Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 239

While 8-oxo-A is formed in the peroxynitite reaction with dAdo (Douki and Ca-
det 1996), 8-oxo-G (from dGuo) is not detected (Douki and Cadet 1996; Uppu et
al. 1996) due to its much faster reaction with this reagent (Uppu et al. 1996).
Unless a non-radical mechanism accounts for the formation of 4,5-dihydro-
5-hydroxy-4-(nitrosooxy)-2 -deoxy-

guanosine • OH-adduct via its O -centered mesomeric form in contrast to the ni-
tration of tyrosine, where • NO 2 reacts as an N -centered radical (van der Vliet et
al. 1994; Lymar et al. 1999).

′ -deoxyguanosine, • NO 2 must add to the 2 ′

10.3.5
Products in the Presence of Oxygen

In the presence of O 2 , most radicals are converted into the corresponding per-
oxyl radicals with the notable exception of heteroatom-centered radicals which
do not react with O 2 at an appreciable rate (Chap. 8.2). However, even though
peroxyl radical reactions may dominate in the reactions induced by the autoxi-
dation of Fe(II)EDTA or Fe(II)NTA (Chap. 2.5), in the case of 2 -deoxynucleo-

sides the subsequent reactions seem to be considerably modified by the presence
of the transition metal ion, i.e. product ratios are found in these reactions which
are different from those observed by ionizing radiation in the absence of Fe(II)/
Fe(III) (Murata-Kamiya et al. 1998). A basis for understanding these differences
may be the various redox reactions that the peroxyl radicals will undergo with
Fe(II)/Fe(III) (cf. Yurkova et al. 1999; Theruvathu et al. 2001; see also Chaps 2.5
and 8.3).

′

Pyrimidines. The pyrimidine- • OH-adducts react with O 2 at close to diffusion-
controlled rates yielding the corresponding peroxyl radicals ( k 10 9 dm 3

mol −1 s −1 ; Willson 1970). In basic solutions, but also in neutral solutions as long
as the (dominating) C (6)-peroxyl radical has a sufficiently long lifetime, it un-
dergoes O 2 • − -elimination after deprotonation at N (1) [reactions (121) and (122)]
(Schuchmann and von Sonntag 1983). Details of this kind of O 2 • − -elimination,
including the determination of the p K a value of the peroxyl radical, has been
studied for a very similar system, glycine anhydride (Mieden et al. 1993). In re-
action (122) an isopyrimidine (5-hydroxyisouracil) is formed. This product is
only short-lived and undergoes a rearrangement into isobarbituric acid [reac-
tion (124)] and hydration yielding Ug [reaction (123)]. Such reactions which will
be discussed in more detail below.

≈ 2 ×