Tautomerism of 6-thioxanthine in the gas and aqueous phases using AM1 and PM3 methods

Abstract

Heats of formation, entropies, Gibbs free energies, relative tautomerization energies, tautomeric equilibrium constants, relative proton affinities, dipole moments, and ionization potentials for the fourteen possible tautomers of 6-thioxanthine have been studied by using semiempirical AM1 and PM3 quantum-chemical calculations at the self-consistent field level, both in the gas and aqueous phases, with full geometry optimization. The conductor-like screening solvation model was employed for aqueous solution calculations. The calculations show that the two oxothione tautomers, TX (1,3,7) and TX (1,3,9), are the predominant species at room temperature in both phases, but the oxothione-N7(H) form is more stable than the oxothione-N9(H) form. The energy difference between TX (1,3,7) and TX (1,3,9) is predicted to be significantly lowered by the polar solution. The results are in good agreement with available experimental results. The entropy effect on the Gibbs free energy of the 6-thioxanthine base is very small and has practically no significance for the tautomeric equilibrium of the base. The enthalpic term is dominant in the determination of the equilibrium constant. The protonation of 6-thioxanthine in both phases occurs at the imidazole nitrogen (N7 or N9), then pyrimidine nitrogen (N1 or N3).