Molecular structures of eight kinds of 6-thiopurine tautomers were calculated by the B3LYP/6-311G^** method, both in the gas and aqueous phases, with full geometry optimization. The Onsager solvate theory model was employed for aqueous solution calculations. The structures, total energy, standard enthalpy, standard entropy and standard free energy were obtained. The calculations show that 6-thiopurine existing as the thione forms is the predominant isomer in the gas and aqueous phases. The thione-N(7)(H) isomer is more stable than the thione-N(9)(H) isomer in the gas phase whereas the thione-N(9)(H) isomer is more stable than the thione-N(7)(H) isomer in the aqueous phase. The results are in good agreement with available experimental results. The entropy effect on the Gibbs free energy of 6-thiopurine base is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of tautomeric equilibria. The free energy of solvation is well correlated with the dipole moments of 6-thiopurine tautomers.

Key words: 6-thiopurine, tautomer, DFT method, SCRF method, dipole moment