Abstract
In this paper, the ionization constants (pKₐ) of the nitrogen-containing organic base hexamethylenetetramine in water-dioxane, water-dimethylformamide, water-ethanol, water-ace tone, and water-acetonitrile mixtures at different organic solvent contents were determined by potentiometric titration. The study was aimed at elucidating the role of solvent composition and physicochemical parameters of the medium in regulating the acid-base behavior of the compound. It has been demonstrated that both the nature of the organic component and the polarity characteristics of the mixed solvent significantly affect the character and magnitude of changes in the electron-donating ability of hexamethylenetetramine. Upon transition from pure water to aqueous-organic media, noticeable shifts in pKₐ values were observed, with ΔpKₐ reaching 0.68 units in acetonitrile-containing systems. The influence of dielectric constant, dipole moment, and specific solvation effects on the stabilization of the protonated and unprotonated forms was analyzed. In aqueous-ethanol and aqueous-dioxane mixtures, be explained by a decrease in the overall dielectric constant of the medium and the resulting weakening of electrostatic stabilization of the conjugate acid. In contrast, in aqueous-acetone and aqueous-acetonitrile systems, pKₐ remains nearly unchanged at low organic solvent con tents but increases markedly at higher concentrations, reflecting the growing contribution of specific interactions and solvation of the cation. In aqueous-dimethylformamide mixtures, a nonmonotonic dependence of pKₐ on solvent composition was observed, with a minimum at approximately 50% DMF. This behavior indicates competition between reduced bulk polarity and enhanced donor-acceptor interactions, which provide additional stabilization of the protonated species at higher DMF fractions. Overall, the results highlight the complex interplay between nonspecific electrostatic and specific solvation effects in controlling the acid-base properties of nitrogen-containing bases in mixed solvents.