Induced desymmetrization of the racemic mixtures of the formed peptides was achieved by the polymerization of the mixed quasi-racemic crystals of (R)-PheNCA, ((S)-PheNCA), and (S)-ThieNCA (3-(2-thienyl)-alanine N-carboxyanhydride) of various compositions. These experiments resulted in the formation of non-racemic libraries of oligopeptides composed of homochiral chains of (R)-Phe and copolymers of randomly distributed (S)-Phe and (S)-Thie sequences. From these findings, we propose a stochastic model for the generation of libraries of nonracemic mixtures of oligopeptides from the polymerization of host (R,S)-PheNCA with racemic mixtures of other guest NCA amino acids dissolved in limited quantities in the crystal.

Cholesteryl-L-glutamate (CLG) thin films were investigated when deposited on pure water and on saturated solutions of water soluble amino acids, to test the capacity of the CLG monolayer to recognize and incorporate amino acids from the subphase. Analysis of grazing incidence X-ray diffraction measurements indicates that the hydrophobic amino acids, leucine, isoleucine, and valine, are adsorbed between the glutamate moieties, within the CLG crystalline monolayer, but also around their domains, forming, for L-Leu and D-Val, crystalline bilayers. The presence of Cu²⁺ ions in the aqueous subphase enhances the crystallinity of the CLG monolayer without overly affecting the lateral packing, by bridging glutamate moieties on neighbor molecules. When amino acids are injected in a Cu²⁺ containing solution, the domain size of the mixed monolayers formed with the CLG molecules and hydrophobic amino acids is drastically increased.

CdS quantum particles (QPs) assembled at predetermined distances from a gold substrate are prepared within a Langmuir-Blodgett film that forms an organic host matrix. The system is characterized by controlled surface charging (CSC) in X-ray photoelectron spectroscopy (XPS) and complementary methods, successfully resolving the discrete QP layers. A quantitative study of substrate-QPs charge-transfer channels is provided by laser-intensity dependent contact potential difference (CPD) measurements. The extracted electron-transfer rate constants exhibit marked differences in electron transfer from the film toward the substrate versus the backward process. The charging of the hybrid film was found to be either negative or positive depending on the intensity of the laser that photoexcites the QPs.

In this review, the delicate interplay between stereochemical control, monitoring at the subnanometer level, and an understanding of crystal nucleation is probed. Control of crystal nucleation may be achieved employing tailor-made auxiliaries, which are either nucleation inhibitors or promoters. The process may be monitored at an interface via grazing incidence X-ray diffraction (GIXD). By these means, we can glean experimental knowledge of crystal nucleation in various molecular systems. A hypothesis was invoked that supersaturated solutions containing molecular clusters adopt various arrangements and shapes, some of which resemble the crystals into which they develop. This hypothesis was taken advantage of for the design of tailored inhibitors in achieving kinetic resolution of enantiomers and induced precipitation of particular crystal polymorphs. The control and behavior of polymorphic crystallization may be understood at the molecular level through the interplay between inhibitor, solvent, solute, crystal and layer lattice energies, as well as surface layer structures. With respect to promotion of crystal nucleation, it may be achieved by Langmuir monolayers at the air-aqueous solution interface, acting as a templating agent. Determination of the monolayer crystal structure by GIXD yields the extent and nature of the complementary fit between nucleator and nucleant. Finally, GIXD was applied to monitor by a snapshot technique the layer-by-layer crystalline assembly of cholesterol molecules at the air-water interface, which involved changes in molecular packing as the film grew in thickness.

A grazing-incidence X-ray-diffraction (GIXD) study of the self-assembly, on water, of nonracemic γ-stearyl glutamic acid (pure or as a mixture with racemic or (S)-1,2 -dipalmitoyl-glycero-3-phosphoethanolamine (DPPE)) demonstrated a phase separation of the α-amino acid amphiphile into racemic and enantiomorphous two-dimensional crystallites within the phospholipid domains. The packing arrangements of the two α-amino acid crystalline phases were identical to those found in the absence of DPPE and have been determined, at almost atomic resolution, by X-ray structure-factor calculations. By contrast, racemic and nonracemic N^ε -stearoyllysine spontaneously segregated into two-dimensional enantiomorphous domains within the DPPE environment that induced a change in the tilt direction of the hydrocarbon chains of the α-amino acid molecules. Phase separation of nonracemic amphiphiles, originating from preferred lateral homochiral or heterochiral intermolecular interactions, is in agreement with the formation of enantiomerically pure or enriched homochiral oligopeptides in overrepresented amounts in the polycondensation of activated nonracemic amphiphilic α-amino acids on plain water or within phospholipid monolayers.

We investigated the electronic properties of hybrid inorganic/organic thin films where the inorganic components are monodisperse CdS quantum size particles (diameters 2.5 and 5 nm). For this purpose, low-energy photoelectron spectroscopy was applied in which the energy of photoelectrons, ejected from the metal substrate or from the films themselves, is measured. The electronic properties of hybrid Langmuir-Blodgett films were studied, when the films were deposited on gold or silicon surfaces and contained particles of different sizes arranged in layers at different distances from the substrate. For comparison films containing only the organic matrix were examined, so the effect of the quantum particles (QPs) on the electronic properties of the whole film could be resolved. The present study proves the importance of the organization of hybrid structure on its electronic properties. It is clearly demonstrated that the QPs cannot be considered as insolated species and that their electronic properties are affected by the structure of the film as a whole and by the substrate. It is shown that the QP size affects both the photoelectron emission yield and the scattering efficiency of electrons from the QPs.

The feasibility of generating oligopeptides with homochiral sequence via lattice-controlled polymerization of racemic mixtures of precursor molecules that undergo spontaneous segregation into two-dimensional (2-D) enantiomorphous domains at the air-aqueous solution interface was analyzed. For model systems, we studied the polymerization reaction within 2-D crystalline domains of mixtures of (R,S)-N^εstearoyl-thio-lysine with ∼10% (R,S)-N^ε-stearoyl-lysine, and (R,S)-N^α-carboxyanhydride of N^ε-stearoyllysine. According to in situ grazing incidence X-ray diffraction (GIXD) measurements at the air-water interface, the molecules form 2-D crystallites packing by translation symmetry only. Oligopeptides 4-6 units long were obtained at the air-solution interface after injection of an appropriate catalyst into the subphase. The course of the chemical transformations was monitored by GIXD. The distribution of the diastereoisomeric oligopeptides was determined by matrix-assisted laser-desorption ionization time-offlight (MALDI-TOF MS) mass spectrometry on samples prepared from precursor molecules enantioselectively labeled with deuterium. The experimental relative abundance of oligopeptides with homochiral sequence was found to be larger than that calculated for a theoretical random process, yielding an excess by a factor of 2.5-3.5 for the tetra- to hexapeptides. The present studies may be relevant for probing the role that might have been played by ordered clusters at interfaces for the generation of homochiral oligopeptides under prebiotic conditions.

