Thermodynamic decomposition of hydration free energies by computer simulation: Application to amines, oxides, and sulfides

The calculation of the Gibbs free energy, enthalpy, and entropy of hydration of ammonia, methylamine, dimethylamine, trimethylamine, water, methanol, dimethyl ether, hydrogen sulfide, methanthiol, and dimethylsulfide is presented to illustrate the usefulness of the enthalpy and entropy of solvation in studying microscopic phenomena affecting the thermodynamics of the hydration of simple organic molecules. The free energy perturbation (FEP) method is used in conjunct?on with constant temperature and constant pressure molecular dynamics (MD) configurational sampling. The hydration free energies are studied as a function of the temperature in order to evaluate the hydration entropy by finite differences (FD). The TIP3P water model is used for the solvent water and revised AMBER, parameters for the solutes. Partial charges of the solutes are obtained from fitting the electrostatic potential obtained from electronic structure calculations. Discrepancies with the experiments, especially noticeable for the amines, are observed for the hydration enthalpies and entropies even in cases where the hydration free energies are in agreement with the experiments. We conclude that this molecular force field requires additional parametrization against experimental entropies and enthalpies of hydration. Other molecular force fields may also need reparametrization.