Tomasz M. Stępniewski

On the Harmonic Oscillator Model of Electron Delocalization (HOMED) Index and its Application to Heteroatomic π-Electron Systems

The HOMA (Harmonic Oscillator Model of Aromaticity) index, reformulated in 1993, has been very often applied to describe π-electron delocalization for mono- and polycyclic π-electron systems. However, different measures of π-electron delocalization were employed for the CC, CX, and XY bonds, and this index seems to be inappropriate for compounds containing heteroatoms. In order to describe properly various resonance effects (σ-π hyperconjugation, n-π conjugation, π-π conjugation, and aromaticity) possible for heteroatomic π-electron systems, some modifications, based on the original HOMA idea, were proposed and tested for simple DFT structures containing C, N, and O atoms. An abbreviation HOMED was used for the modified index.

Quantum-chemical studies on the favored and rare tautomers of neutral and redox adenine.

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.

Consequence of one-electron oxidation and one-electron reduction for aniline

Quantum-chemical calculations were performed for all possible isomers of neutral aniline and its redox forms, and intramolecular proton-transfer (prototropy) accompanied by π-electron delocalization was analyzed. One-electron oxidation (PhNH2 – e → [PhNH2]+•) has no important effect on tautomeric preferences. The enamine tautomer is preferred for oxidized aniline similarly as for the neutral molecule. Dramatical changes take place when proceeding from neutral to reduced aniline. One-electron reduction (PhNH2 + e → [PhNH2]-•) favors the imine tautomer. Independently on the state of oxidation, π- and n-electrons are more delocalized for the enamine than imine tautomers. The change of the tautomeric preferences for reduced aniline may partially explain the origin of the CH tautomers for reduced nucleobases (cytosine, adenine, and guanine).

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

The complete tautomeric mixture consisting of nine prototropic tautomers has been studied in the gas phase at the DFT(B3LYP)/6-311+G(d,p) level for neutral, oxidized, and reduced cytosine. Rotational isomerism of the exo –OH group and geometrical isomerism of the exo =NH group have also been considered. Tautomeric conversions possible for cytosine have been compared with those for its structural models, 4-amino- and 2-hydroxypyrimidine. Effects of intramolecular interactions between neighboring groups for cytosine are analogous to those observed for model compounds. Although they are not very strong, they are sufficient to influence tautomeric equilibria and relative stabilities of individual tautomers. One-electron oxidation and one-electron reduction change tautomeric preferences. Tautomers that are rare forms for neutral cytosine become favored ones for oxidized and reduced cytosine. Aromaticity is not the main factor that dictates the tautomeric preferences. Stability of functional groups seems to be more important than full electron delocalization.

DFT studies on one-electron oxidation and one-electron reduction for 2- and 4-aminopyridines

Quantum-chemical calculations {DFT(B3LYP)/6-311+G(d,p)} were performed for all possible tautomers (aromatic and nonaromatic) of neutral 2- and 4-aminopyridines and their oxidized and reduced forms. One-electron oxidation has no important effect on the tautomeric preference for 2-aminopyridine. The amine tautomer is favored. However, oxidation increases the stability of the imine NH tautomer, and its contribution in the tautomeric mixture cannot be neglected. In the case of 4-aminopyridine, one-electron oxidation increases the stability of both the amine and imine NH tautomers. Consequently, they possess very close energies. As major tautomers, they dictate the composition of the tautomeric mixture. The CH tautomers may be considered as very rare forms for both neutral and oxidized aminopyridines. A reverse situation takes place for the reduced forms of aminopyridines. One-electron reduction favors the C3 atom for the labile proton for both aminopyridines. This may partially explain the origin of the CH tautomers for the anionic states of nucleobases containing the exo NH2 group.