Potential polymorphs of aspirin

Aspirin is only found experimentally in one crystal structure. In this arti cle the method of Karfunkel and Gdanitz is used to predict potential polymo rphs of aspirin. The known structure, containing a nonplanar conformer is f ound, along with a number of other low energy structures, many of which are based on a planar conformer. Semiempirical and ab initio calculations show that the planar conformer is less stable than the experimentally known one . Force field calculations suggest that the planar conformer is more stable . The lattice energy of the experimentally known crystal structure is 1.4 k cal/mol lower than any of the potential crystal structures, even though the re are a number of structures with lower total (lattice + intramolecular) e nergies. Conformational maps indicate that another stable conformation occu rs within a few kilocalories per mole of the known structure. Polymorphs ar e predicted for this conformer, but it is found to pack poorly. It is propo sed that routes to producing polymorphs of aspirin might be found if consid eration is given to promoting the stability of the planar conformer with ap propriate solvents or additives. (C) 1999 John Wiley & Sons, Inc.