First-principle prediction of crystal habits in mixed solvents: α-glycine in methanol/water mixtures

We show, using α-glycine in an equi-volume methanol/water mixture as example, that the influence of solvent and solvent mixtures on crystal habits can be predicted by using Extended Interface Structure Analysis (EISA), a hybrid multiscale method based on molecular simulations and theoretical thermodynamic analysis of the interfacial layer. The presence of methanol is shown to lead to a well-developed (010) face compared to the less-developed one observed in aqueous solutions and to cause plate-like, bipyramidal crystals to form. The results represent the first prediction of crystal habits as a function of effects of solvent mixtures from first principles and are consistent with the experimental data available for glycine in alcohol/water mixtures. The results also illustrate that the hybrid approach presented here can efficiently incorporate interfacial molecular-scale chemical events that control crystal growth and morphology when cosolvents, impurities or additives are used, and thus the methodology can serve as a theoretical adjunct to the increasingly powerful subnanoscale experimental probes for crystal growth.