Ionizing radiation damages DNA by direct ionization of the nucleobases or indirectly, through the production of hydroxyl radical, that then reacts with DNA. The intermediacy of pyrimidine radical cations (e.g. 1) has been proposed based upon the products formed upon irradiation of thymidine and polyuridylic acid. Nucleobase radical cations are proposed to be important intermediates in the formation of modified nucleotides and strand breaks. These intermediates have never been independently generated from synthetic precursors. We present compelling evidence for the first independent generation of the thymidine radical cation (1,   generated from the 350 nm photolysis of 2) at a defined site within DNA. The major product arising from 1  is an interstrand cross-link (ICL), formed between 3  and the opposing dA (4). We propose a mechanism for the formation of these ICLs involving 1. The details of this chemistry in monomer studies and within DNA will be discussed.

Interstrand DNA cross-link formation from a pyrimidine cation radical

244th National Meeting (2012)

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