Understanding the Polymorphism of Aspirin with Electronic Calculations

This report presents electronic calculations of two aspirin polymorphs in order to understand the origin of polymorphism in aspirin crystals. Analysis of the calculated electronic structures, particularly the nuclear Fukui functions, reveals a structural tension between the carboxylic and acetyloxy groups, which may play a key role in the formation of aspirin polymorphs. Calculations of the lattice energies of the two polymorphs indicate that aspirin crystals may be enantiotropic.