On relation between prototropy and electron delocalization for neutral and redox adenine – DFT studies

Electron delocalization, which plays a principal role for the tautomeric adenine system, was studied for all possible major, minor, and rare tautomers of neutral, oxidized, and reduced adenine. The recently extended geometry-based HOMED (harmonic oscillator model of electron delocalization) index, which measures any type of resonance conjugation (π–π, n–π, and σ–π), was applied to the geometries of adenine isomers optimized at the DFT(B3LYP)/6-311+G(d,p) level. For neutral adenine, variations of the HOMED indices estimated for the whole tautomeric systems (eleven bonds) are almost parallel to those of the relative Gibbs energies (ΔG), which measure the thermodynamic stabilities of individual isomers. Some subtle effects, being a consequence of intramolecular interactions of neighboring groups and variability of electron delocalization for the imidazole and pyrimidine fragments, perturb this relation. One-electron oxidation has slight effect on the general HOMED/ΔG relation. The favored canonical NHNH tautomer is well delocalized for both neutral and oxidized adenine. One-electron reduction dramatically changes electron delocalization and thermodynamic stability of individual tautomers that two subfamilies can be distinguished on the HOMED vs ΔG plot, one for the NHNH tautomers and the other one for the NHCH isomers. The reduced canonical NHNH tautomer (although well delocalized) is not the favored one. The non-aromatic NHCH tautomer predominates in the tautomeric mixture, indicating that aromaticity is not the main factor that dictates the tautomeric preference for reduced adenine.