GENERAL THERMODYNAMIC ANALYSIS OF THE DISSOLUTION OF NONPOLAR MOLECULES INTO WATER - ORIGIN OF HYDROPHOBICITY

The Gibbs energy, enthalpy, entropy and heat capacity of transfer from the pure non-polar liquid into water are analysed in detail. It is fo und that if the combinatorial contribution to the Gibbs energy and ent ropy of transfer is subtracted from the experimental values, all non-p olar solutes in water behave in a universal manner, i.e. all of their thermodynamic transfer functions can be studied with their molecular s urface area as the only parameter. This is illustrated with the alkylb enzene series, for which experimental Gibbs energies of transfer in a wide temperature range have been obtained recently. A new interpretati on scheme for the thermodynamic transfer functions is presented and co ntrasted with that due to Privalov and Gill. It is considered that wat er molecules around the solute undergo a relaxation process which lowe rs the Gibbs energy, enthalpy and entropy of the system and is respons ible for the large heat capacity of transfer. This relaxation process is described here using a two-state model for water molecules obtained from first principles. The negative relaxation contribution to the Gi bbs energy promotes solubility, but is overcome by a large positive co ntribution arising from the creation of a cavity in water and the larg e differences between solute-solute, water-water and solute-water inte ractions. The origin of hydrophobicity lies then in the high cohesive energy of water. The proposed interpretation scheme is used to (a) pre dict the solubility of alkanes in water, (b) understand the origin of the solubility minimum appearing in aqueous solutions of non-polar sol utes, (c) rationalize the experimental finding that the enthalpy of tr ansfer becomes zero in a narrow temperature range for many non-polar s olutes, (d) discuss the significance of entropy of transfer vs. heat c apacity of transfer plots often used to understand the nature of the h ydrophobicity of non-polar solutes and proteins, and (e) account for t he expected change in sign (with temperature) of the water proton NMR chemical shifts discussed earlier in the literature.