Desolvation Energy: A Rationale for Changes in Binding Affinity as Measured by ITC

Abstract

This study tests a new thermodynamic framework for aqueous binding equilibria that features an explicit consideration for the change in hydration that occurs when two solvated surfaces come into contact. As an outcome of this approach, the standard state free energy of binding is defined by the summation of two terms, the traditional term (-RTlnK) plus a desolvation free energy term that is weighted by the number of complexes formed at equilibrium. The governing equation suggests that the equilibrium ratio (K) is not a constant; this equation is supported firmly by results from isothermal titration calorimetry using the chelation of calcium(II) by EDTA as a model binding reaction. In addition, we demonstrate that secondary solutes can shift the equilibrium by altering the average free energy of bulk water; molar solutions of urea, sucrose, and trehalose result in significant changes in the equilibrium ratio without altering the standard state free energy, as defined by our working equation. This investigation provides a fresh approach for characterizing concentrated, nonideal solutions, as relevant for understanding the driving forces behind molecular interactions in a cell or tissue. If the desolvation equation is demonstrated to be correct for other binding reactions in general, this project could ignite a renaissance in the application of aqueous solution thermodynamics.