van't Hoff Based Thermodynamics

Receptor binding thermodynamics is a powerful tool to gain deep insight, at the molecular level, of the events which occur during drug-receptor interactions. This chapter deals with the use of van't Hoff analysis as a traditional method of thermodynamic studies to discover the enthalpic and entropic contributions of a drug to its receptor during binding equilibrium. A significant number of experimental studies addressed not only Gibbs energy but also enthalpy and entropy of ligand binding at different G-protein coupled receptors (GPCRs) and ligand-gated ion channels receptors (LGICRs). Here thermodynamic parameters, standard free energy (ΔG°), standard enthalpy (ΔH°), and standard entropy (ΔS°) of adenosine receptor binding equilibrium are reported, discussed, and compared with those observed for membrane receptors thermodynamically investigated. As for available thermodynamic data of GPCRs and LGICRs, they are evaluated in terms of two important physical phenomena, the thermodynamic discrimination and enthalpy-entropy compensation.