Isothermal titration calorimetry: A thermodynamic interpretation of measurements

Highlights: ► Literature review shows that many ITC utilizations are based on empirical rules. ► A proper and rigorous thermodynamic interpretation of heats of titration is proposed. ► Heats of titration are independent of the cell type using infinitesimal titrations. ► Heats of interaction between solutes require only two different titration runs. - Abstract: Isothermal titration calorimeters have been developed and in use since the 1960s and the number of applications based on empirical rules to use them steadily increases. In this paper a rigorous study of the physical interpretation of the titration heat and the thermodynamic framework underlying isothermal titration calorimetry are proposed. For infinitesimal titrations, the titration heat is independent of the cell type employed, and the interpretation of the titration heat depends on the titrant composition and on the experiment type. Moreover, for the study of the interaction between two solutes in solution, only a combination of two experiments is necessary, and the result is interpreted as the partial enthalpy of interaction at infinite dilution of the solute contained in the titrant solution.