Energy Increment Method Based on Quantum Chemical Results:  A General Recipe for Approximative Prediction of Isomerization and Tautomerization Energies of Pyrimidine and Purine Nucleic Acid Bases and Related Compounds

On the basis of HF/6-31G(d,p) and MP2/6-31G(d,p) quantum chemical computations of fully optimized structures of all isomers of cytosine, isocytosine, uracil, thymine, adenine, guanine, xanthine, and many model compounds, a system of additive energy increments has been derived, from which energies of conversion of geometric isomers (conformers) and tautomers of these nucleic acid bases may be reconstructed within approximately 0.5 kcal/mol. The increments are associated with specific structural fragments perceptible in the conventional structural formula. Physically, they correspond to repulsions between H atoms of −OH, −NH2, and NH substituents and H atoms bound to C or N ring atoms and to attractions between H atoms of such substituents and sp2 lone electron pairs localized at N atoms of the ring systems or of imino substituents. Tautomerization energies associated with displacements of H atoms among ring N atoms were included in the estimation process of the increments. Keto−enol and amino−imino tautomerization energies may be estimated from total electronic energies and increments of conformer conversion energies. The estimates also approximately apply for ΔU° (0) and ΔU° (T 0) (free molecules). The extended data set allowed some global structural features of the nucleic acid bases (such as formally aromatic 6-rings), which influence certain increments specifically, to be discerned. The set of increments presented may serve as a basis of a rather general recipe for predictive estimation of conformer and tautomer conversion energies of a wide range of hydroxy- and amino-substituted aromatic nitrogen bases and of effects of geometric isomerism on energetics of intermolecular H bonding involving −OH, −NH2, and NH substituents and protonated keto groups.