To what extent can methyl derivatives be regarded as stabilized tautomers of xanthine?

Taking xanthine (Xan) as an example, validity of an approach to experimental investigations of nucleotide bases’ tautomeric equilibrium, based on the use of methyl derivatives corresponding to their prototropic tautomers, was studied by 1H NMR in dimethylsulfoxide (DMSO) and by quantum chemical calculations at the B3LYP/6-311++G(d,p) level of theory. From 1H NMR spectra of m 7Xan, m 9Xan, Xan and m 3Xan conclusion was made that the N7H tautomeric forms of the last two compounds dominate in solution, which was supported by quantum chemical data. Calculated relative energies of the N9H tautomers of Xan and m 3Xan (8.74 and 9.57 kcal/mol, accordingly) are rather close to the m 9Xan one (9.11 kcal/mol). Nonspecific influence of DMSO modelled by the COSMO algorithm therewith reduces these values by approximately 2–3 kcal/mol. The data obtained imply that methyl derivatives are rather good models of high-energy tautomers of nucleotide bases, if their relative energies are not less than a few kcal/mol.