Carbon-Centered Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 110

from the substrate (von Sonntag and Thoms 1970). Possibly, this type of radical
has to be made responsible for the formation of DNA SSBs induced by glycerol-
derived radicals at high scavenger concentrations (Chap. 12.1).
The mechanism of this water elimination and related reactions, where the
OH group in -position is replaced by another leaving group (L), has been stud-

ied in some detail (Samuni and Neta 1973; Steenken et al. 1974; Behrens and
Schulte-Frohlinde 1976; Behrens and Koltzenburg 1985; Schuchmann et al. 1995;
Müller et al. 1997; Bales et al. 2001). Two processes which compete with one an-
other have been recognized: heterolytic cleavage of the C

β

L bond which results
in the formation of a radical cation followed by proton loss [reactions (36) and
(37)] and the dissociation of the hydroxyl group followed by the loss of the leav-
ing group [reactions (38 and (39)].

−

The rate of the elimination of the ligand [reactions (39) and (39)] is determined
by the electrophilicity of the frame and the nucleofugacity of the ligand (Beh-
rens and Koltzenburg 1985). Deprotonation of the frame [reaction (38)] strongly
reduces its electrophilicity, and thus the radical anion may eliminate quite well
also ligands which have an intrinsic poor nucleofugacity such as OH [see below;
cf. reaction (39)]. The rate of reaction (38) is determined by the p K a value of the
α

-hydroxyalkyl radical and is thus strongly inf luenced by the substituents R and
L. As a measure of the nucleofugacity the p K a value of the conjugate acid of the
leaving group may be taken: HCl (negative p K a ), CH 3 CO 2 H (4.7), NH 4 + (9.3), i.e.
a high p K a corresponds to a low nucleofugacity. Thus, the OH group (p K a (H 2 O)
= 14) is also a poor leaving group. However, upon protonation it becomes a very
good leaving group (p K a (H 3 O + ) is negative), and this is the reason why the water
elimination is also acid catalyzed [cf. reaction (31); Steenken 1979; Steenken et
al. 1986a].
A much simpler situation is the anion loss from an

α -alkoxyalkyl radical

with a leaving group in the -position, such as the phosphate release from the 2-

phosphato-methoxyethyl radical (Behrens et al. 1978; for some further reactions
of

β

-(phosphatoxy)alkyl radicals see Whitted et al. 1999; Crich et al. 2000). This
reaction only proceeds by a heterolytic cleavage into a radical cation and a phos-
phate ion. The rate of this reaction strongly depends on the protonation state of
the phosphate group [reactions (40)−(44)].

β