Molecular aspects of glycine clustering and phase separation in an aqueous solution during anti-solvent crystallization

Abstract

The anti-solvent crystallization behavior of the glycine aqueous and ethanol system was addressed through molecular dynamics simulation of a non-equilibrium state. A rectangular simulation cell was assigned to mimic the instant of the first contact state of the aqueous phase (solvent) and ethanol (anti-solvent). Here, glycine zwitterions began to aggregate into clusters with the invasion of ethanol into the aqueous phase, caused by the dehydration and supersaturation of the area. The number and size of clusters gradually increased with the formation and collapse of the clusters with time progression as liquid structures. The cluster structure reacted to the degree of supersaturation and exhibited higher probability of structured interaction modes, especially in ethanol rich areas. Pre-determination of the crystal polymorph during liquid–liquid phase separation was suggested for this water and ethanol anti-solvent system with the glycine zwitterion as the simplest amino acid, which contained multiple interaction sites. These findings agree with the experimental results and support the precursor behavior of nucleation and mechanism in the two-step nucleation theory and liquid–liquid phase separation.