The Eggers laboratory has proposed a modification of the traditional Gibbs-free energy equation for binding equilibria that includes a term for the change in solvation energy (ΔG S ), weighted by the concentration of complex formed. This modification accounts for the water molecules released from the surface of the reactants upon binding. In the current study, this approach is applied to three experimental binding systems that differ in the degree of electrostatic contributions. The model systems include the chelation of Ca 2+ by EDTA and two host−guest reactions, the pairings of p -sulfonatocalix4arene with tetramethylammonium ion and cucurbit7uril with N-acetyl-phenylalanine-amide. Each reaction pair is examined by isothermal titration calorimetry at 25 °C in the presence of a common osmolyte, sucrose, and a common chaotrope, urea. For all pairings, the equilibrium quotient, K , is measured as a function of reactant concentration. The results demonstrate how secondary solutes influence the binding equilibrium by two distinct mechanisms, one that yields activity coefficients of nonunity and alters the observed value of ΔG° (due primarily to cosolute−reactant interactions) and one that yields a change in the solvation free energy (due to cosolute−water interactions). We conclude that urea generally weakens binding and increases the solvation free-energy penalty, whereas the effect of sucrose is dependent on the electrostatic character of the binding pair. This work suggests a pivot in the fundamental application of thermodynamics to aqueous solution chemistry and, consequently, may have broad implications for biophysical research.
Daryl K. Eggers (Sun,) studied this question.