A quantum chemical study of reactions of DNA bases with sulphur mustard: a chemical warfare agent

Reactions of the sulphonium ion of sulphur mustard (SM+1) at the N7, N3 and O6 sites of guanine, N7, N3 and N1 sites of adenine, O2 and N3 sites of cytosine and O2 and O4 sites of thymine were studied theoretically in gas phase and aqueous media employing density functional theory (DFT) and second order Moller-Plesset perturbation (MP2) theory. The B3LYP, B3PW91 and B1B95 functionals of DFT and the 6-31+G* and AUG-cc-pVDZ basis sets were used in the calculations. Basis set superposition error was treated using the counterpoise method by single point energy calculations at the B3LYP/6-31+G* level in gas phase. The present study explains the mechanism of alkylation of the DNA bases and shows that SM+1 would form stable adducts at the endocyclic nitrogen sites of the DNA bases, and at the O6 site of guanine and the O2 site of cytosine. Formation of adducts at the N7 site of guanine and N3 site of adenine are found to be most favored and next most favored respectively, which agrees with experimental observations.