Tautomerism of 2-thioxanthine in the gas and aqueous phases using AM1 and PM3 methods

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, relative proton affinities, dipole moments and ionisation potentials for the 14 possible tautomers of 2-thioxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level, both in the gas and aqueous phases, with full geometry optimisation. The conductor-like screening model (COSMO) was employed for aqueous solution calculations. The calculations show that the two oxothione tautomers TX (1,3,7), TX (1,3,9) and the two oxothiol tautomers TX (1,7,10) and TX (1,9,10) are the predominant species at room temperature in the gas phase and aqueous solutions. But, the oxothione-N7(H) form is more stable than the oxothione-N9(H) in the gas phase while the oxothione-N9(H) form is preferred in aqueous phase. The energy difference between TX (1,3,7) and TX (1,3,9) is predicted to be significantly lower by the polar solution. The results are in good agreement with available experimental results. The entropy effect on the Gibbs free energy of the 2-thioxanthine base is very small and there is little significance for the tautomeric equilibrium of the base. The protonation of 2-thioxantbine in both phases occurs at the imidazole nitrogen (N7 or N9), and then at the pyrimidine nitrogen (N1 or N3). (C) 2001 Elsevier Science B.V. All rights reserved.