Molecular Packing and Crystal Structure-Property Relationship

Crystals are beautiful! It is equally fascinating to study them. For organic crystals, we are often mesmerized by the intricacy of the rich and unpredictable – at least for now – supramolecular tessellation sustained by intermolecular forces. The subtleties in strength and directionality of the intermolecular interactions are governed by structural diversity and conformational flexibility of molecule, and are influenced by growth conditions during the self-assembly process of crystallization, dictating the polymorphic outcome of crystal structures.

Crystals are also important! Most pharmaceutical materials are crystalline and drugs are typically manufactured and formulated as crystals in final dosage forms. Physicochemical properties of crystalline materials not only affect formulation and production, but also cast a huge impact on the performance and stability of drug products. Uncontrolled and unexpected properties or behaviors sometimes lead to product failure and possible adverse effects to patients. It becomes such an important task in drug development to identify crystal forms, design suitable crystallization processes, and characterize solid-state properties for any given drug molecule.

Despite vigorous research, our understandings of crystal growth are far from being complete, and our abilities to predict and control crystal morphology and polymorphism is very limited. Clearly, to learn how organic molecules pack themselves in their respective crystal structures permits development of new theories and tools for controlling and predicting properties of organic molecules. For this effort, we have been focusing on a series of diarylamine compounds and studying their crystal structures. By synthesizing and analyzing crystal structures of chemically similar compounds, we seek the impact by subtle chemical changes on crystal packing and intermolecular interaction patterns. We have found that crystal packing is an energetic comprise between intermolecular interaction and conformational flexibility. More importantly, these two factors are mutually affected by each other. Our modeling and computational methods enable us to examine the underlying linkage between the chemistry of a molecule and the spatial arrangement in the solid state.