Heterogeneous Interactions Promote Crystallization and Spontaneous Resolution of Chiral Molecules

Predicting the crystallization of chiral molecules from solution is a major challenge in the chemical sciences. In this paper, we use molecular dynamics computer simulations to study the crystallization of a family of coarse-grained models of chiral molecules with a broad range of molecular shapes and interactions. Our simulations reproduce the experimental crystallization behavior of real chiral molecules, including racemic and enantiopure crystals, as well as amorphous solids. Using efficient algorithms for the packing of shapes, we enumerate millions of low-energy crystal structures for each model and analyze the thermodynamic landscape of polymorphs. In agreement with recent conjectures, our analysis shows that the ease of crystallization is largely determined by the number of competing polymorphs with low free energy. We find that this number and, hence, crystallization outcomes depend on molecular interactions in a simple way: Strongly heterogeneous interactions across molecules promote crystallization and favor the spontaneous resolution of racemic mixtures. Our results help rationalize a number of experimental observations and can provide guidance for the design of molecules and experimental conditions for desired crystallization outcomes.