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A new phenomenological model for interpreting the effects of solutes on biological equilibria is presented. The model attributes changes in equilibria to differences in the desolvation energy of the reacting species that, in turn, reflect changes in the free energy of the bulk water upon addition of secondary solutes. The desolvation approach differs notably from that of other solute models by treating the free energy of bulk water as a variable and by not ascribing the observed shifts in reaction equilibria to accumulation or depletion of solutes next to the surfaces of the reacting species. On the contrary, the partitioning of solutes is viewed as a manifestation of the different subpopulations of water that arise in response to the surface boundary conditions. A thermodynamic framework consistent with the proposed model is used to derive a relationship for a specific reaction, an aqueous solubility equilibrium, in two or more solutions. The resulting equation reconciles some potential issues with the transfer free energy model of Tanford. Application of the desolvation energy model to the analysis of a two-state protein folding equilibrium is discussed and contrasted to the application of two other solute models developed by Timasheff and by Parsegian. Future tabulation of solvation energies and bulk water energies may allow biophysical chemists to confirm the mechanism by which secondary solutes influence binding and conformational equilibria and may provide a common ground on which experimentalists and theoreticians can compare and evaluate their results


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