Composite materials of quantum particles (Q-particles) arranged in layers within crystalline powders of π-conjugated, rodlike dicarboxylic acids are reported. The synthesis of the composites, either as three-dimensional crystals or as thin films at the air-water interface, comprises a two-step process: 1) The preparation of the Cd salts 6(Cd), 8(Cd) or Pb salts 6(Pb), 8(Pb) of the oligo(p-phenyleneethynylene)dicarboxylic acids 6(H), 8(H), in which the metal ions are arranged in ribbons and are separated by the long axis of the organic molecules, as demonstrated by X-ray powder diffraction analysis of the solids and grazing incidence X-ray diffraction analysis of the films on water. 2) Topotactic solid/gas reaction of these salts with H₂S to convert the metal ions into Q-particles of CdS or PbS embedded in the organic matrix that consists of the acids 6 (H) and 8 (H). These hybrid materials have been characterized by X-ray photoelectron spectroscopy and transmission electron microscopy.

Five bifunctional alpha -amino acid-epsilon -carboxy bolaamphiphiles [(2-RS, or RS)-(HOOC)-(CH2)(m)-CONH-(CH2)(n)-CH(COOH)(NH2) m=20,22, n=3,4 labeled (l), (d,l)-C(22)Orn (l), (d), (d,l)-C(22)Lys, (d,l)-C(24)Lys respectively] were synthesized. These molecules were deposited on different aqueous subphases, and studied by means of grazing incidence X-ray diffraction (GIXD). On deionized water, the bolaamphiphiles (dl)-C(22)Lys yield a mixture of crystallites: both a monolayer, in which the chains are tilted from the normal, and a multilayer in which the molecules lie parallel to the water. On the other hand, when deposited on mono- or bi-metal ionic subphases, they self-assemble into crystalline multilayer films in which the molecules lie parallel to the aqueous solution surface, linked head-to-head and tail-to-tail in the form of extended chains. The latter are juxtaposed such that the metal ions form sheets separated by the organic molecules, aligned perpendicular to the plane of the aqueous solution. Deposition of either the enantiomerically pure or racemic bifunctional bolaamphiphiles on an aqueous solution of mixed Cu(Acetate)(2) and Pb(Acetate)(2), yields self-assembled crystalline films composed of the two different metal cations, arranged in alternating sheets, separated by the organic spacer. Both GIXD and X-ray-photoelectric-spectroscopy (XPS) studies (after deposition on solid support) demonstrate that the structures of these films differ form the ones formed on either pure Pb(Ac)(2) or on Cu(AC)(2) solutions, thus excluding the simultaneous formation of the two monometallic crystalline phases.

Cholesterol and some cholesterol-like derivatives such as stigma-sterol and cholesterol acetate self-assemble into semicrystalline monolayers, bilayers, or trilayers on the surface of water, as has been reported previously. Here we have extended our thin film studies toward cholesteryl esters that, in their bulk crystals, pack as interdigitated bilayers due to the mismatch between the cross-sectional area of the rigid cholesterol moiety (40 Ų) and the attached hydrocarbon chain (20 Ų). As shown by grazing incidence X-ray diffraction (GIXD), cholesteryl esters spontaneously self-assemble on the surface of water in order to form interdigitated bilayer films. The unit cell parameters of such bilayers at the water surface almost match those of their three-dimensional counterparts. Other experiments such as surface pressure vs area per molecule isotherms and ellipsometry measurements corroborate this result. To control the growth of the interdigitated films, we have used "tailor-made" additives (long-chain alcohols or acids) that fill the voids in the chain region of the cholesteryl ester layer caused by the structural mismatch, thereby inhibiting interdigitation. Using this strategy, we were able to form a mixed monolayer composed of the ester and the additive molecules in a 1:1 ratio, where the hydrocarbon chain of additive molecule intercalates between the ester chains and effectively inhibits the growth of the interdigitated bilayer.

The electronic properties of hybrid Langmuir-Blodgett (LB) films deposited on gold surfaces containing CdS particles of different sizes arranged in layers within the cascade-like arhitectures were studied by applying low-energy photoelectron spectroscopy (LEPS). It was demonstrated that thio acids can be applied to prepare stable hybrid films.

The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a trilayer, composed of a highly crystalline bilayer in a rectangular lattice and a disordered top cholesterol layer. This system undergoes a phase transition into a crystalline trilayer incorporating ordered water between the hydroxyl groups of the top and middle sterol layers in an arrangement akin to the triclinic 3-D crystal structure of cholesterol · H₂O. By comparison, the cholesterol derivative stigmasterol transforms, upon compression, directly into a crystalline trilayer in the rectangular lattice. These results may contribute to an understanding of the onset of cholesterol crystallization in pathological lipid deposits.

Electrostatic interactions between amidinium and carboxylates were used for the construction of interdigitated architectures at the air-solution interface. Spreading the water-insoluble amphiphile p-pentadecylbenzoic acid (A) on an aqueous solution of p-methylbenzamidinium (B) ions results in an intercalation of the water-soluble base between the acidic headgroups of the water-insoluble amphiphile to form an amorphous A-B-A-B monolayer according to grazing incidence X-ray diffraction (GIXD) and X-ray reflectivity measurements. Upon compression the monolayer transforms into a crystalline film composed of three bilayers with interdigitated hydrocarbon chains, and a top layer whose chains are disordered. Water-insoluble p-heptadecylbenzamidinium spread on an aqueous solution of benzoic acid displays a surface pressure-area isotherm similar to that obtained from the above system. A mechanism that accounts for the formation of these films is presented. Deposition of p-heptadecylbenzamidinium and p-pentadecylbenzoic acid amphiphiles in a 1:1 ratio on pure water led to the formation of a crystalline monolayer phase but which is partially disordered. Over an aqueous solution containing a 1:1 mixture of benzamidinium and benzoic acid no measurable binding of these solute molecules to the polar headgroups of the 1:1 mixed monolayer could be detected by X-ray reflectivity or GIXD.

The absolute orientations of the amphiphilic molecules α-hydroxy ω-bromo alcohols BrC_nH_2n OH, n= 21, 22, and the alkyl hydroxy esters C_mH_2m+1COO(CH₂)_nOH, m = 14, 15, n = 10, in crystalline monolayer forms on water have been determined, the former by grazing incidence X-ray diffraction (GIXD) and the latter by sum frequency generation (SFG). The assignment was made for the alkyl hydroxy esters by establishing the polar angle between the terminal CH₃-C bond and the normal to the plane of the monolayer; for the bromo alcohols the assignment was made by a determination of the two-dimensional crystal structure via X-ray structure factor calculations. The SFG results are in agreement with reported GIXD and lattice energy analyses of the alkyl hydroxy esters m = 19, n = 9, 10. These studies have further revealed the absolute orientation of the alcohol C-OH bonds at the water surface, which in turn can be correlated with the ice-nucleating behavior of the monolayers on supercooled water drops in terms of the odd and even values of n.

Insertion of the 1,3-bis(ethynylene)benzene unit as a rigid spacer into a linear alkyl chain, thus separating the two resulting stems by 9 Å, induces chain folding at the air-water interface. These folded molecules self-assemble into crystalline monolayers at this interface, with the plane of the folding unit almost perpendicular to the water surface, as determined by synchrotron grazing-incidence X-ray diffraction. Three distinct molecular shapes, of the types U, inverted U, and M, were obtained in the two-dimensional crystal-line state, depending upon the number of spacer units, and the number and position of the hydrophilic groups in the molecule. The molecules form ribbons with a higher crystal coherence in the direction of stacking between the molecular ribbons, and a lower coherence along the ribbon direction. A similar molecule, but with a spacer unit that imposes a 5 Å separation between alkyl chains, yields the conventional herring-bone arrangement.

