Pre-Nucleation Clusters Predict Crystal Structures in Models of Chiral Molecules.

ABSTRACT

Kinetics can play an important role in the crystallization of molecules and can give rise to polymorphism, the tendency of molecules to form more than one crystal structure. Current computational methods of crystal structure prediction, however, focus almost exclusively on identifying the thermodynamically stable polymorph. Kinetic factors of nucleation and growth are often neglected because the underlying microscopic processes can be complex and accurate rate calculations are numerically cumbersome. In this work, we use molecular dynamics computer simulations to study simple molecular models that reproduce the crystallization behavior of real chiral molecules, including the formation of enantiopure and racemic crystals, as well as polymorphism. A significant fraction of these molecules forms crystals that do not have the lowest free energy. We demonstrate that at high supersaturation crystal formation can be accurately predicted by considering the similarities between oligomeric species in solution and molecular motifs in the crystal structure. For the case of racemic mixtures, we even find that knowledge of crystal free energies is not necessary and kinetic considerations are sufficient to determine if the system will undergo spontaneous chiral separation. Our results suggest conceptually simple ways of improving current crystal structure prediction methods.