Probing Phase Transitions in Organic Crystals Using Atomistic MD Simulations

Abstract

A profound understanding of the physicochemical properties of organic crystals is crucial for topics from material science to drug discovery. Using molecular dynamics (MD) simulations with a sufficiently accurate force field, microscopic insight into structure and dynamics can be obtained of materials, including liquids and biomolecules. They are a valuable complement to experimental investigations that are used routinely in drug design, but not very often for studies of organic crystals. Indeed, the often delicate interactions in organic crystals act as a sensitive probe to investigate the accuracy of force fields. Here, we study the structural, dynamic, and thermodynamic properties of 30 organic crystals using the popular general AMBER force field (GAFF). In particular, we investigate both solid-solid and solid-liquid phase transitions. Melting points were determined using extensive solid-liquid coexistence simulations. For many compounds, we detect a phase transition from an ordered to a plastic crystal in the simulations. Based on the translational and rotational dynamics of the compounds, we can rationalize the properties of the plastic crystal phase. MD simulations can therefore help to answer the important question of whether or not organic crystals have a plastic crystal phase, and if so, what are the underlying factors in the molecular structure determining that.