TAUTOMERS OF 6-THIOGUANINE - STRUCTURES AND PROPERTIES

The molecular geometries of four tautomers of 6-thioguanine (6TG) were studied using ab initio LCAO-MO method at the Hartree-Fock level. All considered species are minimum structures on the 3-21G* potential energy surface (PES) of 6TG as determined from harmonic vibrational frequencies calculations carried out at the same level. The basis set effects on the relative energies of the tautomers and their one-electron properties were studied at the HF/6-31G*, HF/6-31G**, and HF/6-311G** levels. Our best estimation of the relative stabilities of the tautomers includes electron-correlation contributions calculated at the MP2/6-31G* approximation and the zero-point energy contributions scaled by 0.9. At this level the thione N(7)H tautomer 1 is the global minimum species lying on the PES 2.3 and 12.0 kJ mol-1 below thiol N(9)H (3) and thione N(9)H (2) forms, respectively. The relatively large dipole moment predicted for the thione tautomer 2 indicates the computed tautomeric equilibria should be shifted toward this form in polar solvents. Calculated molecular parameters of 6TG tautomers are similar to those of the corresponding guanine forms. Thus suggest the possibility of an effortless replacement of guanine by its thioanalog in nucleotides, which would rationalize observed biological activity of 6TG.