Determination of acidity constants for weak acids and bases by isothermal titration calorimetry

The advantage of isothermal titration calorimetry (ITC) to determine the acid dissociation constant (pKa value) is the simultaneous determination of the binding constant and binding enthalpy, as well as being precise and easy to use. The pKa can be calculated from the binding constant, and the temperature dependency of the pKa can be calculated from the binding enthalpy. The use of ITC to study protonation reactions is less common compared to its more conventional use of studying macromolecules and ligands. Water will influence the equilibrium due to autoionization, meaning that both the conjugate base and acid will exist in the sample cell at the beginning of the experiment. These differences are accounted for by optimizing the theoretical model used to estimate the binding constant and binding enthalpy. Through simulations and experimental measurements, we show that ITC can be used to determine the pKa for ibuprofen, ascorbic acid, 2-morpholin-4-ylethanesulfonic acid and paracetamol. The pKa values were consistent with potentiometric or spectrophotometric determinations as well as literature values. Optimizing the theoretical model does not lead to an improved determination, so the "one set of sites" model is adequate for the determination of pKa values.