W0180

Predicting Polymorphic Crystal Structures. Mark C. Wahle, Olaf König, Gerhard E. Engel, Frank J. J. Leusen, Molecular Simulations Inc., 9685 Scranton Road, San Diego, CA 92121 USA

Polymorphism can be the source of many problems in multiple industries, including pharmaceuticals, pigments, and explosives. In crystallization processes, concentration, solvent, and impurities all play a role in the formation of multiple polymorphic forms. Different forms can possess different physicochemical properties: bioavailability, stability, color, density, morphology, and mechanical behavior. To fully understand these property differences, it is extremely important that scientists have detailed knowledge of all possible polymorphs of a given compound. Furthermore, rational control of solid-state properties and crystal engineering require knowledge of the crystal structure. [1] Single-crystal X-ray diffraction is the ideal method for solving crystal structures. However, it is often difficult to grow quality single crystals for analysis. It is also impossible to determine if crystals of all possible polymorphs have been grown experimentally. Subsequently, the ability to predict the crystal structures for different polymorphs of a given compound from the molecular structure alone is highly desirable. A multi-step process, MSI's Polymorph Predictor, has been developed for polymorph prediction of fairly rigid, non-ionic compounds consisting mostly of C, H, O, and N atoms. [2] The first step includes a Monte Carlo simulated annealing process to generate thousands of potential packing arrangements. These potential structures are then clustered into unique groups based on packing similarity. Each unique structure is subsequently minimized with respect to all degrees of freedom. Finally, each structure is ranked according to lattice energy. The resulting low-energy structures are potential polymorphs; calculated powder patterns of these structures can be compared to experimental powder data for verification. The polymorph prediction of a number of compounds will be presented to support this method.

[1] Desiraju, G. R. Science, 1997, 278, 404-405.

[2] Leusen, F. J. J. J. Cryst. Growth, 1996, 166, 900-903.