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 computati ons of fully optimized structures of all isomers of cytosine, isocytosine, uracil, thymine, adenine, guanine, xanthine, and many model compounds, a sy stem of additive energy increments has been derived, from which energies of conversion of geometric isomers (conformers) and tautomers of these nuclei c acid bases may be reconstructed within approximately 0.5 kcal/mol. The in crements are associated with specific structural fragments perceptible in t he conventional structural formula. Physically, they correspond to repulsio ns 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 a nd sp(2) 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 t he increments. Keto-enol and amino-imino tautomerization energies may be es timated from total electronic energies and increments of conformer conversi on energies. The estimates also approximately apply for Delta U degrees (0) and Delta U degrees (To) (free molecules). The extended data set allowed s ome global structural features of the nucleic acid bases (such as formally aromatic 6-rings), which influence certain increments specifically, to be d iscerned. The set of increments presented may serve as a basis of a rather general recipe for predictive estimation of conformer and tautomer conversi on energies of a wide range of hydroxy- and amino-substituted aromatic nitr ogen bases and of effects of geometric isomerism on energetics of intermole cular H bending involving -OH, -NH2, and =NH substituents and protonated ke to groups.