Quantum Mechanical Calculations for the Misincorporation of Nucleotides Opposite Mutagenic 3,N4‑Ethenocytosine

The ubiquitous nature and persistence of
exocyclic DNA adducts suggest their involvement as initiators
of carcinogenesis. We have investigated the misincorporation
properties of the exocyclic DNA adduct, 3,N4-ethenocytosine,
using DFT and DFT-D methods. Computational investigations
have been carried out by using the B3LYP, M062X, and
wB97XD methods with the 6-31+G* basis set to determine
the hydrogen bonding strengths, binding energy, and physical
parameters. The single point energy calculations have been
carried out at MP2/6-311++G** on corresponding optimized
geometries. The energies were compared among the 3,N4-
ethenocytosine adduct with DNA bases to find the most stable
conformer. The solvent phase calculations have also been carried out using the CPCM model. The computed reaction enthalpy
values provide computational insights to the earlier experimental observation in in vitro, E.coli, and mammalian cells of a high
level of substitution mutation in which C → A transversion results from εC−T pairing [εC−T3 and εC−T4] in the adduct
containing DNA sequence.