Consequences of one-electron oxidation and one-electron reduction for 4-aminopyrimidine—DFT studies

Abstract

The consequences of one-electron oxidation and one-electron reduction were studied for 4-aminopyrimidine (4APM), which displays prototropic tautomerism. Since experimental techniques are incapable of detecting less than 0.1% of minor tautomers, quantum-chemical calculations [DFT(B3LYP)/6-311+G(d,p)] were carried out for all possible tautomers of neutral 4AMP and its redox forms, 4APM (+ •) and 4APM (- •). Four tautomers were considered: one amine and three imine tautomers (two NH and one CH form). Geometric isomerism of the exo = NH group was also taken into account. One-electron oxidation (4APM - e → 4APM (+ •)) has no significant effect on the tautomeric preferences; it influences solely the composition of the tautomeric mixture. The amine tautomer is favored for both 4APM (+ •) and 4APM. An interesting change in the tautomeric preference occurs for 4APM (- •). One-electron reduction (4APM + e → 4APM (- •)) favors the C5 atom for the labile proton. The preference of the imine CH tautomer in the tautomeric mixture of 4APM (- •) may partially explain the origin of CH tautomers in nucleobases.

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

“…Indeed, the proton transfers from the N1, N3, O7, or N8 atom to the C5 atom are very unfavorable processes, and all CH isomers can be neglected for neutral cytosine. Analogous conclusions have been derived for model compounds, 4APM [52] and 2OHPM [53], using the same level of theory. The CH tautomers (4APM4 and 2OHPM4) can be neglected for neutral 4APM and 2OHPM (DG ) 10 kcal mol -1 ).…”

“…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.…”

“…The imino OH-NH forms (DG ) 10 kcal mol -1 ) containing one labile proton at the O7 and the other one at the N1 (C5) or N3 atom (C6) can also be considered as very rare forms, and thus, they can also be neglected for neutral cytosine. They are analogous to the imino NH forms of 4APM (4APM2 and 4APM3) [52]. One exception is the imino NH-NH form with labile protons at the N1 and N3 atoms (C8), typical for the pyrimidine bases (uracil, thymine, and cytosine).…”

“…Favored and rare tautomers have solely been studied for adiabatically bound valence anions of cytosine, and the importance of the C9 tautomer discussed [51]. The CH tautomer has also been found to be favored for negatively ionized 4APM [52,53]. The hypothesis of rare tautomers and also the variability of tautomeric preferences for the adiabatically bound valence anions of cytosine and for the ionized forms of 4APM encouraged us to undertake the studies for the complete tautomeric mixture of cytosine at various oxidation states, the neutral (C), oxidized (C -e ?…”

“…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].…”