Figure 1.

Thermodynamic diagram of the effects on the standard chemical potential of water of (i) addition of a cosolvent (μ_s) and (ii) addition of a protein surface element to pure water, μ_p, and of aqueous solutions of an inert (neutral) cosolvent (μ_sp) and of an excluded cosolvent (μ_sp^excl). (For comparison, the effect of a bound cosolvent is shown (μ_sp^bound) by the short dashed line.) The osmotic effect on water molecules on a protein surface is Δμ_p^osm = Δμ^osm. An excluded cosolvent raises the standard chemical potential by Δμ_excl. The dot–dash lines represent cosolvents with different magnitudes of exclusion. The levels (a), (b), and (c) could correspond, for example, to the changes in preferential hydrations measured in the presence of triethylene glycol, betaine, and sucrose during the specific binding of gal repressor (18).