Practice of polymorphism analysis with crystal calculation method

Abstract

A flexible organic molecule often crystallizes in more than one structure with characteristic packing arrangement respectively, and these crystal structures (polymorphs) show distinct physical, optical, or thermodynamic properties such as melting point, dissolution rate, morphology, and color. Therefore, analysis of polymorphism phenomenon for target molecule is quite important issue to obtain crystal with expected properties in development field of new functional materials or drugs. Recently, we have been developed CONFLEX/KESSHOU (CONFLEX/K) which can be performed analysis and prediction for conformational polymorphism of a flexible organic molecule. In this work, conformational polymorphism analysis of acetylsalicylic acid (aspirin) known as analgesic and anti-inflammatory drug was carried out using CONFLEX/K. As a consequence, aspirin conformers with s-trans carboxylic acid group generated hydrogen bonds like chain between neighboring molecules, and this chain motif was stable than dimer motif which were generated between s-cis carboxylic acid groups in experimental crystal structure.