A new way of exploring packing modes and intermolecular interactions in molecular crystals is described, using Hirshfeld surfaces to partition crystal space. These molecular Hirshfeld surfaces, so named because they derive from Hirshfeld's stockholder partitioning, divide the crystal into regions where the electron distribution of a sum of spherical atoms for the molecule (the promolecule) dominates the corresponding sum over the crystal (the procrystal). These surfaces reflect intermolecular interactions in a novel visual manner, offering a previously unseen picture of molecular shape in a crystalline environment. Surface features characteristic of different types of intermolecular interactions can be identified, and such features can be revealed by colour coding distances from the surface to the nearest atom exterior or interior to the surface, or by functions of the principal surface curvatures. These simple devices provide a striking and immediate picture of the types of interactions present, and even reflect their relative strengths from molecule to molecule. A complementary two-dimensional mapping is also presented, which summarizes quantitatively the types of intermolecular contacts experienced by molecules in the bulk and presents this information in a convenient colour plot. This paper describes the use of these tools in the compilation of a pictorial glossary of intermolecular interactions, using identifiable patterns of interaction between small molecules to rationalize the often complex mix of interactions displayed by large molecules.

Novel tools for visualizing and exploring intermolecular interactions in molecular crystals.

Crystal polymorphism is encountered in all areas of research involving solid substances. Its occurrence introduces complications during manufacturing processes and adds another dimension to the complexity of designing materials with specific properties. Research on polymorphism is fraught with unique difficulties due to the subtlety of polymorphic transformations and the inadvertent formation of pseudopolymorphs. In this report, a summary of thermodynamic, kinetic and structural considerations of polymorphism is presented. A wide variety of techniques appropriate to the study of organic crystalline polymorphism and pseu-dopolymorphism is then surveyed, ranging from simple crystal density measurement to observation of polymorphic transformations using variable-temperature synchrotron X-ray diffraction methods. Application of newer methodology described in this report is yielding fresh insights into the nature of the crystallization process, holding promise for a deeper understanding of the phenomenon of polymorphism and its practical control.

Crystalline Polymorphism of Organic Compounds

Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.

THE homochirality of natural amino acids and sugars remains a puzzle for theories of the chemical origin of life1–18. In 1953 Frank7 proposed a reaction scheme by which a combination of autocatalysis and inhibition in a system of replicating chiral molecules can allow small random fluctuations in an initially racemic mixture to tip the balance to yield almost exclusively one enantiomer. Here we show experimentally that autocatalysis in a chemical reaction can indeed enhance a small initial enantiomeric excess of a chiral molecule. When a 5-pyrimidyl alkanol with a small (2%) enantiomeric excess is treated with diisopropylzinc and pyrimidine-5-car-boxaldehyde, it undergoes an autocatalytic reaction to generate more of the alkanol. Because the reaction involves a chiral catalyst generated from the initial alkanol, and because the catalytic step is enantioselective, the enantiomeric excess of the product is enhanced. This process provides a mechanism by which a small initial imbalance in chirality can become overwhelming.

Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule

4. Laplacian of the Electron Density 1592 5. AIM Properties 1593 IV. Topological Analyses of Experimental Densities 1593 A. Experimental versus Theoretical Topology 1593 1. Carbon−Carbon Bond 1593 2. Polar Bonds 1594 B. Reproducibility of the Experimental Topology 1596 1. Amino Acids and Oligopeptides 1596 2. Model Ambiguities 1598 C. Applications to Molecular Crystals 1599 1. Aromaticity in Carbon-Based Ring Systems 1599

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Chemical applications of X-ray charge-density analysis.

Toward an ab initio derivation of crystal morphology

Crystal morphology engineering by "tailor-made" inhibitors; a new probe to fine intermolecular interactions

