Modeling H-bonding and solvent effects in the alkylation of pyrimidine bases by a prototype quinone methide: a DFT study

Nucleophilicity of NH2, N3, and O2 centers of cytosine toward a model quinone methide (o-QM) as alkylating agent has been studied using DFT computational analysis [at the B3LYP/6-311+G(d,p) level]. Specific and bulk effects of water (by C-PCM model) on the alkylation pathways have been evaluated by analyzing both unassisted and water-assisted reaction mechanisms. An ancillary water molecule, H-bonded
to the alkylating agent, may interact monofunctionally with the o-QM oxygen atom (passive mechanisms) or may participate bifunctionally in cyclic hydrogen-bonded structures as a proton shuttle (active mechanisms).