Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 287

In the presence of O 2 , the C (5 ) radical is converted into the corresponding per-

oxyl radical [reaction (298)]. Upon its bimolecular decay with other peroxyl
radicals present, the oxyl radical is formed [reaction (296)]. An analogous oxyl
radical has been produced by thermally decomposing the tert -butyl ester of thy-
midine-5

′

′ -carboxylic acid (Montevecchi et al. 2004). These oxyl radicals under-

go ready -fragmentation [reaction (301)], and the most pronounced products of

this reaction are 2-hydroxytetrodialdose and Thy [reaction (302); Dizdaroglu et
al. 1976]. Interestingly, the HO 2 • -elimination [reaction (299)] is not sufficiently
fast to compete effectively at pH 7. For yields, see Table 10.27.

β

10.8.7
Base Release

The release of unaltered bases is a general phenomenon of the free-radical-in-
duced reactions of DNA and its constituents. The process is multi-phasic. Typi-
cally, a fraction is set free on the time-scale of the free-radical reactions or very
shortly afterwards (Table 10.30). Mechanistically, this could mean that a base
can already be eliminated at the free-radical stage (for an example see above) or
that a resulting non-radical product is very unstable. The determination of the
released bases (e.g., by HPLC) requires a couple of minutes. Thus, a fast hydro-
lyzing intermediate cannot be distinguished experimentally from processes oc-
curring at the free-radical stage. However, the slow component is certainly due
to unstable non-radical products. In the course of base release, the altered sugars
that gave rise to this instability of the N -glycosidic linkage are set free. Their
determination yields valuable information as to the structures of these labile
products and may even provide a clue as to the mechanism of their formation.