Evaluation of molecular crystal structures using Full Interaction Maps

Abstract

The specific crystalline form of a compound has a significant impact on its solid state properties. A key requirement for chemists developing crystalline materials is therefore to understand and evaluate the crystal form under investigation. We show here how the visualisation of molecular interaction maps within the context of a crystal structure can be used to evaluate the stability of polymorphic structures, assess multiple types of non-covalent interactions and provide a platform for crystal morphology analysis. Examples of three industrially-relevant compounds – sulfathiazole, anastrozole and cipamfylline – illustrate this well. A qualitative agreement with experimental stability data is observed for the five sulfathiazole crystal forms. The anastrozole crystal structure is demonstrated to optimise interactions to the strongest acceptor sites even though there are no conventional hydrogen-bond donors in the structure. Finally, the fastest growing plane of the needle-like morphology of cipamfylline is shown to have more H-bond donor and acceptor interactions per surface area than the slower growing planes.