Theoretical study on the mechanism of alkylation at N-7 of guanine by few nitrogen mustards

Abstract

The interaction of aziridinium ion with N-7 of guanine is considered the common reaction step in the alkylation of DNA by nitrogen mustards. However, the involvement of another inter­mediate, carbonium ion is expected in some nitrogen mustards. The study on the energies of forming these inter­mediates indicates that carbonium ion is generated at different energy levels in the transition state and energetically less favourable, which might indirectly explain the experimentally observed lower alkylating abilities of some nitrogen mustards. These drugs acquire ability of generating aziridinium ion but substitution at N-4 might not enhance the reactivity of nitrogen mustards. Some drugs may generate another energetically less favourable carbonium ion intermediate.