The Polymorph Predictor was used to examine the potential for additional polymorphs of aspirin.
The crystal structure for aspirin.
Aspirin, also known as acetylsalicylic acid, has numerous pharmaceutical applications. First synthesized in 1897, aspirin is only found experimentally in one crystal structure. There were claims of additional forms in the late 1960s and early 1970s. However, those studies were not supported by sufficient physical data to prove the existence of these forms. Based on this history and the importance of this molecule, researchers at Zeneca  studied its potential for polymorphs using Accelrys' Polymorph Predictor.
Polymorph Predictor was successful in predicting the known crystal structure of aspirin, which contains a nonplanar conformer. Additional low-energy structures were also predicted that contained a planar conformer. While semiempirical and ab initio calculations indicated that the planar conformation is less stable than the nonplanar conformation, force field calculations suggested that the planar conformation is more stable.
The Zeneca researchers proposed that additional polymorphs of aspirin might be found if experimental crystallization conditions could be developed that would stabilize the planar conformation. Such ideas will help researchers in their attempts to find additional experimental forms of aspirin.
R.S. Payne, R.C. Rowe, R.J. Roberts, M.H. Charlton, R. Docherty, J. Comp. Chem., 1999, 20, 262-273