One-electron photooxidations of
5-methyl-2'-deoxycytidine (d(m)C) and 5-trideuteriomethyl-2'-deoxycytidine ([D(3)]d(m)C) by sensitization with
anthraquinone (AQ) derivatives were investigated. Photoirradiation of an aerated aqueous
solution containing d(m)C and
anthraquinone 2-sulfonate (AQS) afforded
5-formyl-2'-deoxycytidine (d(f)C) and
5-hydroxymethyl-2'-deoxycytidine (d(hm)C) in good yield through an initial one-electron oxidation process. The
deuterium isotope effect on the AQS-sensitized photooxidation of d(m)C suggests that the rate-determining step in the photosensitized oxidation of d(m)C involves internal transfer of the C5-hydrogen atom of a d(m)C-tetroxide intermediate to produce d(f)C and d(hm)C. In the case of a
5-methylcytosine ((m)C)-containing duplex
DNA with an AQ chromophore that is incorporated into the backbone of the
DNA strand so as to be immobilized at a specific position, (m)C underwent efficient direct one-electron oxidation by the photoexcited AQ, which resulted in an exclusive
DNA strand cleavage at the target (m)C site upon hot
piperidine treatment. In accordance with the suppression of the strand cleavage at 5-trideuterio-methylcytosine observed in a similar AQ
photosensitization, it is suggested that deprotonation at the C5-methyl group of an intermediate (m)C radical
cation may occur as a key elementary reaction in the photooxidative strand cleavage at the (m)C site. Incorporation of an AQ sensitizer into the interior of a strand of the duplex enhanced the one-electron photooxidation of (m)C, presumably because of an increased intersystem crossing efficiency that may lead to efficient
piperidine-induced strand cleavage at an (m)C site in
a DNA duplex.