The packing arrangements of Langmuir films on aqueous solution of simple amphiphiles, such as fatty acids, alcohols, amides, and amino acids, are now established to near atomic resolution by the method of grazing incidence X-ray diffraction (GIXD), complemented by various spectroscopic and lattice energy computational techniques. For simple aliphatic chainlike amphiphilic molecules, it is possible to correlate the extent of two-dimensional (2-D) crystallinity of the Langmuir film with molecular interactions, in terms of the nature and length of the hydrophobic chain, the type of hydrophilic headgroup, and the binding properties thereto of solute ions and molecules from the aqueous subphase. The monolayer packing arrangements of amphiphilic molecules can be engineered for the performance of photoinduced topochemical reactions, and characterized by GIXD. Racemic mixtures of amphiphiles can also be engineered, by taking advantage of intermolecular hydrogen bonding, to undergo a spontaneous separation of the left- and right-handed molecules into 2-D chiral crystals at the air-solution interface. The geometry of binding of molecules or ions from the aqueous subphase to the hydrophilic headgroups can be pinpointed by GIXD, in favorable systems. The ordered binding of solutes to the amphiphile monolayer can lead to induced nucleation of oriented organic and inorganic crystals at the solution interface. GIXD has shown that such an induction can occur via even a partial lattice match, or by structural complementarity, sometimes involving a molecular rearrangement of the amphiphiles. It is possible from monolayer-induced crystallization to glean information on the process of nucleation and on the critical size of the nuclei. A variety of different types of crystalline multilayers, composed of water-insoluble molecules such as bolaform amphiphiles, alkanes, heterosubstituted aromatics, can be formed at the air-solution interface. The number of layers formed and their polymorphic behavior can be controlled, albeit within limits, with the use of tailor-made additives. Their structures can be determined by GIXD, thus providing data on the initial stages of 3-D crystalization. Multilayers, comprising water-insoluble and water-soluble components, assembled in situ at the solution surface leading to thin film supramolecular architectures, have been engineered. These crystals have been found to be oriented vis-à-vis the solution surface and thus amenable to characterization by GIXD and other methods.

In 1848 Louis Pasteur manually separated enantiomorphous three- dimensional crystals. A 2D analogue of this experiment involving clusters of 1-nitronaphthalene bound to a gold surface has been recently performed by the research groups of Berndt and Schneider. The general principles governing separation of enantiomers from 3D crystals to 2D clusters at interfaces, and their characterization, are discussed.

On studies of large scale optical resolution by crystallization, it was found that α-amino acid salts crystalline in the form of conglomerates. The conglomerates were composed of lamellar twins, hence are not amenable to large scale resolution. By conducting further studies, it was found that the occurrence of the lamellar twins can be prevented with the assistance of 'tailor-made' enantioselective crystal nucleation inhibitors that allow the resolution of hydrophobic racemic α-amino acids by kinetic crystallization.

The assembly, orientation, and structural features of nanoscale tubes composed of cyclic peptides, formed at the air-water interface, were detected by grazing incidence X-ray diffraction (GIXD). The peptide cyclo-[(L-Phe-D- N-MeAla-)₄] (1) exhibits two-dimensional crystallinity in which the plane of the peptide ring is parallel to the water interface. The peptide cyclo-[(L- Trp-D-Leu)₃-L-Ser-D-Leu] (2) forms predominantly planar aggregates composed of several tubes, lying with their long axes parallel to the air-water interface. In contrast, the peptide cyclo-[(L-Trp-D-Leu)₄] (3) exhibits a very low tendency to form ordered two-dimensional arrays of nanotubes. Films of peptides 2 and 3 as well as their mixtures with the phospholipid DPPA were transferred onto a solid support and visualized by scanning force microscopy (SFM).

Ordered molecular clusters with a length scale down to few nanometers are currently attracting wide attention in the physical and biological sciences. The design and preparation of functional materials such as thin-layered microstructures, reagent films for biosensors, and devices for optoelectronicsrequires knowledge and control of nanoarchitectures from the very early stages of self-organization. This requirement touches upon the control of nucleation, growth, morphology and structure of crystals, particularly at interfaces. The recent development of various methods for the elucidation of molecular ordering at interfaces provides a means to probe the early stages of molecular assembly. One route involves the spontaneous formation, at the air-water interface, ofcrystalline films ranging from one to several layers thick, composed of water-insoluble molecules in pure form or complexed with water-soluble ions ormolecules from the aqueous subphase. In this review much use is made of grazing incidence X-ray diffraction (GIXD) using synchrotron radiation that provides structural information at the subnanometer scale of crystalline films at the air-liquid interface [1,2]. The topics described here shall encompass the spontaneous separation of racemates of amphiphilic molecules into enantiomorphous two-dimensional (2D) domains, the formation of alkane multilayers, the assembly of trilayers containing interdigitated molecules, the self-organization of supramolecular thin film architectures, the early stages of crystalline aggregation of cholesterol, and the organization of channel-forming molecules.

The structure of monolayers of the n-alkane C₅₀H₁₀₂ on water was studied. The orientational, conformational and packing properties of these molecules were explored on the water surface by reflection-absorption Fourier transform infrared spectroscopy (FT-IR) and grazing incidence X-ray diffraction (GIXD) directly on the water surface, as well as by cryo-TEM on vitreous ice and scanning force microscopy (SFM) of the films transferred onto mica support.

The structure of mixed Langmuir films of the normal alkane C₃₂H₆₆ with different quantities of the normal alcohol C₃₁H₆₃OH or the diol HO(CH₂)₃₀OH on pure water were determined in situ by applying surface-sensitive methods that include grazing incidence X-ray diffraction (GIXD) and infrared reflection - absorption spectroscopy (IRRAS) and by induced freezing of water drops. Random solid solutions were formed between the alkane and C₃₁H₆₃OH. On the other hand, segregation of the two components was observed in the mixed systems of the alkane and HO(CH₂)₃₀OH. These findings suggest new ways for the design of hydrophobic surfaces bearing hydrophilic sites, which may be appropriate for epitaxial ice nucleation and cloud seeding purposes.

A direct relationship between the structures of two-dimensional (2-D) crystallites of 4-octadecyloxy-E-cinnamic acid and 4-octadecyloxy-E- cinnamamide amphiphiles at the air-water interface and their photochemical behavior, is presented. The detailed packing arrangements of the monolayers were determined, close to the atomic level, from the diffraction pattern measured, in situ on the water surface, by the grazing incidence X-ray diffraction (GID) technique using synchrotron radiation. The products of the photochemical reaction, performed by irradiating the monolayer films directly on the water surface, were collected and analyzed. While the acid crystallites yield a β-truxinic acid product together with the cis-isomer, the amide undergoes only trans-cis isomerisation, in full agreement with the 2-D crystalline packing arrangements of the two amphiphiles on the water surface.

