(351aj) Para-Crystallization Behaviors in Organic Solvents

Crystallization from solution underlies myriad processes in nature and industry. Solvents crucially determine the crystal habit and solvent-surface interactions impose distinct crystal morphologies. The association of solute molecules to crystal growth sites drives away solvent associated to solute and structured in the vicinity of growth sites. Thus, insight into the solvent structure and dynamics at the crystal-solution interface is an essential prerequisite for understanding of growth mechanisms. In recent years, the crystallization of organic materials from the organic solvents has been a focus of attention as a major step in the manufacture of pharmaceuticals and fine chemicals. Despite extensive efforts, a molecular perspective of the fundamental thermodynamics and kinetics aspects of the growth mechanisms remain elusive. We employ all-atom molecular dynamics simulations and advanced sampling techniques to investigate the structure, dynamics, and energetics that govern the molecular behaviors during organic crystal growth. We address the solvent structuring at the interface, solute oligomerization in the solution and the adsorption of the solute monomers and oligomers on the crystal surface, processes that run parallel to crystallization and largely determine its rates and outcomes. We found that the weak intermolecular bonds between organic solvents and the crystal surface did not preclude the build-up of layered solvent structure along the surface. The degree of order in the solvation layer is determined by the chemical and topological features exposed on the crystal surface. A solvation layer nearest to the surface may impeded or promote the solvent and solute dynamics and the layer characteristics drive disparate growth rates on the anisotropic faces of β-hematin crystals, a central part of the survival of malaria parasites. Furthermore, despite common beliefs, a majority species of solute in the solution may or may not be the incorporating species for the crystal growth. The (010) faces of etioporphyrin crystals, an organic semiconductor, grow by direct incorporation of the dimers with dimers present in the solution as the majority component. On the other hand, the (002) face of olanzapine, an antipsychotic drug for schizophrenia, grows by the surface diffusion with incorporation of the dimers even though dimers represent a minority component in the solution. We show that growth by dimers is preferred owing to their preferential adsorption on the crystal surface, complemented by additional dimerization on the surface. These findings are crucial for molecular-level understanding of the fundamental thermodynamic and kinetic parameters of growth that guide the optimization of crystallization from the organic solvents.