Direct Time-Resolved Spectroscopic Observation of Arylnitrenium Ion Reactions with Guanine-Containing DNA Oligomers

Abstract

The metabolic activation of a number of aromatic amine compounds to arylnitrenium ions that can react with DNA to form covalent adducts has been linked to carcinogenesis. Guanine in DNA has been shown to be the main target of N-containing carcinogens, and many monomeric guanine derivatives have been utilized as models for product analysis and spectroscopic investigations to attempt to better understand the reaction mechanisms of DNA with arylnitrenium ions. However, there are still important unresolved issues regarding how arylnitrenium ions attack guanine residues in DNA oligomers. In this article, we employed ns-TA and ns-TR3 spectroscopies to directly observe the reaction of the 2-fluorenylnitrenium ion with selected DNA oligomers, and we detected an intermediate possessing a similar C8 structure as the intermediates produced from the reaction of monomeric guanosine derivatives with arylnitrenium ions. Our results suggest that the oligomeric structure can lead to a faster reaction rate of arylnitrenium ions with guanine residues in DNA oligomers and the reaction of arylnitrenium ions take place in a manner similar to reactions with monomeric guanosine derivatives.