Grazing incidence X-ray diffraction (GID) has been applied to the study of structural characteristics of two-dimensional crystallites of the ionophores valinomycin (VM) and nonactin (NA) when complexed with various cations at the air-solution interface. The VM complexes assume a bracelet shape that packs in a two-dimensional hexagonal unit cell. Other crystalline phases were formed on potassium iodide and barium perchlorate solutions. The presence of particular lipids induced ordered stacking of VM-potassium chloride complexes into three to four layers. NA packs in a pseudotetragonal unit cell on solutions of NH₄SCN and KSCN. Upon compression of the NA-NH₄SCN film, crystallites seven to eight layers thick were detected and the GID data enabled the determination of the structure. The tendency of these complexed ionophores to form multilayer crystallites at interfaces may have bearing on ion transport through membranes, via stacking.

The formation of Langmuir monolayers at the air water interface has long been believed to be limited to amphiphilic molecules containing a hydrophobic chain and a hydrophilic headgroup. Here we report the formation of crystalline mono- and multilayer self-assemblies of oligothiophenes, a class of aromatic nonamphiphilic molecules, self-aggregated at the air water interface. As model systems we have examined the de position of quaterthiophene (S₄), quinquethiophene (S₅), and sexithiophene (S₆) from chloroform solutions on tile water surface. The structures of the films were determined by surface pressure area isotherms, by scanning force microscopy (SFM after transfer of the films onto atomically smooth mica, by cryo-transmission electron microscopy (Cryo-TEM) on vitreous ice, and by grazing incidence synchrotron X-ray diffraction (GII) directly on the water surface. S₄ forms two polymorphic crystalline multilayers. In polymorph χ, of structure very similar to that of the three-dimensional solid, the molecules are aligned with their long molecular axis tilted by about 23 from the normal to the water surface. In polymorph β the long molecular axis is perpendicular to the water surface. S⁵ self-aggregates at tile water surface to form mixtures of monolayers and bilayers of the β polymorph: S₆, forms primarily crystalline monolayers of both χ and β forms. The crystalline assemblies preserve their integrity during transfer from the water surface onto solid supports. The relevance of the present results for the understanding of the early stages of crystal nucleation is presented.

Structure, morphology, and mechanical properties of mono- and several-layer structures of amphiphiles or pure n-alkane crystallites generated by spontaneous self-assembly on aqueous subphase have been analyzed by scanning force microscopy (SFM). Pure-component and heterogeneous mixtures of molecules were allowed to spread and self-assemble without compression on an aqueous subphase. The self-assembled films were transferred to an atomically smooth mica substrate by drainage for measurement using SFM. Results were compared with a variety of techniques including cryo-transmission electron microscopy, grazing incidence X-ray diffraction. X-ray reflectivity, and reflectance/absorption infrared spectroscopy. Whereas the collaborative techniques provide spatially-averaged information, we find that the SFM accesses both individual crystallites and amorphous material, thus providing unique information on the morphology, number of layers, and complementary structural features.

A systematic analysis of grazing incidence synchrotron Xray diffraction data of uncompressed amphiphilic alcohols C_nH_2n+1 OH (n = 31, 30, 23, 20, 19, 18, 16, 14, 13) on a water subphase at 5°C is presented. Pronounced structural changes were observed on reduction of chain length from n = 31 to 13. The relative amount of two dimensional (2D) crystalline material formed fell drastically; shorter crystalline coherence lengths were also observed. For n3118 the molecules are arranged in a rectangular cell (a ≈ 5 Å, b increases from ca. 7.4 to ca. 8.2 Å) with plane symmetry p1 g1. For n 2 and in the atomic displacement parameter parallel to the water surface; it increases from 0.1 Ų for n = 31 to 0.30 Ų for n = 19. We explain the preference for chain tilt along the b axis, rather than a, in terms of hydrogen bonding to the water subphase. The various structural properties of the C_nH_2n+2OH (n = 3113) monolayer series, such as degree of crystallinity and coherence length, lattice dimensions, chain orientation, and molecular motion, may be correlated with the icenucleating efficiency of these alcohol monolayers as a function of n.

Double layers are formed by α,ω-docosanediol (C22 diol) when it is spread on a water surface. The space group (a slightly relaxed form of P21/a) and the lattice parameters of the unit cell were determined by X-ray diffraction. Furthermore, multilayer formation was inhibited by addition of 10% of C24H49OH or 5% of HO(CH2)22OCH2Ph to the spreading solution. The coverage with the double layer was reduced to less than 15%; the rest was occupied by a monolayer.

A monolayer of 4-(octadecyloxy)benzoic acid at the air-solution interface has been used to induce oriented nucleation of three-dimensional (3-D) crystals of 4-hydroxybenzoic acid (HBA) monohydrate.¹ The two-dimensional (2-D) crystalline structure of this monolayer in a self-assembled uncompressed state, both on a water subphase and on a solution containing HBA, was determined by grazing incidence X-ray diffraction (GID) using synchrotron radiation. Crystalline domains of large coherence length were formed on water subphase at 14°C, and the fraction of the monolayer in the ordered state was much increased on HBA solution. The agreement between the observed and calculated GID data was found to be sensitive to the conformation and orientation of the monolayer molecules. These results demonstrate the ordered binding of the HBA solute to the amphiphile benzoic acid head groups to form hydrogen-bonded cyclic dimers between the two carboxylic acid moieties. The GID method was complemented by other surface sensitive techniques such as specular X-ray reflectivity, surface pressure-area isotherms, and nonlinear optics. A resulting model arrangement of the monolayer, based on the molecular packing, has been proposed for the induced nucleation of the 3-D crystals of 4-hydroxybenzoic acid monohydrate attached to the monolayer.

The spontaneous aggregation of the bolaamphiphile α,ωdocosanediol into embryonic threedimensional crystallites at the airwater interface can be inhibited by additives. A study with the aim of determining the necessary properties of such supplements is reported, which uses additives with molecular recognition properties and methods such as Xray reflectivity, cryotransmission electron microscopy, and atomic force microscopy in order to detect structural changes at the nanometer level.

Crystallization of R,S-alanine in the presence of small amounts of other resolved α-amino acids results in the precipitation of the racemic compound as twinned crystals displaying a propeller-like morphology of 222 symmetry, in contrast to needlelike crystals of mm2 symmetry when grown from pure aqueous solution. This unusual twinning is explained by assuming that the supersaturated solutions contain ordered clusters of structures akin to the mature crystals of (R,S)-, (R)-, and (S)-alanine. The resolved α-amino acid additive, e.g., R, stereospecifically inhibits growth of the R,S and R nuclei but not of the S nuclei. The latter serve as a template onto which the (R,S) crystals nucleate and grow. A model which takes into consideration the structural similarity between the racemic and chiral resolved forms of alanine to explain the twinning is presented. An X-ray diffraction analysis of a twinned crystal specimen is in agreement with a gradual change in structure, from a chiral crystal of space group P2₁2₁2₁ to the racemic compound of space group Pna2₁. To substantiate the model, crystals of alanine were grown from optically enriched solutions containing excess of one of the alanine enantiomers, which also induce the twinning phenomenon and an overall reduction in crystal symmetry. The relevance of these observations to the early stages of crystal nucleation is discussed.

