Quasichemical analysis of the cluster-pair approximation for the thermodynamics of proton hydration.

A theoretical analysis of the cluster-pair approximation (CPA) is presented based on the quasichemical theory of solutions. The sought single-ion hydration free energy of the proton includes an interfacial potential contribution by definition. It is shown, however, that the CPA involves an extra-thermodynamic assumption that does not guarantee uniform convergence to a bulk free energy value with increasing cluster size. A numerical test of the CPA is performed using the classical polarizable AMOEBA force field and supporting quantum chemical calculations. The enthalpy and free energy differences are computed for the kosmotropic Na(+)/F(-) ion pair in water clusters of size n = 5, 25, 105. Additional calculations are performed for the chaotropic Rb(+)/I(-) ion pair. A small shift in the proton hydration free energy and a larger shift in the hydration enthalpy, relative to the CPA values, are predicted based on the n = 105 simulations. The shifts arise from a combination of sequential hydration and interfacial potential effects. The AMOEBA and quantum chemical results suggest an electrochemical surface potential of water in the range -0.4 to -0.5 V. The physical content of single-ion free energies and implications for ion-water force field development are also discussed.