Enthalpy-Entropy Compensation

Enthalpy-Entropy Compensation (EEC) is observed in many unrelated domains. It appears as a strong correlation of the variations {Delta}{Delta}H and {Delta}{Delta}S of enthalpy and entropy resulting from experiments performed either at different temperatures on a given system (e.g. the binding of a ligand on a macromolecule), or at the same temperature T on related systems (e.g. the binding of related ligands on a macromolecule). In both cases, EEC is characterized by the compensation temperatures ({Delta}{Delta}H/{Delta}{Delta}S). When a continuous variable X (e.g. X = pH) characterizes the related systems at constant temperature, {Theta}T = ({partial}{Delta}H/{partial}{Delta}S)T may be used in lieu of the ratio of finite variations and when T is variable and X constant, one may always consider {Theta}X = ({partial}{Delta}H/{partial}{Delta}S)X. Thermodynamics trivially imposes {Theta}X {equiv} T, but also {Theta}T = T +{delta} T (X, T), where the corrective term{delta} T (X, T) only depends on {Delta}G(X, T). The quest for molecular explanations of EEC is thus vain: only the value of {Theta}T deserves such explanations. This is illustrated with the denaturation of globular proteins and with the dissociation of hydrophobic peptides from a specific protein. The theoretical estimate {Theta}T = (T - T*)/Ln(T /T*) with T*[~=] 383 K being imposed by experiments, fits well experimental results. Considerations of molecular dynamics (MD) methods led to a theoretical estimate for {Theta}T when no continuous variable X exists. One might obtain better MD estimates of {Delta}H and {Delta}S of binding by imposing the correct value of {Theta}T.