(599e) Identification of Polymorph Specific Molecular Interactions during the Process of Crystallization

Mechanism of molecular attachment during crystallization is known to be impacted based on the degree of supersaturation. Rapid crystallization at high supersaturations is known to produce metastable polymorphic forms and slow crystallization at moderate to low supersaturations produces stable forms of the molecule being crystallized. Experimental approaches of crystallization often rely on maintaining the operating conditions in the regime of desired crystal structure. However, the underlying mechanism of this phenomena has not yet been studied. In this study, Molecular Dynamics simulations were used to show that the dynamics of solvation shell around the molecule being crystallized plays a critical role in the formation of desired crystal structure and the effect of supersaturation can also be quantified in terms of activation barrier of crystallization. The identification of these dynamics further allows reducing complexity of modeling molecular interactions using stochastic simulation approaches. The specific molecular interactions during stochastic simulations can be reliably associated to a certain crystal structure to identify the nucleation pathway of the molecules to crystallize in certain structure. The multiscale approach highlights the importance of identifying molecular-scale kinetics of crystallization processes to successfully predict the outcome of crystallization.