Molecular Scale Solvation in Complex Solutions

Complex solution environments are ubiquitous in nature. Most life science systems contain hydrated macromolecules whose solubility, function and stability are modulated by several small organic molecules or salts (cosolutes) present simultaneously. This Perspective discusses solvation of mixed cosolutes in water. Recent computer simulations and experiments have shown that nonadditive cosolute effects on the water solubility of thermoresponsive polymers and on protein stability have a common physical origin, rooted in solvent-excluded volume effects determined by mutually enhanced cosolute hydration in bulk. We discuss mixtures of weakly and strongly hydrated salts in the anionic Hofmeister series and mixtures of urea and trimethylamine N-oxide. Nonadditive phenomena in these mixtures lead to intriguing effects including consecutive polymer collapse and swelling transitions and counteraction of denaturant-induced protein unfolding. The combination of today's advanced simulation methods and spectroscopy techniques should be used to improve further the understanding of these complex aqueous solubility problems.