Calculation of aqueous dissociation constants of 1,2,4-triazole and tetrazole: A comparison of solvation models

Abstract

The aqueous acidity constants of 1,2,4-triazole and tetrazole have been calculated using quantum chemical methods with four solvation models. Gas-phase proton transfer reaction energies and enthalpies of formation were calculated at the G3 level of theory. For tetrazole, the G3 energies all differ from the experimental values by more than 10 kJ mol⁻¹, while for 1,2,4-triazole the agreement is significantly better. Solvation energies were calculated using the semi-empirical quantum mechanical method SM5.42R/A, the iterative Langevin dipole method iLD, the ab initio quantum mechanical polarisable continuum method IEF-PCM and the Poisson–Boltzmann method PB. The PB method consistently provided better agreement with experiment than the other methods when applied to the G3 energies, although the difference in pK_a was as large as 2.6 for tetrazole. The acidity constants obtained using PB and iLD solvation energies applied to the experimental gas-phase proton dissociation energies are in good agreement with experiment.