(318a) All-Atom Analysis of Crystal Growth and Its Modulation By MD Simulation and Free-Energy Calculation

The crystal growth of urea is analyzed with all-atom molecular dynamics (MD) simulation for the (001) and (110) faces in contact with aqueous solutions. The local environment of a crystallizing molecule is treated in terms of the numbers of crystalline neighbors and the orientation relative to the crystal surface, and the molecular-level inhomogeneity of a growing surface is addressed by decomposing the overall rate of growth into a sum of the contributions conditioned by the local structure and orientation mode. The contrast of the growth mechanism between the (001) and (110) faces is then evidenced by the local contributions, and the roles of the outer layers of the crystal toward the liquid region are pointed out for (001). The effect of the additive species in the liquid on the crystal growth of urea is investigated with biuret, N,N-dimethylformamide (DMF), and acetone. The growth is observed to be suppressed more strongly in the order of biuret > DMF > acetone, and it is found that the ordering of suppression by the additive is common irrespective of the local environment of a crystallizing urea. This finding implies that the additive’s effect on the crystal growth can be predicted by treating the flat surface, which is a convenient system for detailed analyses at atomic resolution. The correspondence to the free energy of adsorption of the additive is then examined for the additive-induced modulation of the growth rate. It is seen that the adsorption free energy correlates to the extent of modulation of the growth rate, and the interaction components that govern the adsorption propensity are identified. The relationship the adsorption free energy and the growth-rate modulation is explored for pharmaceutically relevant compounds, furthermore.