Quantum-Chemical Studies on the Favored and Rare Tautomers of Neutral and Redox Adenine

Abstract

All possible twenty-three prototropic tautomers of neutral and redox adenine (nine amine and fourteen imine forms, including geometric isomerism of the exo ═NH group) were examined in vacuo {DFT(B3LYP)/6-311+G(d,p)}. The NH → NH conversions as well as those usually omitted, NH → CH and CH → CH, were considered. An interesting change of the tautomeric preference occurs when proceeding from neutral to reduced adenine. One-electron reduction favors the nonaromatic amine C8H-N10H tautomer. This tautomeric preference is similar to that (C2H) for reduced imidazole. Water molecules (PCM model) seem to not change this trend. They influence solely the relative energies. The DFT vertical detachment energy in the gas phase is positive for each tautomer, e.g., 0.03 eV for N9H-N10H and 1.84 eV for C8H-N10H. The DFT adiabatic electron affinity for the favored process, neutral N9H-N10H → reduced C8H-N10H (ground states), is equal to 0.18 eV at 0 K (ZPE included). One-electron oxidation does not change the tautomeric preference in the gas phase. The aromatic amine N9H-N10H tautomer is favored for the oxidized molecule similarly as for the neutral one. The DFT adiabatic ionization potential for the favored process, neutral N9H-N10H → oxidized N9H-N10H (ground states), is equal to 8.12 eV at 0 K (ZPE included). Water molecules (PCM model) seem to influence solely the composition of the tautomeric mixture and the relative energies. They change the energies of the oxidation and reduction processes by ca. 2 eV.

DFT studies on the favored and rare tautomers of neutral and redox cytosine

“…Consequently, the geometry-based indices (HOMED6 and HOMED8) [21,52,53,58,59]. This indicates that all tautomeric conversions for cytosine (Scheme S1, Supplementary Material) are isoentropic processes in the gas phase.…”

“…Geometric and energetic consequences of prototropy have also been examined and compared to those observed earlier for 4APM and 2OHPM. For investigations, the DFT method [54] has been employed with the hybrid functional of Becke [55] and gradient correction of Lee et al (B3LYP) [56] and the 6-311?G(d,p) basis set [57] as previously described for adenine and its models [52,53,58,59]. The B3LYP functional has been recommended for charged radicals [60] and applied for the anionic states of nucleic bases [51].…”

Geometric consequences of electron delocalization for adenine tautomers in aqueous solution

“…When geometric isomerism of the imine forms is taken into account, 37 isomers are possible (Fig. S1, Supplementary material) [15]. The number of the prototropic tautomers for adenine is a consequence of the number of the labile protons (two) and conjugated tautomeric sites (ten).…”

“…Geometries of adenine isomers in their ground states were fully optimized without symmetry constraints at the DFT(B3LYP)/6-311+G(d,p) level [27–30], and next re-optimized at the PCM(water)//DFT(B3LYP)/6-311+G(d,p) level [31, 32] as previously described [15]. For all calculations, the Gaussian 03 program [33] was used.…”

“…To properly determine the distribution of π- and n-electrons for all individual tautomers of adenine, and to describe well the relation between prototropy and electron delocalization, the recently extended geometry-based harmonic oscillator model of electron delocalization (HOMED) procedure [13, 14] was applied to the geometries of the adenine isomers optimized in aqueous solution at the PCM(water)//DFT(B3LYP)/6-311+G(d,p) level [15]. The HOMED index is based on the original harmonic oscillator model of aromaticity (HOMA) idea [16, 17].…”