he conformational properties of 6 possible tautomers of 5-fluorouracil or 5-chlorouracil were studied by using HF/3-21G method. On this basis, preference conformations of tautomers were calculated by the B3LYP/6-311＋G** method, both in the gas and aqueous phases, with full geometry optimization. The Onsager solution theory 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-fluorouracil and 5-chlorouracil existing as the dione forms are the predominant isomers in the gas and aqueous phases. The entropy effect on the Gibbs free energy of 5-fluorouracil and 5-chlorouracil 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 is well correlated with the dipole moments of 5-fluorouracil and 5-chlorouracil tautomers. In addition, the electronic structural parameters of 5-fluorouracil and 5-chlorouracil were compared with those of their parent uracil to obtain some valuable information.

Key words: 5-fluorouracil, 5-chlorouracil, tautomer, density functional theory method, self-consistent reaction field method, dipole moment