Soft anions promote protein folding through binding backbone CH and CH2 groups.

The solubility of hydrophobic molecules in water is sensitive to salt addition in an ion‐specific manner. Such “salting‐out” and “salting‐in” properties have been shown to be a major contributor to the measured ion‐specific Hofmeister effects that are observed in many biophysical phenomena. Various theoretical models have suggested a number of disparate mechanisms for salting‐out (salting‐in) of hydrophobic moieties, the most popular of which include preferential interaction, water‐mediated association, and electrostriction models. However, a complete molecular level description of this ion‐specificity is not yet available. This work investigates the ion‐specific nature of hydrophobic solvation by studying how sodium and chloride salts affect the thermodynamics of 1,2‐hexanediol micellization. The results of this study are analyzed in terms of scaled‐particle theory and we show that salt addition can affect hydrophobic solvation in two modalities: salt addition changes the cavitation free energy; salt addition also influences the solvent‐solute interaction energy by changing the hydration of the hydrophobic solute. These two effects are salt specific in nature and we suggest that for small hydrophobic solutes these effects are the main cause of salt‐specific Hofmeister effects on their solubility.

The Cover Feature depicts the effects of salt addition on hydrophobic solvation as represented by the micellization of 1,2‐hexanediol amphiphile. The addition of salt affects the free energy of cavitation and the packing density of the aqueous solvent. The net result of these two effects is a decrease in the solubility of the hydrophobic tail of 1,2‐hexanediol. This is why the micellization of 1,2‐hexanediol is enhanced in saline solutions relative to pure water. More information can be found in the Article by O A. Francisco et al. on page 484 in Issue 6, 2020 (DOI: 10.1002/cphc.201901000).