Computing the relative nucleation rate of phenylbutazone and sulfamerazine in various solvents

This work simulates the nucleation of sulfamerazine in acetone, methanol, or water, and phenylbutazone in diethyl ether, methanol, or acetone. A new method is developed to estimate the time of onset of nucleation from supersaturated solutions using molecular dynamics simulation and knowledge of the solubility of the solute and the density of the saturated solution. Calculations are based on the dynamics of pairs of solute molecules at extreme supersaturations instead of dynamics of molecular aggregates at practical supersaturations. First, the characteristic radial distance (CRD) specific to each solute-solvent system is identified. Next, the time evolution of the radial distribution function (RDF), g(r), at CRD is evaluated. The onset of the nucleation is taken as the time after which g(r) at the CRD remains constant. Finally, the estimated relative nucleation times are compared with those measured experimentally. The calculated and experimental nucleation times in various solvents are related linearly and by rank order. However, the ratio of the calculated to the experimental nucleation time is on the order of 10(-16) for sulfamerazine and 10(-14) for phenylbutazone. This discrepancy arises from the underlying assumptions that are necessarily imposed by the limitation in the number of atoms the computation can treat.