2-Thiouracil, tautomerism calculations

Quantum-mechanical studies on the tautomeric stabilities of the rare pyrimidine bases are very scarce. Tentative CNDO/2 calculations have been carried out ° on the energies of some of them. They showed that in thiouracils the most stable form in each case is form 51. In 2-thiocytosine, two forms, 52 and 55, are nearly equivalent (form 52 is more stable than 55 by 4 kcal/mole), and isothiocytosine form 56... 

The tautomeric equilibrium of 2-thiouracil in dioxane, water and acetonitrile was studied by ab initio calculations using the SCRF theory. The oxo-thione form was predicted to be predominant in all the solvents studied, but the order of tautomer stability was shown to depend on the level of theory and the dielectric constant of the solvent (00MI243). The tautomerism of protonated forms of 2-thiouracil has also been studied (00JPC(A)5122). Semiempirical AMI, PM3 and MNDO calculations of the thiol-thione tautomeric equilibrium 188c 188d predicted the mercapto form... 

Table 4 presents the proton affinities PA and deprotonation enthalpies DPE of thiouracils calculated at the B3LYP/6-31+G(d,p) computational level. Inspecting this Table, we find that first, the thio substitution of uracil systematically increases its PAs by 3-6 kcal/mol and second, it decreases the DPEs of uracil by 6-13 kcal/mol. As far as the base pair A thioU is considered, it particularly implies a lowering, on the one hand, of the potential well at the Sio atom of thiouracil corresponding to the proton transfer from the N8 atom of adenine to the Sio of thiouracil and, on the other one, a raising of the potential well at the N3 atom of thiouracil involved in the proton transfer from the N3-H bond to the Ni atom of adenine. Therefore, summarizing, the thio substitution of uracil is in a favor to the double proton transfer mechanism of the occurrence of the spontaneous point mutations proposed by Lowdin [19]. Table 4 also includes the PAs of the T2 tautomer of uracil and thiouracils. A comparison with the corresponding PAs of the parental normal nucleobases shows that their tautomerization to the T2 form is accompanied by an increase of the proton affinity by 20-23 kcal/mol. 

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