Influence of Monovalent Salts on α-Glycine Crystal Growth from Aqueous Solution: Molecular Dynamics Simulations at Constant Supersaturation Conditions

Abstract

The growth of α-glycine crystals from aqueous solution is investigated at constant supersaturations by utilizing the constant chemical potential molecular dynamics method. The study considers two faces ( 010) and ( 011) that predominantly determine the α-glycine crystal morphology. The general Amber force field (GAFF) with two different charge sets derived from semi-empirical calculations using the complete neglect of differential overlap method (CNDO) and from density functional calculations using the double-numerical plus d-and p-polarization basis set (DNP) is applied to describe α-glycine. The extended simple point charge model is used to simulate water. It is observed that the GAFF/DNP set leads to a much slower integration of glycine molecules into the crystal structure than the GAFF/CNDO set. The GAFF/CNDO set, however, causes the growth even at concentrations well below the experimental solubility. For the GAFF/DNP set, the influence of potassium chloride (KCl) and sodium chloride (NaCl) on the face growth rates is investigated. The parameters recently proposed by Yagasaki et al. [J. Chem. Theory Comput. 2020, 16, 2460−2473 are used to describe salt ions, as standard GAFF parameters lead to the unexpected formation of salt clusters at a concentration lower than the experimental solubility value. According to our simulation results, both salts suppress the growth of the ( 011) and ( 010) faces. The inhibiting effect of NaCl is much stronger than that of KCl for the (011) face, while both salts have a similar inhibiting effect on the (010) face. The results are in line with the experimental observations of the impact of salt ions on the α-glycine growth rates for the (011) face reported in literature.

Non-Equilibrium Modeling of Concentration-Driven processes with Constant Chemical Potential Molecular Dynamics Simulations

“…This allowed the prediction of the equilibrium, solvent-specific crystal geometry. Recently, CμMD was used to calculate relative growth rates for the (011) and (010) faces of glycine crystals in aqueous solutions and investigate the impact of ions on the crystal morphology …”

“…Recently, CμMD was used to calculate relative growth rates for the (011) and (010) faces of glycine crystals in aqueous solutions and investigate the impact of ions on the crystal morphology. 60 CμMD was also combined with well-tempered metadynamics 61 (WTMetaD) to predict supersaturation-dependent naphthalene crystal shapes in ethanol. 62 WTMetaD enhances the sampling of crystallization/dissolution events over simulation time scales by driving the system along carefully selected reaction variables, the collective variables (CV).…”