Molecular Solvation in Water−Methanol and Water−Sorbitol Mixtures: The Roles of Preferential Hydration, Hydrophobicity, and the Equation of State

Abstract

Molecular dynamics simulations of aqueous mixtures of methanol and sorbitol were performed over a wide range of binary composition, density (pressure), and temperature to study the equation of state and solvation of small apolar solutes. Experimentally, methanol is a canonical solubilizing agent for apolar solutes and a protein denaturant in mixed-aqueous solvents; sorbitol represents a canonical "salting-out" or protein-stabilizing cosolvent. The results reported here show increasing sorbitol concentration under isothermal, isobaric conditions results in monotonic increases in apolar solute excess chemical potential (mu2ex) over the range of experimentally relevant temperatures. For methanol at elevated temperatures, increasing cosolvent composition results in monotonically decreasing mu2ex. However, at lower temperatures mu2ex exhibits a maximum versus cosolvent concentration, as seen experimentally for Ar in ethanol-water solutions. Both density anomalies and hydrophobic effects--characterized by temperatures of density maxima and apolar solute solubility minima, respectively--are suppressed upon addition of either sorbitol or methanol at all temperatures and compositions simulated here. Thus, the contrasting effects of sorbitol and methanol on solute chemical potential cannot be explained by qualitative differences in their ability to enhance or suppress hydrophobic effects. Rather, we find mu2ex values across a broad range of temperatures and cosolvent composition can be quantitatively explained in terms of isobaric changes in solvent density--i.e., the equation of state--along with the corresponding packing fraction of the solvent. Analysis in terms of truncated preferential interaction parameters highlights that care must be taken in interpreting cosolvent effects on solvation in terms of local preferential hydration.