Theoretical structure-activity study of mutagenic allyl chlorides

Abstract

Ab initio molecular orbital calculations at the STO-3G and 3-21G levels were used to clarify the mechanism of mutagenic action of various substituted allyl chlorides. Computed molecular properties were compared with experimental mutagenic potentials of these allylic compounds. In agreement with experiment, the computational results suggest that the primary mechanism of action involves the SN1 formation of allylic cations which then react with nucleophilic centers of nucleic acid bases. The usefulness of computed properties in estimating the degree of alkylating activity and mutagenicity was evaluated. In general, stability of the allylic carbocation intermediate and the degree of charge delocalization in the allyl system correlate well with observed mutagenic potentials.