Potential polymorphs of aspirin

✍ Scribed by Payne, R. S.; Rowe, R. C.; Roberts, R. J.; Charlton, M. H.; Docherty, R.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 331 KB
• Volume: 20
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(19990130)20:2<262::aid-jcc8>3.0.co;2-8

✦ Synopsis

Aspirin is only found experimentally in one crystal structure. In this article, the method of Karfunkel and Gdanitz is used to predict potential polymorphs of aspirin. The known structure, containing a nonplanar conformer is found, 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 kcalrmol lower than any of the potential crystal structures, even though there are a Ž . number of structures with lower total lattice q intramolecular energies. Conformational maps indicate that another stable conformation occurs within a few kilocalories per mole of the known structure. Polymorphs are predicted for this conformer, but it is found to pack poorly. It is proposed that routes to producing polymorphs of aspirin might be found if consideration is given to promoting the stability of the planar conformer with appropriate solvents or additives.