Using molecular dynamics simulations to predict the effect of temperature on aqueous solubility for aromatic compounds

Since polyphenols are highly bioactive, their separation and purification are active research topics. In the optimization of such processes, the trend of solubility at different conditions is of major interest, although obtaining experimental solubility data for polyphenols is lengthy and costly. A simple and previously explored thermodynamic integration (TI) procedure was applied to estimate the Gibbs hydration free energies at different temperatures for benzoic acid, (+)-catechin and toluene. These hydration energies were compared with experimental solubilities. An extensive test with 10 replications comprising a total of 200 molecular dynamics (MD) TI simulations was conducted. Linear trends were observed for the estimated Gibbs hydration free energy at different temperatures. Electrostatic contributions showed a strong effect for the studied polyphenols due to hydrogen bonds. Lennard-Jones (LJ) contributions to hydration free energies were small, being more significant for toluene due to cavity formation. The estimated Gibbs free energy of hydration presented an exponential trend for benzoic acid and (+)-catechin when compared to experimental solubility data. These trends were fitted to an empirical expression. To understand the physical meaning of the empirical fitting parameters, the effect of temperature in the sublimation enthalpy and in the entropy of the solid solute should be estimated. (C) 2018 Elsevier B.V. All rights reserved.