The two-dimensional (2D) crystal structures of self-aggregated clusters of amphipbilic alcohols (C_nH_2n+1OH, n = 23, 30, 31, and C₁₉H₃₉CO₂(CH₂)_nOH, n = 9, 10) on pure water at a temperature of 5 °C have been determined to near-atomic resolution in order to understand the relative abilities of these monolayers to induce ice nucleation. The structures were solved making use of grazing incidence synchrotron X-ray diffraction (GID) data, complemented by lattice energy calculations. The GID data of the different monolayers within each of the two series (C_nH_2n+1OH, C₁₉H₃₉CO₂C_nH_2nOH) are very similar. The molecules pack in a rectangular unit cell of average dimensions a = 5.0 Å, b = 7.5 Å for the normal alcohols C_nH_2n+1OH and a = 5.7 Å, b = 7.5 Å for C₁₉H₃₉CO₂C_nH_2nOH. The plane group symmetry is essentially p1g1 for the normal alcohols C_nH_2n+1OH and essentially p1g1 for the other group. The molecular chains are tilted from the vertical by an average angle of 9°, in the direction of the b axis, for C_nH_2n+1OH and by 29°, in the direction of the a axis, for the other molecular type. The molecular chains related by glide (g) symmetry are arranged in a herringbone pattern. The fit to the Bragg rod intensity data of C_nH_2n+1OH permitted a reliable estimate of 0.07 Ų for the molecular mean-squared motion parallel to the water surface. The a bsolute orientations of the molecules C₁₉H₃₉CO₂C_nH_2nOH were determined by lattice energy calculations. The anisotropic coherence lengths of the crystallites of C₁₉H₃₉CO₂C_nH_2nOH derived from the widths of the two observed Bragg peaks have been correlated with the binding energies of molecules in different directions.

Two approaches are used to study suggested mechanisms for heterogeneous ice nucleation. In one, an epitaxial-like mechanism is studied by using Langmuir monolayers of aliphatic alcohols C n H 2n +1OH (n=16 to 31) spread on supercooled water drops. The packing arrangement of several of these uncompressed.monolayers on water, have been determined by grazing incidence x-ray diffraction (GID) and correlated with the structure of water molecules at the (001) face of hexagonal ice. The roles played by lattice match between the monolayers and ice, the coherence length of the amphiphile crystallites and the orientation of the hydroxyl groups at the interface in determining the nucleation efficiencies are specifically addressed. In another induced nucleation of ice by an electric field is studied using hydrophobic surfaces of chiral resolved and racemic α-amino acid crystals onto which water vapor has been condensed and nucleated into ice.

The spontaneous formation of highly crystalline two-dimensional films of uncompressed long chain amide and carboxylic acid amphiphiles spread on formamide has been demonstrated by grazing incidence X-ray diffraction. These results were compared to those found for the same amphiphiles on water. The observed diffraction data Of C29H59CONH2 over both water and formamide and those Of C29H59CO2H over formamide are strikingly similar, while those Of C29H59CO2H over water are different. Arachidamide (CH19H39CONH2) over water subphase forms a unimolecular layer with the molecules tilted by 18-degrees. Over formamide, the crystallites are made up, at least in part, of three molecular layers, with the molecules standing vertically. This was confirmed by X-ray specular reflectivity. These results are analogous to the well known, but as yet unexplained, influence which solvent may have on the growth of polymorphic modifications of three-dimensional crystals.

The method of cryo-transmission electron microscopy has been applied to study twinning behavior of mixed monolayers of 3-(eicosanoylamino) propionic acid and eicosanoamide spread on water and CdCl2 aqueous solution. The monolayers were deposited with a thin layer of aqueous subphase on grids which were vitrified by plunging into liquid ethane. Various electron diffraction patterns were observed and interpreted in terms of formation of two-dimensional (2-D) crystallites which display single and multiple twinning. Morphological features of the monolayer films were also obtained from bright and dark field images.

The advent of wellcollimated, highintensity synchrotron Xray sources and the consequent development of surfacespecific Xray diffraction and fluorescence techniques have recently revolutionized the study of Langmuir monolayers at the airliquid interface. These methods allowed for the first time the determination of the inplane and vertical structure of such monolayers with a resolution approaching the atomic level. We briefly describe these methods, including grazing incidence Xray diffraction, specular reflectivity, Bragg rods, standing waves, and surface fluorescence techniques, and review recent results obtained from them for Langmuir films. The methods have been successfully applied in the elucidation of the structure of crystalline aggregates of amphiphilic molecules such as alcohols, carboxylic acids and their salts, αamino acids, and phospholipids at the water surface. In addition, it became possible to monitor by diffraction the growth and dissolution of the crystalline selfaggregates as well as structural changes occurring by phase transitions. Furthermore, the surface Xray methods shed new light on the structure of the underlying ionic layer of attached solvent or solute species. Examples are given where singly or doubly charged ions bound to the twodimensional (2D) crystal form either an ordered or diffuse counterionic layer. Finally, the surface diffraction methods provide data on transfer of structural information from 2D clusters to 3D single crystals, which had been successfully accomplished by epitaxiallike crystallization both in organic and inorganic crystals.

Different growth rates on the opposite hemihedral faces of polar, platelike crystals of N-n-octyl-D-gluconamide were observed. One face is hydrophobic and the other hydrophilic, in keeping with contact angles of various solvents on these faces which were measured. It was found that the different growth rates can be explained by the hydrophilicity and hydrophobicity of the crystal surfaces.

The contact angle of a crystal face affords information about the absolute configuration of the molecules forming the crystal. This could be demonstrated with the alkylgluconamides 1, which crystallize with the molecules arranged in layers. The angle of contact at the face consisting of the chainend alkyls is 7587°, while at the oppositely disposed face consisting of the CH₂OH groups it is 4456°C. (Figure Presented.)

Two novel methodologies for the design of solid materials with poar axes by a kinetic controlled process are described. In the first approach we demonstrate that amphiphilic molecules bearing two amide groups along the hydrocarbon chain invariably deposite to yield Z-type Langmuir-Blodgett films. Attachment of hyperpolarizable molecules to such hydrocarbon chains resulted in the formation of films displaying frequency doubling. In the second methodology, crystallographic information has been used for the design of polymeric crystallization inhibitors of a stable non-polar polymorph of PAN [N-(2-acetamido-4-nitro-phenyl)- pyrrolidene]. As predicted, addition of minute amounts of polymer 15 to a supersaturated solution of PAN results in the precipitation of the metastable polar form which displays second harmonic generation.

Nucleation, growth, and dissolution of crystals have been studied by stereochemical approach involving molecular recognition at interfaces. A methodology is described for using "tailor-made" additives designed to interact stereospecifically with crystal surfaces during growth and dissolution. This procedure was instrumental in controlling crystal morphology and in revising the concept of the structure and symmetry of solid solutions. Consequently, it was applied to the transformation of centrosymmetric single crystals into solid solutions with polar arrangement displaying second-harmonic generation and to the performance of asymmetric synthesis of guest molecules inside centrosymmetric host crystals. The method has led to a discovery of a new "relay" mechanism explaining the effect of solvent on crystal growth. Finally, it allowed for the design of auxiliary molecules that act as promoters or inhibitors of crystal nucleation that can be used to resolve enantiomers and crystallize desired polymorphs.

