Calorimetric determination of enthalpy changes for proton ionization of N-[2-hydroxyethyl]piperazine-N′-[2-ethane sulfonic acid] (HEPES) and N-[2-hydroxyethyl]piperazine-N′-[2-hydroxypropane sulfonic acid] (HEPPSO) in water–methanol mixtures

Enthalpies for the two proton ionizations of the biochemical buffers N-[2-hydroxyethyl]piperazine-N′-[2-ethane sulfonic acid] (HEPES) and N-[2-hydroxyethyl]piperazine-N′-[2-hydroxypropane sulfonic acid] (HEPPSO) were obtained in water–methanol mixtures with methanol mole fraction (Xm) from 0 to 0.360. With increasing methanol, the ionization enthalpy for the first proton (ΔH1) of HEPES increased steadily from 8.4 to 15.3 kJ mol−1 whereas that for HEPPSO rose to a maximum of 21.0 kJ mol−1 at Xm = 0.123 before dropping to 18.4 kJ mol−1 at Xm = 0.360. The ionization enthalpy for the second proton (ΔH2) of HEPES varied from 20.8 kJ mol−1 in water to 13.6 kJ mol−1 at Xm = 0.360 with a maximum of 24.8 kJ mol−1 at Xm = 0.194. For HEPPSO, ΔH2 increased steadily from 23.4 to 29.2 kJ mol−1. The solvent composition was selected so as to include the region of maximum structure enhancement of water by methanol. The results were interpreted in terms of solvent–solvent and solvent–solute interactions.