Modification of DNA by alkylating agents has long been suspected as a mechanism of genotoxicity. A definite relationship linking SN1 activity and genotoxicity has been established experimentally. Alkyl methanesulfonates serve as good examples of DNA alkylating agents with mutagenicity verified by the Ames test. Genotoxicity has been determined as the SOS inducing potential (SOSiP) for a series of alkyl methanesulfonates as a function of the sfi A gene linked �-galactosidase activity as a measure of the induction of SOS repair utilizing the PQ37 strain of E. coli. SOSiP values have been correlated with molecular properties computed for gas phase and solution phase (SM8 Model) with density functional theory at the B3LYP/6-31G(d,p) level. Carbocation intermediates from the methanesulfonates serve as good models of the genotoxic potential. Good correlations with SOSiP were obtained for the free energy of carbocation formation from the sulfonate esters, hydrophobicity, and percent polar surface area.

DFT modeling of DNA alkylation and genotoxicity of methanesulfonate esters

247th National Meeting (2014)

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