A theoretical study of tautomerism of cytosine, thymine, uracil and their 1-methyl analogues in the gas and aqueous phases using AM1 and PM3

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, relative proton affinities, tautomeric equilibrium constants, dipole moments, and ionisation potentials for the tautomers of cytosine, uracil, thymine and their 1-methyl analogues have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the oxo-amino or dioxo tautomers are the most stable both in the gas and aqueous phase. The results are in good agreement with the available experimental and theoretical data. The entropy effect on the Gibbs free energy of the pyrimidine bases is very small and there is little significance for the tautomeric equilibria of pyrimidine bases. The enthalpic term is dominant also in the determination of the equilibrium constant. (C) 2000 Elsevier Science B.V. All rights reserved.