Effects of ionization on stability of 1-methylcytosine — DFT and PCM studies

Abstract

Consequences of ionization were studied by quantum-chemical methods (DFT and PCM) for 1-methylcytosine (MC)—a model of the nucleobase cytosine (C) connected with sugar in DNA. For calculations, three prototropic tautomers (one amino and two imino forms) and two imino zwitterions were considered, including conformational or configurational isomerism of exo heterogroups. Ionization and interactions between neighboring groups affect intramolecular proton-transfers, geometric and thermodynamic parameters, and electron delocalization for individual isomers. We discovered that an imino isomer is present in the isomeric mixture in the highest amount for positively ionized MC. Its contribution in neutral and negatively ionized MC is considerably smaller. Acid-base parameters for selected radical ions were estimated in the gas phase and compared to those of neutral MC. Gas-phase acidity of radical cations is close to that of the conjugate acid of MC, and gas-phase basicity of radical anions is close to that of the conjugate base of MC. Various routes of amino-imino conversion between neutral and ionized isomers were considered. Energetic-barrier for intramolecular proton-transfer in MC is close to that in the parent system—formamidine.Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-016-3020-2) contains supplementary material, which is available to authorized users.

Effects of Positive and Negative Ionization on Prototropy in Pyrimidine Bases: An Unusual Case of Isocytosine

“…For the favored radical anions, the labile proton can be transferred from the exo N7 atom to endo N3 atom and vice versa in the amidine group. The Gibbs energy barriers for neutral and ionized forms of isocytosine are typical for tautomeric conversions in the amide and amidine groups (>140 kJ mol –1 ). ,− Positive ionization slightly increases the energy barrier for proton-transfer in comparison to the neutral forms. Other prototropic molecules present in environment usually participate in the intramolecular proton-transfer of tautomeric system and reduce the energy barrier. ,− …”

“…Consequently, the H-bonded adducts of iC radicals with amphiprotic compounds of similar acid–base properties confirm the proton-transfers possible in the redox nucleic acid–base pairs and their methyl derivatives, when one base is ionized by one-electron oxidation or by one-electron reduction. − The labile proton can move from radical cation to neutral base or from neutral base to radical anion, between the sites of analogous acid–base properties according to the Δ acid H /PA scale, i.e., when the energy gap for proton-transfer in ionized pairs is favorable. For example, taking into account the proton acid–base properties of the canonical neutral and radical forms of isocytosine (guanine building block) and those of 1-methylcytosine studied previously at the same DFT level, the labile proton at N3 in iC3 + • (Δ acid H = 920 kJ mol –1 ) can move to the N3 atom in neutral 1-methylcytosine (PA = 971 kJ mol –1 ), and also the labile proton at N3 in iC3 (Δ acid H = 1419 kJ mol –1 ) can move to N3 in radical anion of 1-methylcytosine (PA = 1468 kJ mol –1 ). Both proton-transfers seem to be exothermic (energetic gain ca.…”