The crystallographically determined bond length, valence angle, and torsion angle information in the Cambridge Structural Database (CSD) has many uses. However, accessing it by means of conventional substructure searching requires nontrivial user intervention. In consequence, these valuable data have been underutilized and have not been directly accessible to client applications. The situation has been remedied by development of a new program (Mogul) for automated retrieval of molecular geometry data from the CSD. The program uses a system of keys to encode the chemical environments of fragments (bonds, valence angles, and acyclic torsions) from CSD structures. Fragments with identical keys are deemed to be chemically identical and are grouped together, and the distribution of the appropriate geometrical parameter (bond length, valence angle, or torsion angle) is computed and stored. Use of a search tree indexed on key values, together with a novel similarity calculation, then enables the distribution matching any given query fragment (or the distributions most closely matching, if an adequate exact match is unavailable) to be found easily and with no user intervention. Validation experiments indicate that, with rare exceptions, search results afford precise and unbiased estimates of molecular geometrical preferences. Such estimates may be used, for example, to validate the geometries of libraries of modeled molecules or of newly determined crystal structures or to assist structure solution from low-resolution (e.g. powder diffraction) X-ray data.

The Cambridge crystallographic database comprises files of bibliographic, chemical connectivity and numeric structural data, for organics, organometallics and metal complexes studied by X-ray and neutron diffraction. The files, covering the literature from 1935 and maintained on a current basis, presently contain information on some 25 000 structural studies. Certain categories of information, particularly bibliographic, are disseminated in printed form via the Molecular Structures and Dimensions series. The full potential of the total database depends, however, on its response to specific user queries. The present paper describes the computer-based search and retrieval system, with special reference to question coding. The retrieved data may then be used for extensive and systematic geometric analysis, and for the visual display of crystal and molecular structures. The availability of the database is also discussed.as well as the establishment of abstracting, input and evaluation procedures. The utilization of sections of the database in the production of the reference-book series Molecular Structures and Dimensions (MSD) (Ken-nard &

DASH is a user-friendly graphical-user-interface-driven computer program for solving crystal structures from X-ray powder diffraction data, optimized for molecular structures. Algorithms for multiple peak fitting, unit-cell indexing and space-group determination are included as part of the program. Molecular models can be read in a number of formats and automatically converted to Z-matrices in which flexible torsion angles are automatically identified. Simulated annealing is used to search for the global minimum in the space that describes the agreement between observed and calculated structure factors. The simulated annealing process is very fast, which in part is due to the use of correlated integrated intensities rather than the full powder pattern. Automatic minimization of the structures obtained by simulated annealing and automatic overlay of solutions assist in assessing the reproducibility of the best solution, and therefore in determining the likelihood that the global minimum has been obtained.

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The formation of cocrystal hydrates represents a potential route to achieve molecular materials with improved properties, particularly stability under conditions of high relative humidity. We describe the use of neat and liquid-assisted grinding for screening for hydrated forms of pharmaceutical cocrystals. In the case of liquid-assisted grinding, water is present in the reaction mixture as a liquid, whereas in the case of neat grinding, it is introduced by employing crystalline hydrates as reactants. The ability to form a cocrystal hydrate by either of the two methods appears to be variable, depending on the choice of cocrystal components. Theophylline readily forms a cocrystal hydrate with citric acid. This contrasts with the behavior of caffeine, which provides only an anhydrous cocrystal ("caffeine citrate") even when both reactants are crystalline hydrates. The preference of theophylline to form a cocrystal hydrate is qualitatively explained by similarity between crystal structures of the products and reactant hydrates. Overall, liquid-assisted grinding is less sensitive to the form of the reactant (i.e., hydrate or anhydrate) than neat grinding. For that reason liquid-assisted grinding appears to be a more efficient method of screening for cocrystal hydrates, and it is also applicable to screening for hydrates of APIs.