Peroxyl Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 160

The ROO H BDE in hydroperoxides derived from weakly oxidizing peroxyl radi-

cals is ca. 360-370 kJ mol − 1 (Khursan and Martem'yanov 1991; Denisov and Den-
isova 1993), and, for a peroxyl radical reaction to occur at an appreciable rate,
the C

−

H BDE of the donor must be sufficiently low. A case in point is aliphatic
amines, but even with these the rate constants are rather low ( k < 500 dm 3 mol − 1
s − 1 at 350 K; Dambrova et al. 2000). In DNA, the weakest C

−

H bond is that of the
allylic hydrogen in Thy, and this is the preferred site of peroxyl radical attack
(Razskazovskii and Sevilla 1996; Martini and Termini 1997). In poly(U), nucleo-
base peroxyl radicals abstract the C (2

−

′ ) − H that is activated by the neighboring

OH group (Chaps 9.4 and 11.2), but C (2 ′ ) − H abstraction in DNA is inefficient due

to the higher BDE of this hydrogen.
Because of the often slow rate of reaction, even of intramolecular H-abstrac-
tion and a favorable six-membered transition state such as in reaction (29) ( k

≈

1 s − 1 ; Schuchmann and von Sonntag 1982; for further examples see, e.g., Ulanski
et al. 1996a,b), the reaction is only observed at a low steady-state of peroxyl radi-
cals, that is, when the lifetime of peroxyl radical is long. Kinetic parameters with
pre-exponential factors near 10 8 and activation energies varying from 30-60 kJ
mol − 1 have been reported for the reactions of peroxyl radicals with various alco-
hols (Denisov and Denisova 1993).
As a consequence of the reformation of the starting radical, a chain sets in
[reactions (31)-(33)].

R • + O 2 → RO 2 • (31)

RO 2 • + RH → RO 2 H + R • (32)

2 RO 2 • → Products (33)

If this mechanism is strictly followed the chain length and hence the value of
O 2 -uptake (see below) increases linearly with the substrate concentration and
(initiation rate) − 1/2 (i.e., in radiolytic studies the dose rate) and in charged poly-
mers also on the pH (cf. Ulanski et al. 1996a). In polymers, the chain reaction
may mainly proceed intramolecularly (Ulanski et al. 1996a; Janik et al. 2000).
An example for an efficient intramolecular autoxidation is poly(acrylic acid) [re-
actions (34)−(36); Ulanski et al. 1996a]. In these autoxidation reactions, hydro-
peroxides are formed which, in some cases, are quite unstable [e.g. reaction (37);
see also Leitzke et al. 2001].
In micellar systems, the chain peroxidation reaction only becomes effective
at the critical micelle concentration where the substrate molecules aggregate
thereby forming locally high concentrations (Gebicki and Allen 1969).
The hydroperoxides that are formed in all these autoxidation reactions all
have low O H BDEs. As a consequence, hydroperoxides are good H-donors in

non-aqueous media, and they are often used to intercept radicals by H-dona-
tion. However, in water, where this function is hydrogen-bonded, the H-abstrac-
tion rates can drop by several orders of magnitude; the same phenomenon is
observed with phenols (Das et al. 1981; Avila et al. 1995; Valgimigli et al. 1995;
Banks et al. 1996; see also Ulanski et al. 1999).

−