Free-Radical-Induced Transformations of Damaged Nucleobases

Free-Radical-Induced Transformations of Damaged Nucleobases 

A number of studies are concerned with the free-radical reactions of typical nucleobase lesions. For example, the cyclobutane-type Thy dimer can be split by one-electron reduction [Heelis et al. 1992 reactions (307) and (308)], a process that is relevant to the repair of this typical UV-damage by the photoreactivating enzyme (photolyase, for a review see Carrell et al. 2001, for the energetics of the complex reaction sequence, see Popovic et al. 2002). At 77 K, the dimer radical anion is sufficiently long-lived to be detectable by EPR (Pezeshk et al. 1996). 

The dimer can be split by eaq and by other reducing radicals such as C02 or C(CH3)2OH, albeit with a much lower efficiency. The resulting Thy radical anion is also capable of transferring an electron to the Thy dimer, and this leads to a short chain reaction. 

The C(5)-C(5 )-linked dihydrothymine dimers are also readily split by eaq [reaction (309)] forming H2Thy but also Thy in appreciable yields (Ito et al. 2000). 

Reaction with OH also leads to the splitting of the dimer (-30% efficiency), and there is evidence that one-electron oxidants such as S04 may also induce the splitting of the dimer (Heelis et al. 1992). The NO -radical-induced splitting of the tetramethyl-substituted Ura cyclobutane dimer has been investigated in acetonitrile (Kruger and Wille 2001). The -N03 radical has been generated photo-lytically from a Ce(VI) salt (Chap. 5.2). Under theses conditions, the 5-5 -linked intermediate is also trapped, possibly by a deprotonation or a Ce(IV)-mediated oxidation that competes with 3-fragmentation [reactions (310)—(313)]. 

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Free-Radical-Induced Transformations of Damaged Nucleobases 308... 

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