(302a) Molecular Simulations Unravel the Dynamics of Oiling out of ?-Alanine

Crystallization is a purification process where a solute in a supersaturated environment undergoes self-assembly to form crystals. However, the degree of supersaturation may drive the solute molecules into a gel-like phase that coalesce to form crystals. In literature, this phenomenon is also known as oiling out or liquid-liquid phase separation (LLPS). The process of oiling out has been traditionally observed during the crystallization of organic molecules and biomolecules. More recently, such formation of gel-like phase has also been observed during the crystallization of Metal-organic frameworks (MOFs) as well. To obtain greater control over the process of crystallization and to obtain the desired outcome of crystallization, it is necessary to understand the molecular events which lead to oiling out of the solute molecule. In this work, we employ molecular simulations to simulate crystallization and oiling out of β-alanine molecules. Simulations uncover that supersaturation influences the configuration of solvent molecules around the solute and allows the formation of dense metastable phases before leading to crystallization. The interaction energy landscape obtained by analyzing various degrees of freedom shows that the minimum in the energy landscape lies out of the crystalline region during oiling out. Results suggest that kinetics, along with the energetics, influence the phenomenon of oiling out, and understanding solvation shell dynamics can help design better control strategies for crystallization.