Whereas much of organic chemistry has classically dealt with the preparation and study of the properties of individual molecules, an increasingly significant portion of the activity in chemical research involves understanding and utilizing the nature of the interactions bet w e n molecules. Two representative areas of this evolution are supramolecular chemistry and molecular recognition. The interactions between molecules are governed by intermolecular forces whose energetic and geometric properties are much less well understood than those of classical chemical bonds between atoms. Among the strongest of these interactions, however, are hydrogen bonds, whose directional properties are better understood on the local level (that is, for a single hydrogen bond) than many other types of nonbonded interactions. Nevertheless, the means by which to characterize, understand, and predict the consequences of many hydrogen bonds among molecules, and the resulting formation of molecular aggregates (on the microscopic scale) or crystals (on the macroscopic scale) has remained largely enigmatic. One of the most promising systematic approaches to resolving this enigma was initially developed by the late M. C. Etter, who applied graph theory to recognize, and then utilize, patterns of hydrogen bonding for the understanding and design of molecular crystals. In working with Etter's original ideas the power and potential utility of this approach on one hand, and on the other, the need to develop and extend the initial Etter formalism was generally recognized. It with that latter purpose that we originally undertook the present review.

The pressure-induced structural transformation of CHD involves, apart from other effects, the interchange of donor and acceptor sites by the enolic H atoms in the hydrogen bonds. The structure, despite its close similarities with antiferroelectric crystals, is ordered in the high-pressure phase, also retaining its low-pressure symmetry. It is possible that the crystals have a domain structure in both low-and highpressure phases. The proposed mechanism of the transformation strongly suggests an important role of electrostatic interactions in the transformation and in the jump of the enolic H atom to its other site in the OH---O bond. This mechanism also affords an explanation of the phase transition observed in CPD and of the exceptional stability of MCPD at high pressures; however, several points still need to be confirmed and further studies are being carried out on the CHD crystals.The author is grateful to Professor Z. Katuski for encouragement, to Dr R. J. Nelmes for his invitation to use the high-pressure and X-ray facilities of the Physics Department, University of Edinburgh, to Professor M. C. Etter of the Department of Chemistry, University of Minnesota, for stimulating discussions and providing the 1,3-cyclohexanedione samples crystallized from 2-pentanone, and to Dr J. Koput (Adam Mickiewicz University) for his expertise in the MNDO calculations. This study was partly supported by the British Council and by the Polish Academy of Sciences, Project CPBP, 01.12.References ALLMANN, R. (1977 AbstractA method is presented based on graph theory for categorizing hydrogen-bond motifs in such a way that complex hydrogen-bond patterns can be disentangled, or decoded, systematically and consistently. * Alfred P. Sloan Foundation Fellow, 1989-1991 This method is based on viewing hydrogen-bond patterns topologically as if they were intertwined nets with molecules as the nodes and hydrogen bonds as the lines. Surprisingly, very few parameters are needed to define the hydrogen-bond motifs comprising these networks. The methods for making these assignments, and examples of their chemical utility are given.

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The simultaneous appearance of polymorphs of a substance has long been recognized but rarely noted or systematically studied. This phenomenon can be useful in the investigation of solid materials and in understanding the relative crystal energetics of polymorphic materials. This review covers the thermodynamic and kinetic factors that govern competitive and concomitant polymorphic crystallization. One of the many examples surveyed is a cyanine/oxonol complex, for which different relative molecular orientations in two of the many reported polymorphs are shown.

We present new facts about polymorphism based on (i) crystallographic data from the Cambridge Structural Database (CSD, a database built over 50 years of community effort), (ii) 229 solid form screens conducted at Hoffmann-La Roche and Eli Lilly and Company over the course of 8+ and 15+ years respectively and (iii) a dataset of 446 polymorphic crystals with energies and properties computed with modern DFT-d methods. We found that molecular flexibility or size has no correlation with the ability of a compound to be polymorphic. Chiral molecules, however, were found to be less prone to polymorphism than their achiral counterparts and compounds able to hydrogen bond exhibit only a slightly higher propensity to polymorphism than those which do not. Whilst the energy difference between polymorphs is usually less than 1 kcal mol(-1), conformational polymorphs are capable of differing by larger values (up to 2.5 kcal mol(-1) in our dataset). As overall statistics, we found that one in three compounds in the CSD are polymorphic whilst at least one in two compounds from the Roche and Lilly set display polymorphism with a higher estimate of up to three in four when compounds are screened intensively. Whilst the statistics provide some guidance of expectations, each compound constitutes a new challenge and prediction and realization of targeted polymorphism still remains a holy grail of materials sciences.

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