Enthalpy-Entropy Compensation

Enthalpy-Entropy Compensation (EEC) is observed in many unrelated domains. It appears as a strong correlation of the variations ΔΔHand ΔΔSof 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 temperatureTon related systems (e.g. the binding of related ligands on a macromolecule). In both cases, EEC is characterized by the ‘compensation temperatures’ (ΔΔH/ΔΔS). When a continuous variableX(e.g.X=pH) characterizes the related systems at constant temperature, ΘT= (∂ΔH/∂ΔS)Tmay be used in lieu of the ratio of finite variations and whenTis variable andXconstant, one may always consider ΘX= (∂ΔH/∂ΔS)X. Thermodynamics trivially imposes ΘX≡T, but also ΘT=T+δT(X, T), where the corrective termδT(X, T) only depends on ΔG(X, T). The quest for ‘molecular’ explanations of EEC is thus vain: only the value of ΘTdeserves 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 ΘT= (T−T*)/Ln(T /T*) withT*≃383Kbeing imposed by experiments, fits well experimental results. Considerations of molecular dynamics (MD) methods led to a theoretical estimate for ΘTwhen no continuous variableXexists. One might obtain better MD estimates of ΔHand ΔSof binding by imposing the correct value of ΘT.