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

Abstract

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.

The influence of isolated and penta-hydrated Zn2+ on some of the intramolecular proton-transfer processes of thymine: a quantum chemical study

“…Theoretical studies of proton transfer in NA bases has been lasting for more than sixty years and various theories have already been proposed, such as semi-empirical molecular orbital theory, 29 ab initio molecular orbital theory 1,30-33 and DFT. 27,28,[34][35][36] It is expected that both MP2 and B3LYP methods would give very similar results for the geometrical and vibrational features of bases, 37 and DFT is an excellent compromise between computational cost and reasonable results. 38 Previous research works 39 employed the B3LYP/6-311++G** basis set to provide a much better energy description of the interaction between metal cations, NA bases, and micro-hydration bases.…”

“…26 Consequently, normal experimental techniques, such as ultraviolet absorption spectrometry, infrared absorption spectrometry, Raman spectrometry, nuclear magnetic resonance, and mass spectrometry, have their own limits in the investigations of proton-transfer processes in complicated systems, especially related to tautomers. 27 As an alternative strategy, quantum chemical methods such as the density functional theory (DFT) method have advantages in that they give the possibility of studying individual tautomers and intramolecular/intermolecular interactions. [24][25][26] One can also model the tautomeric process and predict the microscopic parameters for isolated, micro-solvated and macro-solvated systems.…”

Lactoperoxidase inhibition by tautomeric propylthiouracils

“…Tautomerism is one of the major reasons for occurrence of mutation in biological molecules, in which it could change the activity of tautomerized structure in comparison to the desired original structure [11]. It is widely known that the specific structure dictates the specific activity for the chemical/or medicinal compound thorough structure-activity relationship (SAR) [12].…”

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

“…For free nucleobases, uracil (U), thymine (T), cytosine (C), adenine (A), guanine (G), and for their model compounds, imidazole, purine, hydroxy- and amino-azines, the complete tautomeric mixtures in the gas phase have already been investigated [ 23 – 28 ]. One-electron loss and one-electron gain change acid-base properties of tautomeric groups, and consequently, change compositions of tautomeric mixtures and properties of nucleobases.…”

“…In this work, we chose 1-methylcytosine ( MC in Chart 1 ) for modeling some tendencies of cytosine, combined with sugar in the DNA structure, to intramolecular proton-transfers. MC is frequently chosen to understand various properties of cytosine included in nucleic acids [ 59 – 64 ], because its substitution at N1 eliminates one labile proton and reduces a large number of prototropic tautomers occurring for isolated cytosine [ 28 ] to that possible for cytosine connected with sugar. This change can induce significant differences in geometric parameters and in relative stabilities of canonical and rare forms of cytosine.…”