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The process of cleavage of PyrO Pyr ends with formation of a monomeric Pyr and its radical cation Pyr'+. The latter was found to initiate a radical chain by oxidation of further PyrO Pyr [8, 13]. In DNA, however, an analog chain reaction which would amplify the oxidative repair of pyrimidine dimer-derived damages could only be possible by long-range electron/hole transfer, because the oxidized nucleobase Pyr'+ is located at a fixed position in an oligonucleotide strand [14].

Besides electron transfer, alternative pathways have also been proposed in literature for the initial step in the cleavage of Pyr<> Pyr. Heelis et al. [15a] and Gross-weiner et al. [15b] observed that hydroxyl radicals (HO') and sulfate radical anions (SO4'_), both generated by pulse radiolysis in aqueous solution, were able to cleave c,s-3 to the monomer. Despite the high oxidizing strength of HO' (E0 HO'/ OH~ = 2.7 V relative to the NHE) [16], which lead Grossweiner et al. to the assumption of electron transfer as initial reaction step [15b] the reactions of with organic substrates in aqueous solutions rarely proceed by direct electron transfer but generally occur either by addition to p systems or by hydrogen abstraction. Although the detailed mechanism for thymine production from c,s-3 by HO' is not yet known, hydrogen atom transfer, presumably from C(6) or C(6'), was assumed to be the primary step.

The magnitude of the rate constant of the SO4'^-induced splitting of c,s-3, determined by Heelis et al. [14] from computer simulation of the build-up of thy-mine, also indicated hydrogen abstraction as the initial reaction step, even though SO4'~ is a very strong one-electron oxidant (E0 SO4'~/SO42~ = 2.4 V relative to the NHE) [16] and hydrogen abstractions by SO4'~ are usually several orders of magnitude slower than electron transfer [17]. Actually, the SO4'~- or N3'- (E0 N3'/ N3~ = 2.7 V relative to the NHE) [16, 18] initiated splitting of the stereoisomeric C(5)-C(5') linked dihydrothymine dimers 14 into the thymines 15 and 5,6-dihydrothymines 16 in aqueous solution has been suggested to proceed through initial electron transfer (Scheme 4.5.7) [19].

Scheme 4.5.7.
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