The Hydroxyl Radical - Free-Radical-Induced DNA Damage and Its Repair - page 45

3.1
General Properties

The various ways of forming • OH were discussed in Chapter 2. It is a very reac-
tive, electrophilic ( 0.41; Anbar et al. 1966a) radical, and with most sub-

strates it reacts at close to diffusion-controlled rates (for a compilation of rate
constants, see Buxton et al. 1988). It undergoes mainly three types of reactions:
(1) addition to C

ρ = −

N double bonds, (2) H-abstraction and (3) ET. Addi-
tion and H-abstraction reactions will be discussed below in some detail, because
they are relevant for an • OH-attack at the nucleobases and at the sugar moiety
in DNA.
Although it is of little importance at the pH values that prevail in biological
systems, it must be mentioned that at high pH • OH deprotonates [equilibrium
(1), p K a ( • OH) = 11.8 (Weeks and Rabani 1966), 11.54 (Poskrebyshev et al. 2002);
for its temperature dependence see Elliot and McCracken (1989); for UV spectra
see Czapski and Bielski (1993) and Poskrebyshev et al. (2002)].

− C and C −

(1)

The O • − radical may also be generated in neutral solution (e.g., e aq − + N 2 O O • − →

+ N 2 ; NO 3 − + h 10 8

s −1 ) that its reaction with a given substrate can be neglected (cf. Mark et al. 1996),
and only the typical • OH reactions are observed. Thus O • − reactions only occur
to a significant extent at pH > 12.
The (nucleophilic) O • − radical still undergoes H-abstraction at a high rate
(for the energetics, see Henglein 1980), but its ability to add to double bonds is
strongly reduced (for a compilation of rate constants, see Buxton et al. 1988). For
example, in nucleosides the preference of attack at the base is shifted at high pH
towards a pronounced H-abstraction from the sugar moiety (Scholes et al. 1992).
An important difference between the (electrophilic) • OH and its conjugate base,
the (nucleophilic) O • − , is their reactivity towards O 2 . While O 2 does not react
with • OH, it readily adds to the electron-rich O • − , yielding the ozonide radical
anion [equilibrium (3); p K = 6.26; for details, see Elliot and McCracken 1989].

• NO 2 + O • − ), but it is so rapidly protonated by water ( k −1

ν → ≈

• OH + O 2

→ no reaction (2)

(3)

3.2
Addition to Double Bonds

The electrophilic • OH reacts readily with C C and C N double bonds (in purines)

− −

but not with C O double bonds which are electron-deficient at carbon, the posi-

tion where • OH would prefer to add. Although • OH reacts with C

−

C double bonds
at close to diffusion-controlled rates, it is highly regioselective largely due to its

−