Intermolecular Interaction

Our research on intermolecular interaction centers on electronic structure calculation and analysis of molecular and crystal structures of organic molecules. As we know, many physicochemical properties of organic materials, including pharmaceutical compounds, are governed by intermolecular interactions. And these properties play critical roles in the stability and performance of these materials throughout manufacturing, storage, and usage processes. Even under the biological conditions, the bioperformance of drug delivery systems and dosage forms is influenced by intermolecular interactions.

In addition to general quantum mechanical methods, conceptual density functional theory (CDFT) has been heavily explored in our laboratory to analyze electronic structures. In essence, density functional theory embraces electron density as the fundamental quantity for describing atomic and molecular ground states. Several key concepts include hardness, softness, and Fukui function that can be traced back to Pearson’s HSAB (hard and soft acids and bases) principle and tightly related to Klopman’s frontier molecular orbital theory. What interests us the most is the locality of these functions so that we can utilize them to analyze local electrophilic and nucleophilic properties that determine intermolecular interactions. More importantly, these electronic properties are inherently governed by the molecular structure including conformation.

Our current focus is to apprehend how electronic structures evolve when molecules self-assemble into crystals. The change in the conformation and consequent electronic structure is believed to mutually accommodate the intermolecular interaction. The interplay between conformation and intermolecular interaction should be manifested in how molecules pack themselves in space and polymorph formation. By studying the electronic structure of a crystal through both quantum mechanical calculations and scientific visualization, we aim to untangle the web between molecule and crystal.