The Hydroxyl Radical - Free-Radical-Induced DNA Damage and Its Repair - page 48

tron donation [such as NR 2 ] favor abstraction of a given hydrogen atom.

On the other hand, neighboring electron-withdrawing groups such as carbonyl
functions decrease the rate of H-abstraction by the electrophilic • OH. Thus, its
rate with acetic acid is rather low ( k

− OR or −

10 7 dm 3 mol −1 s −1 ), while that with the
somewhat electron-richer acetate ion is noticeably faster ( k

≈

10 8 dm 3 mol −1 s −1 ;
Buxton et al. 1988). Here, it is worth mentioning that in the case of electrophilic/
nucleophilic radicals the site of H-abstraction may be reversed, that is, C

≈

H BDE
is only one factor that governs the site of attack (Brocks et al. 1998). It has been
suggested that a combination of electron donation and electron withdrawal (the
push-pull effect) additionally favors H-abstraction (Viehe et al. 1985). Whether
this effect or just the contribution of electrophilicity is the reason for the re-
markable free-radical chemistry of amino acid anhydrides, is not yet known.
In the series of amino acid anhydrides, H-abstraction by • OH occurs at the pep-
tide carbon [cf. reaction (16)], and in alanine anhydride an H-abstraction at the
methyl group is not observed. In sarcosine anhydride, however, H-abstraction
at the methyl group (22%) is an important process (Mieden and von Sonntag
1989).

−

Glycine anhydride

Alanine anhydride Sarcosine anhydride

Dihydrouracil, an isomer of glycine anhydride, has two kinds of carbon-bound
hydrogen atoms. Those activated by the neighboring NH-group react much
more readily (90%) than those next to the carbonyl function (ca. 5%; Schuch-
mann et al. 1984; for details, see Chap. 10). Thus, a high regioselectivity is again
observed.
In the case of amines, protonation that withdraws electron density from
the center of reaction lowers the rate of reaction by a factor of 30 (Das and von
Sonntag 1986). Besides H-abstraction from carbon [reactions (18) and (21)], the
formation of N -centered radical cations is observed [reactions (19)/(22) and (20);
for amino acids see, e.g., Bonifacic et al. 1998; Höbel and von Sonntag 1998].
Reaction (20) is also an H-abstraction reaction. The ET reaction (19)/(22) may
proceed via a (bona-fide, very short-lived) adduct (Chap. 7).