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

Ewa D Raczyńska,Tomasz M Stępniewski,Katarzyna Zientara-Rytter,Mariusz Sapuła,Katarzyna Kolczyńska,Małgorzata Hallmann

doi:10.1007/s11224-015-0710-9

Ewa D Raczyńska, Tomasz M Stępniewski + Show 4 more

Open Access

https://doi.org/10.1007/s11224-015-0710-9

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Journal: Structural Chemistry	Publication Date: Dec 10, 2015
Citations: 15	License type: CC BY 4.0

Affiliation: Warsaw University of Life Sciences

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.

Highlights

It is well recognized that prototropy in nucleobases influences the structure of nucleic acids and their replication, mutation, and degradation processes [1,2,3,4,5,6,7,8,9,10,11,12,13]
Due to geometrical isomerism of the exo =NH group, two isomers are possible for the imino forms of cytosine (C5–C9), one with the imino H atom synperiplanar to the endo N3 atom (a) and the other one with this atom synperiplanar to the endo C5 atom (b)
Taking into account all type of isomerism possible for cytosine, the structures of twenty-one neutral isomers were optimized at the DFT(B3LYP)/6-311?G** level (Fig. 1)

Summary

Introduction

It is well recognized that prototropy in nucleobases influences the structure of nucleic acids and their replication, mutation, and degradation processes [1,2,3,4,5,6,7,8,9,10,11,12,13]. Labile hydrogens can move as protons between conjugated sites and change properties of nucleobases, their ability to H-bonding This phenomenon and the hypothesis of rare tautomers, suggested by Watson and Crick [2] in 1953 for DNA mutations, and later developed by Lowdin [3, 4] and advanced by Topal and Fresco [5], encouraged many chemists to theoretical and experimental studies on the structure of nucleobases in different environments. The hypothesis of rare tautomers and 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 It has been used for geometry optimalization in the G3B3 theory [61]

Methods

Results and discussion

Conclusions