Neutral purine radicals are important reactive intermediates of oxidative damage of DNA and DNA charge transfer. However, the understanding of their reactivity is limited due to the lack of means to generate them in a controlled manner. Herein we descried an approach for the site specific, independent generation of the 2'-deoxyadenosine-N6-yl radical (dA●). The method involves sequential Norrish Type I photocleavage and β-fragmentation of the initially formed alkyl radical to form dA● in high fidelity and efficiency. The reactivity of dA● in DNA was investigated. dA● cannot initiate efficient hole migration in DNA, even the process is thermodynamically favorable. dA● degrades to deoxyinosine which is potentially mutagenic. A tandem lesion is formed in oligomers in the presence of oxygen. Experiments suggest the formation of this tandem lesion is initiated by the addition of dA● to 5’ adjacent thymidine following the formation of a thymidine peroxy radical analogue, which damages adjacent deoxyguanosine to give 8-oxo-deoxyguanosine.

Independent generation of 2'-deoxyadenosine-N6-yl radical and its reactivity in DNA

254th National Meeting (2017)

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