Monolayers of aliphatic long-chain alcohols induced nucleation of ice at temperatures approaching 0°C, in contrast with water-soluble alcohols, which are effective antifreeze agents. The corresponding fatty acids, or alcohols with bulky hydrophobic groups, induce freezing at temperatures as much as 12°C lower. The freezing point induced by the amphiphilic alcohols was sensitive not only to surface area per molecule but, for the aliphatic series (C_nH_{2n + 1}OH), to chain length and parity. The freezing point for chains with n odd reached an asymptotic temperature of 0°C for an upper value of n = 31; for n even the freezing point reached a plateau of-8°C for n in the upper range of 22 to 30. The higher freezing point induced by the aliphatic alcohols is due to formation of ordered clusters in the uncompressed state as detected by grazing incidence synchrotron x-ray diffraction measurements. The diffraction data indicate a close lattice match with the ab layer of hexagonal ice.

A new series of amphiphilic molecules bearing two amide groups along the hydrocarbon chain form head-to-tail Z-type (polar) multilayers by the Langmuir-Blodgett (LB) technique, in contrast with the common amphiphiles that tend to deposit in the head-to-head, tail-to-tail Y-type fashion. Molecules with one amide group along the chain form Y-type or Z-type structures, depending on the location of the amide along the chain. p-Nitroaniline or merocyanine groups could be aligned in a polar sense, by attaching them covalently to such amphiphiles, to yield multilayers displaying second-harmonic generation (SHG). These films were characterized by ellipsometric, X-ray diffraction, IR, UV, and SHG measurements. The Z-type deposition correlates with the observed low water contact angles of the films, indicating formation of porous structures in which water may penetrate. This behavior is rationalized in terms of the hydrophilic nature of the amide groups that retain water by hydrogen bonding. In keeping with this mechanism, it was anticipated that amphiphiles bearing other polar groups, such as hydroxyls along the hydrocarbon chain, also form Z-type LB films.

In recent studies we have reported that the insertion of one, or preferably, two amide groups in the hydrocarbon chain of amphiphilic molecules yields porous monolayers which deposit in a genuine Z-type mode. In this paper, we extend our studies to amphiphiles with an amide group and a polymerizable diacetylene function in the chain. Monolayers of monomers and polymers of 10,12-non-acosadiynoyl-S-lysine (1) and 10,12-nonacosadiynoyl-S-ornithine (2) were deposited in a Z-type mode. The differences in the photopolymerization of these films seem to depend on the odd or even location of the amide group along the chain with respect to the headgroup. These Langmuir-Blodgett (LB) films were characterized by UV-visible and Fourier transform (FT) IR (reflection-absorption mode) spectroscopies and by low-angle X-ray diffraction measurements.

A network of hydrogen bonds determines the structure of the complex A of nylon66 and perfluoroglutaric acid, HO₂C(CF₂)₃CO₂H. This explains why shorter or longer dicarboxylic acids do not form complexes with nylon66. The nylon partial structure differs from the structure of pure nylon not in the CC bond lengths but rather in the CCC angles, which result in a longer b axis. Complexes of type A are unusual, because they consist of a molecular mixture of otherwise immiscible hydrocarbons and fluorinated hydrocarbons. (Figure Presented.)

Controlled reduction in crystal symmetry has been accomplished and exploited to perform an absolute asymmetric photoreaction. The principle is based on selective introduction of a guest molecule into a centrosymmetric host structure, thus reducing the symmetry of the mixed crystal. Crystallization of (E)-cinnamamide (space group P2₁/c) in the presence of (E)-cinnamic acid results in a mixed crystal composed of two enantiomorphous halves each containing 0.5-1.0% of the acid. The replacement of N-HO hydrogen bonds between host molecules by OO lone-pair repulsion between host and guest at the chiral surfaces of the growing crystal is responsible for the stereoselective occlusion of the guest and the reduction in symmetry. Irradiation of each half separately yielded the optically active cyclobutane dimer la or lb in excess, with an enantiomeric yield in the range of 40-60%, varying from one single crystal to another. The absolute configuration of the chiral dimer la formed in excess at the +b pole (1R,2R,3R,4R) was independently assigned by the Bijvoet method, NMR, and crystal-etching experiments and is in agreement with our proposed mechanism of molecular recognition.

We have demonstrated, for the first time by diffraction methods, that a solid solution composed of host and guest molecules can exhibit a crystal symmetry lower than that of the host. The study proves that the symmetry of a solid solution is dependent not only upon the host crystal structure and the guest molecular structure but also upon the surface structure and symmetry of the host crystal. The crystal structures of (S)-asparagine monohydrate [D₂NCOCH₂CH(ND₃)CO₂.D₂O] and of the solid solution (0.848:0.152) (S)-asparagine/(S)-aspartic acid [DO₂CCD₂CD(ND₃)CO2] monohydrate were refined by using neutron diffraction data obtained at 15 K. The space group of the pure host crystal is P2₁2₁2₁(Z = 4), whereas that of the host/guest crystal is monoclinic P12₁1 with two molecular sites per asymmetric unit. The ratios of guest/host occupancies of the two independent sites are 0.173:0.827 and 0.132:0.868. The reduction in symmetry is in accordance with the preferred adsorption of guest aspartic acid on the (010) crystal face at half of the orthorhombic, symmetry-related surface sites. Aspartic acid mimics, at the preferred (010) surface sites, molecular asparagine, participating in all hydrogen bonds. At the less-favored (010) surface sites a \u201cnormal\u201d N-H.O(host) hydrogen bond is replaced by O(hydroxyl).O(host) repulsion between lone-pair electrons.

We have determined the packing arrangement of a floating monolayer of palmitoyl-(R)-lysine at the air-water interface by grazing incidence X-ray diffraction and reflection measurements. These techniques utilize the unique properties of synchrotron radiation: high intensity within a small natural collimation. In the grazing angle diffraction experiment two peaks were detected in the "twodimensional powder" pattern from a monolayer of palmitoyl-(R)-lysine. Their widths indicated coherence lengths of 500 J~. The positions and intensities of these peaks allowed us to choose between various models and to determine the monolayer structure. The packing arrangement of the Qt-amino acid headgroups in the model proved to be very similar to that found in the crystal structures of the 0t form of glycine and several hydrophobic at-amino acids, thus providing a simple explanation for the oriented crystallization of 0t-glycine at monolayer-solution interfaces. The tilt of the molecule calculated from the model is consistent with the results from reflectivity measurements and X-ray powder diffraction data of the crystalline powder material. Reflectivity measurements indicate that at surface pressures as high as 30 mN m- 1 the monolayer covers only about 90% of the surface. Reflectivity measurements of the monolayer over water and over solutions of 29/o (S)-glutamine showed significant differences, indicating binding of the solute molecules to the monolayer.

