Ca+2 and EDTA Binding Interactions: Relationship between Desolvation Energy and Equilibrium “Constant”

Desolvation energy is the difference in energy between the subpopulation of water within the solvation shells of the reactants and the subpopulation of water that is released to the bulk phase when two surfaces meet to form the product.  Generally, this term is neglected or omitted in the analysis of aqueous reaction equilibria.  In contrast, we hypothesize that the desolvation energy plays a significant role in aqueous reaction equilibria and must be taken into consideration upon analysis and application of thermodynamic equations.  To test our hypothesis, isothermal titration calorimetry was used to examine the interaction of Ca⁺² and EDTA.  This model binding reaction was examined at four concentrations and four temperatures.  The results support the idea that the equilibrium “constant” is dependent upon reactant concentrations whenever the desolvation energy is nonzero.  These data are consistent with a governing equation for the standard state free energy, first derived by our group, which includes a desolvation energy term weighted by the number of complexes formed at equilibrium in addition to the traditional term (-RTlnK).  The desolvation energy term was found to be an unfavorable, positive value for binding of Ca⁺² and EDTA, but desolvation energy may be favorable and much larger in magnitude for reactions involving macromolecules such as proteins. Implications of this work may alter past interpretations and future applications of thermodynamics in biological processes.