Heteroatom-Centered Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 137

When the amino group is fully deprotonated, the rate of the H-transfer is ∼ 1.5

10 5 s − 1 , but also around pH 7 the reaction is still fast, at the ms timescale (for a
quantum mechanical study see Rauk et al. 2001). Upon the decay of the amnioal-
kyl radicals formed in reaction (35) ammonia as formed in a yield that points to
disproportionation as the major process (Zhao et al. 1997). The fact that the ami-
noalkyl radical is the thermodynamically favored species does not mean that the
repair of DNA radicals by GSH (Chap. 12.11) is not due to its action as a thiol.
As with many other examples described in this topic, the much faster kinetics
that lead to a metastable intermediate (here: the formation of the thiyl radical)
rather than the thermodynamics as determined by the most stable species (here:
the aminoalkyl radical) determine the pathway the the reaction. In fact, the C

×

− H

BDE of the peptide linkage is lower than the S H BDE and repair of DNA radicals

by peptides, e.g., proteins would be thermodynamically favored over a repair by
thiols but this reaction is retarded kinetically (Reid et al. 2003a,b).
Considering the ability of thiyl radicals to abstract

−

H, the ques-
tion comes to mind, whether they might induce SSBs in DNA by abstracting the
C (4

α -alkoxy-C −

H-abstraction. To
our knowledge, this has never been shown, but conditions may be thought of,
where this reaction can proceed in vitro. In vivo, GSH is the dominating thiol. Its
thiyl radical has only a rather short intrinsic lifetime [reaction (35)], and this will
strongly reduce the probability of attacking the sugar moiety. Moreover, GSH is
negatively charged and so is GS • . This additionally reduces the rate of reaction
notably within the minor groove with its high negative charge density.
In contrast to their oxygen- and nitrogen-centered analogs [reactions (6) and
(25)], 1,2-H-shift reactions of thiyl radicals are not only slow but the equilibrium
lies practically fully on the side of the thiyl radical [reaction (36); Zhang et al.
1994; Naumov and von Sonntag 2005].

′ ) − H or induce β→α -anomerizations at C (1 ′ ) after C (1 ′ ) −

This equilibrium is only of any consequence when one of these two radicals does
not react (or reacts reversibly) with a given substrate, while the other does (O 2 is
an example; Chap. 8.2).