A measurement and interpretation on a molecular level of a phase transition in an ordered Langmuir monolayer is reported. The diagram of surface pressure (π) versus molecular area of a monolayer of chiral (S)-[CF3-(CF2)9-(CH2)2-OCO-CH2-CH (NH3+)CO2-] over water shows a change in slope at about πs= 25 millinewtons per meter. Grazing-incidence x-ray diffraction and specular reflectivity measurements indicate a solid-solid phase transition at πs. The diffraction pattren at low pressures reveals two diffraction peaks of equal intensities, with lattice spacings d of 5.11 and 5.00 angstroms; these coalesce for π ≥πs. Structural models that fit the diffraction data show that at π> πs the molecules pack in a two-dimensional crystal with the molecules aligned vertically. At π

Recently it has been demonstrated that a compressed monolayer of palmitoyl-(R)-lysine (Fig. 1) on the surface of water induces the orientated growth of α-glyeine crystals. This effect was inter-preted to be a structural match between the monolayer and the α-glycine. To test this hypothesis we undertook to determine the packing arrangement of the monolayer by grazing incidence X-ray diffraction and reflection. These techniques use the unique proper-ties of synchrotron radiation: high intensity within a small natural collimation. In the diffraction experiment two peaks were detect-able in the two-dimensional powder pattern from a monolayer of palmitoyl-(R)-lysine. The positions and intensities of these peaks allowed us to choose between various models and determine the monolayer structure. This is the first time that the crystal structure of a compressed surfactant monolayer at the airwater interface has been determined. The same techniques could be used for structural characterization of other monolayers of interest in fields as diverse as biological membranes and optical second harmonic generation. The packing arrangement of the α-amino acid head groups in the model proved to be very similar to that found in the crystal structures of α-glycine and several hydrophobic α-amino acids.

The structures of the partially reacted crystals of the two complexes (5:2) deoxycholic acid (DCA)-acetophenone and (8:3) DCA-p-fluoroacetophenone were determined by low-temperature (-170 °C) X-ray diffraction. the structure analyses indicated that both independent guest acetophenone molecules G and G in DCA-acetophenone react and that in DCA-p-fluoroacetophenone the guest molecule G reacts whereas the other guest molecule G remains unreacted because of packing of G and G molecules along the channel. the observed guest photoconversion in DCA-acetophenone is 40%; the maximum value according to packing considerations is 50%. In DCA-p-fluoroacetophenone the observed guest photoconversion is 35%, very close to the maximum theoretical yield of 33% based on packing considerations. the analysis demonstrated that during the course of photoconversion there is minimal motion of the (guest) phenyl ring, pronounced rotation of the acetyl group about the exocyclic C-C bond, and displacement of unreacted and reacted molecules. Atom-atom potential energy calculations showed that in DCA-acetophenone a guest ketyl radical with a pyramidal geometry may rotate by a full 180° without inducing prohibitively short intermolecular contacts.

A number of possible model systems for the spontaneous generation and amplification of net chirality in chemical systems by the process of crystallization are presented. In one of these a chiral resolved product (S') [or (R') generated from crystals of a multimolecular complex {S_n} or {R_n}, forms by ligand exchange diastereomeric complexes (S_n-1 S') and (R_n-1 S') which act as growth inhibitors of the parent conglomerate crystals, but at different extents. The Nickel complex of α-amino caprolactam (ACL) grown in ethanol, in basic conditions, has been investigated as an appropriate system for such a model. Kinetic, structural and morphological studies shed light on the mechanism of the asymmetric induction and demonstrated the feasibility of a complete cycle of generation and amplification of net chirality in this chemical system or others of the same type.

Photochemical reactions in crystals proceed under control of the structure, including absolute configuration, of the bulk, unless preceeded by energy transfer, in which case defects may be important. The reaction may be followed by phase separation. Two-phase systems allow wider scope for reactant selection. The presence during growth of additives, matched stereochemically to the crystal, modifies habit and growth-rate, with far-reaching consequences. Some partially ordered systems are considered.

Various properties of polar crystals, in particular the effect of solvent on their growth, are directly related to the absolute structure of the crystal. The absolute structures of polar crystals composed of achiral molecules or racenic mixtures were assigned by three independent methods involving growth and dissolution in the presence of tailor made additives: Inhibition of crystal growth, anisotropic distribution of the occluded additive, and formation of etch pits on partial dissolution of the crystal. The method has been applied to crystals of α-resorcinol, (R, S) alanine and γ-glycine, each of which exhibits oxygen-rich and hydrogen-rich faces at the opposite ends of polar axes. All three crystals were found to grow almost unidirectionally from water at the oxygen-rich end of the crystal. The results are analysed in terms of solvent-surface interactions.

Deoxycholic acid (DCA) forms channel inclusion complexes with acetone (host-guest molar ratio 5:3), diethyl ketone (2:1), and ethyl methyl ketone (2:1). UV irradiation of these three complexes led to stereospecific photoaddition of the guests at sites [C5, C6_eq, C6_ax], C6_eqand [C6_eq, C5] of the host, respectively. Crystal structures of DCA-acetone and DCA-ethyl methyl ketone at temperatures of 103 K were determined and of DCA-diethyl ketone at 293 K. The host structures are isomorphous; they form hydrogen-bonded bilayers which are juxtaposed by hydrophobic contacts to form inclusion channels delineated by four walls. The occluded ketones are sandwiched between the wide walls of the channel comprising the steroid rings A and B. The regio-and stereospecificity of these reactions are explained on topochemical grounds. The 3:1 complex of DCA-methyl pentyl ketone is very similar to that of DCA-ethyl methyl ketone. Photoirradiation leads to cleavage of the ketone, yielding acetone which subsequently adds to DCA at site C5 and C6. A different channel motif was engineered in which cyclohexanone was sandwiched between rings D and the steroid side chains, leading to photoaddition to site C16 of ring D. The 1:1 complex of (APA) apocholic acid-acetone is light stable. The X-ray structure analysis indicates a similar host bilayer structure as DCA. The acetone molecules are stacked up the channel axis, unlike in DCA-acetone, and are arranged such that the ketone C'=0' bond tends to be parallel to the nearest C-H of the steroid wall. According to this analysis the maximal distances between the ketone C'=0' group and the potentially reactive steroid C-H bond are 3.5 A for OH and 4.2 A for C'. C. The angle between the planar guest ketone group and the potentially reactive C-H bond of the host steroid was found to vary over a wide range from about 50° to 90°.

The stereoselective interactions in aqueous solution between the crystal faces of centrosymmetric (R,S) serine 1 and additives resolved and racemic threonine 2 and allothreonine 3 were studied by four independent techniques: change in crystal habit on growth, anisotropic distribution of occluded additive during the crystal growth, etch pit formation on partial dissolution and atomatom potential energy calculations. The effects of the two diastereomers 2 and 3 are radically different due to differences in adsorption: threonine is adsorbed on the {011} crystal faces; the (R) enantiomer is adsorbed at, and eventually occluded through the (011) and (011) crystal faces replacing an (R) serine molecule. By symmetry, (S) threonine is adsorbed and occluded through the enantiotopic (011) and (011) faces replacing (S) serine. In contrast, (R) and (S) allothreonine are both adsorbed primarily at the (100) and (100) faces. The results indicate that the serine moiety of adsorbed threonine and allothreonine assume the same conformation and position as the substrate molecule. The additive is adsorbed only at specific sites such that the C_βCH₃ groups emerge from the crystal surface. The observed effects lead in the case of threonine, but not allothreonine, to the assignment of its absolute configuration.

