Anthraquinone-Sensitized Photooxidation of 5-Methylcytosine in DNA Leading to Piperidine-Induced Efficient Strand Cleavage
✍ Scribed by Dr. Hisatsugu Yamada; Yuya Kitauchi; Dr. Kazuhito Tanabe; Dr. Takeo Ito; Prof. Dr. Sei-ichi Nishimoto
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 476 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0947-6539
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✦ Synopsis
Abstract
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.