Cation Hydrophobicity Effects on Protein Solvation in Aqueous Ionic Liquids

This study examines the influence of cation hydrophobicity on protein solvation in aqueous solutions of Ionic Liquids. Ubiquitin solvation structures and thermodynamics in systems with 1-ethyl-3-methylimidazolium ([EMIM]+) and 1-butyl-3-methylimidazolium ([BMIM]+) are studied using molecular dynamics simulations, minimum-distance distribution functions, and the Kirkwood-Buff theory of solvation. At low concentrations, the larger alkyl chain leads to enhanced water exclusion and increased accumulation of [BMIM]+ at the protein surface relative to [EMIM]+. The preferential solvation, nevertheless, depends on the ionic liquid concentration differently for each cation. As concentrations increase, [BMIM]+ relative accumulation decreases relative to [EMIM]+. This causes a reversal of cation-protein affinities relative to water, and [EMIM]+ displays greater preferential solvation of the protein at higher concentrations. This reversal is a consequence of the saturation of the cation-specific protein surface binding sites, and the different molarities of water in the bulk solutions implied by the cation sizes. These effects are mostly independent of the anion that composes the IL.