One enantiomer of an initially racemic mixture of α-amino acids can be preferentially removed from solution by selective incorporation into the opposite enantiotopic faces of growing centrosymmetric crystals of the α-form of glycine^1,16. We report here that oriented growth of crystals of the α form of glycine has been achieved under chiral Langmuir monolayers comprising amphiphilic α-amino acids, by virtue of a structural match between the monolayer and the ac surface layer of the attached growing glycine crystals. Such monolayers of α-amino acid of R configuration, containing long hydrocarbon chains, induce glycine to crystallize with its (010) face attached to the monolayer, and by symmetry the corresponding S amino-acid monolayers induce attachment of the (0&1macr;0) face of glycine. Replacement of the hydrocarbon by a fluorocarbon chain induces analogous crystallizations, albeit, with only a partial degree of orientation, whereas monolayers of a resolved amino acid bearing a cholestanoyl moiety do not promote crystallization of glycine. Monolayers of the R, S-amino acids induce attachment of both (010) and (0&1macr;0) faces of glycine. These results on oriented crystal growth provide a new route for efficient amplification of optical activity of amino acids present in solution, through the enantioselective occlusion into the growing crystals of glycine¹ at water-air interfaces covered by a monolayer.

A new general and efficient method for kinetic resolution of racemic conglomerates by crystallization in the presence of "tailor-made" additives is described. The process is explained in terms of stereoselective adsorption of the resolved additive at the surface of the growing crystals of the enantiomer of the same absolute configuration, resulting in a drastic decrease in their rate of growth and thus allowing preferential crystallization of the opposite enantiomer ("rule of reversal"). Some empirical r olutions reported in the literature are rationalized through this mechanism, and appropriate additives for the resolution of new systems are designed and successfully applied. The crystallization of the conglomerates (R,S)-glutarr1ic acid hydrochloride (GluHCl), (R,S)-threonine (Thr), (R,S)-(p-hydroxyphenyl)glycine p-toluenesulfonate (pHpgpTs)J and (R ,S )-aspa ragine hydrate (AsnH2O) in the presence of other amino acids, used as additives, has been studied in particular. It is demonstrated that the additives are occluded in the bulk of the homochiral crystal in typical amounts of 0.5-1.5%, while they are not found in the bulk of the crystals of the antipode. The possible role of the additives in nucleation and dissolution of the affected crystals is considered. A new method for the assignment of absolute configuration of chiral molecules is proposed.

Monomeric dienes 17, which pack in chiral crystal structures and yield upon irradiation chiral cyclobutane dimers, trimers, and oligomers, have been crystallized in the presence of small amounts of their photoproducts (\u201cimpurities\u201d). An efficient asymmetric induction was observed in these crystallizations; the absolute configuration of the phase precipitating in excess is always found to be opposite to that of the crystalline phase from which the impurity was generated. A mechanism is proposed in which small amounts (∼1%) of the chiral additives are stereospecifically adsorbed onto the growing sites of the stereochemically similar crystal, thereby delaying its growth. Experiments yielding evidence in support of this mechanism are presented. Possible applications of the results of this study to the optical resolution of conglomerates in general in the presence of \u201ctailor-made\u201d impurities are discussed.

A method is described for direct determination of absolute configuration of chiral polar crystals, based on changes in crystal habit induced by tailor-made impurities. The method embodies the assignment of the direction of the chiral substrate molecule with respect to the crystal polar axis based on differences in the hemihedral faces of the substrate crystals as grown from solution in the presence and absence of impurities. The molecular packing requirements and the choice of impurities for application of this method in lysine and trans-cinnamoyl alanine are outlined.

An \u201cabsolute asymmetric synthesis\u201d with quantitative enantiomeric yield, via the process of crystallization of a nonchiral compound in a chiral crystal followed by a topochemical photoreaction, has been successfully executed. The needed crystalline chiral phases, composed of unsymmetrically disubstituted dienes and with the two different double bonds correctly juxtaposed for asymmetric (2_π + 2_π) photodimerization and photopolymerization along a translational axis, were designed. The starting point for this matrix engineering was the crystal structure of the chiral monomer 1. After inspection of the shortest contacts made by the chiral sec-butyl group inside the crystal, we examined some hypothetical transfers of methyls to and from this group, with the nearest neighboring molecules; such transfers might generate phases isomorphous to 1 but composed of achiral monomers. Four systems were considered promising candidates, namely the 1:1 mixture of monomers 3 and 4 and monomers 8, 9, and 11. Three of these behave in the predicted way. Large single crystals of achiral monomer 9 were grown and irradiated, yielding, in a number of independent experiments, dimers and oligomers of either chirality, with a quantitative enantiomeric yield within the limits of experimental error.

Experiments are described in which enantiomerically pure dimers, trimers and oligomers, generated from non chiral monomers by crystallization and topochemical reaction in suitably designed chiral crystals, induce preferential crystallization of the sarent monomer in the enantiomorphous chiral phase of opposite absolutute configuration. (We coin the term "inversion rule" for this effect). A general mechanism of amplification of optical activity by crystallization is proposed on the basis of these results, involving selective adsorption of resolved impurities on the surface of chiral crystals of similar stereochemistry, resulting in a decrease of the growth rate of the affected enantiomer and consequent preferential crystallization of the antipode. The implications of this mechanism to the generation and amplification of chiralily in a closed system are discussed.

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An \u201cabsolute\u201d asymmetric synthesis of chiral dimers and polymers of variable optical yield and an asymmetric synthesis with quantitative enantiomeric yield starting from a monomer of low optical purity are described. Irradiation of polycrystalline ethyl 2-cyano-3-(p-sec-butyl-3-'(E)-propenoate)phenyl(E)-propenoate (1) of 60% optical purity or above leads to the formation of chiral dimers and oligomers with quantitative enantiomeric yield. Carefully crystallized samples of 1 of 22-60% optical purity lead to enantiomeric excesses of 90% or above. Racemic 1 crystallizes from the melt either in the form of a stable eutectic mixture or in the form of an isomorphous, chiral, metastable phase of different microcomposition. A method for the characterization of the two phases, based on photodimerization and NMR analysis of the diastereomeric dimers, is described. Irradiation of samples of the chiral metastable phase with one enantiomorphous crystal form in excess leads to an \u201cabsolute\u201d asymmetric synthesis with variable optical yield, of both signs. Possible routes to the achievement of an \u201cabsolute\u201d asymmetric synthesis with quantitative enantiomeric yield, in systems related to 1, are discussed.

In recent years there has been increased interest in organic chemistry to mimic the enzymatic reactions of nature in order to increase the power of synthetic methods1. Molecular crystals are very convenient vehicles for the performance of such reactions, since in them as in an enzyme, the geometrical contacts between reacting centers of the rigid molecules are strictly defined by the packing of the crystal.

The stereocourse of the reaction of solid dihalogenoadipodinitriles with gaseous ammonia has been investigated in terms of the conformation of the reacting molecules in the crystal; under the heterogeneous conditions of the reaction, in certain systems, an equilibrium between different rotamers occurs before an anti-type elimination takes place.

Solid-state thermolysis at 90°C or photolysis at ambient temperature of the molecular complex of deoxycholic acid with di-t-butyl diperoxycarbonate leads to a one-step regiospecific and stereospecific hydroxylation at position 5 of the acid.

Solid dimethyl and dibenzyl esters of meso-β,β-dichloro- and meso-β,β-dibromo-adipates react quantitatively with gaseous dry ammonia, methylamine, and dimethylamine, yielding stereospecifically the corresponding diesters of trans,trans-hexa-2,4-dienedioic acid. When the same reactants were combined in ethanol or dimethylformamide solutions, a mixture of 2,4-trans,cis- and trans,trans-diesters and -diamides was obtained. Possible routes for the reaction are discussed.