The preference conformations of 10 possible tautomers of 5-fluorocytosine were calculated by the BH-HLYP/6-311＋G** method, in both the gas and aqueous phases, with full geometry optimization. The Onsager solvation model was employed for aqueous solution calculations. The total energy, standard enthalpy, standard entropy and standard free energy were obtained. The calculations show that 5-fluorocytosine to exist as the enol-amino form is the predominant isomer in the gas phase, while the keto-amino form is the predominant isomer in the aqueous phase. The entropy effect on the Gibbs free energy of 5-fluorocytosine is very small and there is little significance for the tautomeric equilibria. The enthalpic term is dominant in the determination of tautomeric equilibria. The free energy of solvation was well correlated with the dipole moments of 5-fluorocytosine tautomers. In addition, the structure and mechanism of isomerization of 5-fluorocytosine were also studied by DFT method at BH-HLYP/6-311＋G** level.

Key words: 5-fluorocytosine, tautomerism, density functional theory method, self-consistent reaction field method, transition state