Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 223

Table 10.7. Reactions of • OH with some pyrimidines. Yields of addition at C (5) and C (6).
H-abstraction where applicable. (Fujita and Steenken 1981; Al-Sheikhly and von Sonntag
1983; Hazra and Steenken 1983)

Pyrimidine Addition at C(5) Addition at (C6) H-Abstraction

Ura 82 18 -

Thy 60 30 10

6MeUra 88 12 Little

Isoorotic acid 63 37 -

Orotic acid 86 14 -

1,3Me 2 Ura 78 17 Little

poly(U) 70 23 7

Cy t 87 10 -

1MeCy t 87 8 -

2MeCyt 92 10 -

5MeCyt 65 22 13

5CarboxyCyt 82 24 -

mechanisms involving consecutive additions of two • OH that still continue to be
considered in the literature [e.g., Jaussaud et al. 2000] have to be rejected.
The basic form of • OH, O • − [p K a ( • OH) = 11.8], reacts much more slowly with
the nucleobases (Ioele et al. 1998) that are all deprotonated at the pH where O • −
predominates (Table 10.11). It will be shown below that • OH and O • − differ sub-
stantially in their reactions.

10.3.2
Determination of the Site of • OH-Attack

Pyrimidines. When • OH reacts with the pyrimidines, it adds to the C (5)− C (6)
double bond, and in the case of Thy it also abstracts to a minor extent an H-atom
from the methyl group [reactions (59)−(61)]. A radical at C (6) is formed upon
addition at C (5) [reaction (59); for EPR studies see, e.g., Hildenbrand et al. 1989;
Schulte-Frohlinde and Hildenbrand 1989; Catterall et al. 1992; for DFT calcula-
tions, see Wetmore et al. 1998b]. This radical has reducing properties due to the
interaction with the electron pair at the neighboring nitrogen, and in a pulse ra-
diolysis experiment its yield can be determined by its rapid reaction with TNM
which yields the strongly absorbing nitroform anion [reaction (62); ε (350nm) =

15,000 dm 3 mol −1 cm −1 ].