Protonation equilibria of the tryptophan metabolite 8-hydroxyquinoline-2-carboxylic acid (8-HQA) and its precursors: A potentiometric and calorimetric comparative study

Abstract

The protonation constants of quinaldic acid (QA), 8-hydroxyquinoline (8-HQ) and 8-hydroxyquinoline-2-carboxylic acid (8-HQA) were determined potentiometrically in KCl(aq) at I = 0.2 mol dm⁻³ at different temperatures (288.15 ≤ T/K ≤ 318.15). Their temperature dependence was modeled by the van’t Hoff equation, which allowed the calculation of other thermodynamic parameters, such as ΔH⁰ and ΔS⁰ . Protonation enthalpy changes were also experimentally determined by isothermal titration calorimetry (ITC) at T = 298.15 K in the same medium and ionic strength conditions. From the obtained results, it emerged that all stepwise protonation reactions for the three ligands are exothermic, with protonation constants decreasing with increasing temperature. Then, thermodynamic protonation parameters obtained by both approaches were critically analyzed and compared, evidencing that protonation enthalpy changes obtained experimentally by direct calorimetry are more accurate than those derived by the van’t Hoff equation. However, the latter approach proved useful to evidence possible variability of this thermodynamic parameter with temperature, thus allowing the eventual calculation of the corresponding ΔCₚ . Furthermore, on the basis of both the analysis of the obtained parameters and the results of detailed 1D and 2D ¹H NMR studies, it was possible to unequivocally determine the protonation sequence of the different functional groups of 8-HQA (as well as QA and 8-HQ): from basic to acidic pH, the first group to undergo protonation is the phenolate, followed by the quinolinic nitrogen and, finally, by the carboxylate.