Computer simulation of cosolvent effects on hydrophobic hydration

The effects of cosolvents on the solubility and hydration of small nonpolar solutes in solution has been investigated using a combination of molecular dynamics simulation and Widom particle insertion calculations. Results were obtained for helium, neon, argon, and methane solutes in solutions of sodium chloride, ammonium sulfate, calcium chloride, ammonium acetate, tetramethylammonium chloride, guanidinium chloride, urea, and TFE. The effects of varying the cosolvent concentration was also investigated for guanidinium chloride, urea, and TFE. The calculated salting out constants were in excellent agreement with experimental data even though the solvation free energy differences were small in magnitude. Analysis of the solvation properties of the solutes in different cosolvents using a preferential binding model indicated that, for low cosolvent concentrations, the degree of preferential cosolvent binding to the solute was the dominant factor in determining the change in free energy of solvation and hence the salting out properties of the cosolvent.