Tautomeric equilibria of 2- and 4-thiouracil in gas phase and in solvent: A density functional study

The relative stabilities of the five favored tautomers of 2- and 4-thiouracil in gas phase and in water solution were determined by density functional theory employing the Becke, Lee, Yang, and Parr (B3LYP) exchange–correlation potential and the three 6-31G(d,p), 6-311CCG(d,p), and triple-zeta valence (TZVP) basis sets. Zero-point vibrational corrections were also computed. Bulk solvent effects were studied in the framework of the self-consistent reaction field approach by the polarizable continuum model. All calculations indicate that the most stable tautomer for both species, in the gas phase as well as in solution, has the oxo-thione form, in full agreement with the previous ab initio and experimental studies. The tautomeric stability orders obtained in the aqueous solution are sensibly different from that in the gas phase. At B3LYP/6-311CCG(d,p) level in the gas phase, the following orders of stability for 2- and 4-thiouracil tautomers were observed, respectively: S2U1 > S2U2 > S2U4 > S2U5 > S2U3 and S4U1 > S4U2 > S4U3 > S4U4 > S4U5. The corresponding trends in the aqueous phase are S2U1 > S2U3 > S2U2 > S2U5 > S2U4 and S4U1 > S4U2 > S4U3 > S4U5 > S4U4. On the basis of the computed energy differences we can hypothesize that only the oxo-thione forms of 2- and 4-thiouracil should exist in the gas phase and in water solution.