Carbon-Centered Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 108

6.8.2
Addition to C−N Double Bonds

Technically, the addition of carbon-centered radicals to C N double bonds is

as yet of little if any importance. In the free-radical chemistry of DNA it plays,
however, a considerable role in the formation of the C (5

−

C (8) linkage between
the sugar moiety and the purines (Chap. 10.5). Because of its importance, even
an immune assay has been developed for the sensitive detection of this kind of
damage in DNA (Chap. 13.2). The addition of the C (5

′ ) −

) radical to the C (8) posi-
tion of a purine is obviously facilitated for steric reasons (formation of a six-
membered ring), but the same kind of reaction also occurs as an intermolecular
reaction. Since alkyl radicals are nucleophilic, the rate of this reaction is notice-
ably increased upon protonation of the purine (Aravindakumar et al. 1994; for
rate constants see Chap. 10.5).
This addition reaction is not restricted to

′

-hydroxyalkyl radicals, although
this type of radical has been most widely investigated. Thus, allylic radical de-
rived from 5MeCyt (Zhang and Wang 2003) and radicals derived from amino
acids (Elad and Rosenthal 1969) are also reported to undergo this reaction. In
DNA, they play a role in the formation of tandem lesions (Chap. 12.5), and it is
likely that this kind of reaction contributes to free-radical-induced DNA/DNA
and DNA/protein cross-linking.

α

6.9
β

-Fragmentation Reactions

6.9.1
Homolytic Fragmentation

Carbon-centered radicals may undergo homolytic -fragmentation reactions,

whereby an olefin and a new radical is formed. This reaction is, in fact, the re-
verse of the polymerization reaction. With neighboring C

β

-frag-
mentation reactions are usually slow, and only observable, at least on the pulse
radiolysis time-scale with negatively-charged polymeric radicals whose lifetime
is prolonged by electrostatic repulsion. Then, even the situation of equilibrium
polymerization may be approached (Ulanski et al. 2000; Chap. 9.4).
In the nucleobases, this type of reaction is not possible due to the lack of ad-
equate structural elements.
There is a wealth of information available on the free-radical reactions of
carbohydrates in aqueous solution and in the solid state (for reviews see von
Sonntag 1980; von Sonntag and Schuchmann 2001). According to this, there is
no indication that

− C bonds, these β

β -fragmentation involving C − C double bond formation is a

major process in such systems. However, O double

bond is quite common, e.g., in disaccharides, where such a process can lead to
the scission of the glycosidic linkage. It is a lso obser ved in monosaccharides, no-
tably in 2-deoxyribose in the crystalline state (Hüttermann and Müller 1969a,b;
von Sonntag et al. 1974; Schuchmann et al. 1981), where it is present as the

β -fragmentation forming a C −

-py-

β