In this paper we report the results of model calculations of the nuclear potential surfaces of van der Waals complexes consisting of large aromatic molecules and rare-gas (R) atoms. These potentials were constructed as a superposition of pairwise atom-atom potentials, the R-carbon atom pair potentials being taken from heats of adsorption of rare-gas atoms on graphite, while the R-hydrogen atom pair potentials are estimated by using empirical combination rules. The binding energies of the tetracene (T) complexes TRI are 0.7 kcal mol-' for Ne, 1.5 kcal mol-' for Ar, 1.8 kcal mol-' for Kr, and 2.2 kcal mol-' for Xe, while the equilibrium distance between R and the molecular plane of tetracene is 3.0 A for Ne, 3.45 A for Ar, 3.5 A for Kr, and 3.7 A for Xe. Low-frequency, large-amplitude motion of the R atoms parallel to the molecular plane along the long molecular axis is predicted for TR, and TR2 complexes. The potential for TRI along the long molecular axis has a symmetric double-well form, giving rise to a "tunneling-type'' motion of the R atom. For the TR2 complexes, the configuration with two R atoms located on the same side of the aromatic molecule is energetically favored over that with the two R atoms on opposite sides. No chemical isomers are expected to exist for the TRI and TR2 complexes, while for TR,, complexes with n 1 3 the possibility of the existence of two or more nearly isoenergetic isomers is indicated. The applications and implications of these data for the elucidation of some features of excited-state energetics and dynamics of such van der Waals complexes are considered. van der Waals (vdW) molecules'" are weakly bound molecular complexes held together by attractive (eg, dispersive, electrostatic, charge transfer, hydrogen bonding) interactions between closed- shell atoms or molecules. The primary characteristics of vdW molecules'd are their low (10-1000 cm-I) dissociation energies, the large length of the vdW bond, and the retention of many of the individual properties of the molecular constituents within the vdW complex. During the last few years remarkable progress was achieved in the understanding of the many facets of these interesting systems. These advances were initiated by the utili- zation of supersonic free expansion^^.^ to prepare a variety of fascinating vdW molecules, whose structure, energetics, and dy- namics were explored. The elucidation of the structure, the mapping of the potential surface, and the determination of the energetics of vdW molecules pertain to the basic understanding of intermolecular interactions in chemistry. In this context the ground-state properties of a variety of molecules, e.g., (HF)2,7 ArHF: ArHC1,9 ArHBr,l0 KrHCI," XeHC1,I2 ArCIF," ArOC- S," and the benzene dimer3 were investigated. Studies of in- tramolecular dynamics of vdW molecules in vibrationally excited or electronically vibrationally excited states provided central in- formation on reactive vibrational predissocation processes,57 this being relevant for establishing the general features of intramo- lecular vibrational energy flow in weakly coupled molecular systems. Intramolecular dynamical processes in a variety of vdW molecules, e.g., RIz (R = He, Ne, and Ar),'>'' (C12)2,18 (N2O)2,I9 (NH3)r20 and the ethylene dimer2' were recently explored both experimentally'52' and theoretically.6 The understanding of the reactive and nonreactive dynamics in vdW complexes requires detailed information on potential surfaces. The general conceptual framework advanced for the elucidation of the structural and energetic features of all these small and medium-sized vdW complexes mentioned above rests on a microscopic approach, taking advantage of the advanced techniques of molecular spec- tro~copy~~~~-" to probe the molecular equilibrium configuration, the details of nuclear motion, and the binding energies. This general approach may require some gross modifications when the structure, energies, and dynamics of very large vdW complexes will be considered. Recently, there have been experimental st~dies~~-~~ of very large vdW complexes consisting of aromatic molecules, such as anthracene, tetracene, pentacene, and ovalene

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Model Calculations of Potential Surfaces of van der Waals Complexes Containing Large Aromatic Molecules

Calculs SCM-Xα-DV: potentiels d'ionisation, energies orbitales Nature des orbitales frontieres

Nature of the frontier orbitals in phosphine, trimethylphosphine, and trifluorophosphine

Presentation d'une nouvelle methode comprenant la precipitation de cristaux centrosymetriques composes de molecules chirales ou prochirales, en presence d'additifs racemiques. Variations dans la morphologie et la segregation enantiomere des additifs a l'interieur du cristal. La configuration absolue des additifs est deduite de ces effets

Centrosymmetric crystals for the direct assignment of the absolute configuration of chiral molecules. Application to the .alpha.-amino acids by their effect on glycine crystals

Ziva Berkovitch-Yellin

Papers

Toward an ab initio derivation of crystal morphology

Crystal morphology engineering by "tailor-made" inhibitors; a new probe to fine intermolecular interactions

Model Calculations of Potential Surfaces of van der Waals Complexes Containing Large Aromatic Molecules

Nature of the frontier orbitals in phosphine, trimethylphosphine, and trifluorophosphine

Centrosymmetric crystals for the direct assignment of the absolute configuration of chiral molecules. Application to the .alpha.-amino acids by their effect on glycine crystals