Free-energy simulation studies on the hydration of tetramethylurea and tetramethylthiourea

Free-energy simulations are presented calculating the difference between the hydration free energies of tetramethylurea and tetramethylthiourea. The results are combined with estimates of the free energies of evaporation (sublimation) to explain the difference in the solubilities of the two compounds. The free energy simulations used thermodynamic integration and were repeated with two parametrizations and with different polynomial paths.