Heteroatom-Centered Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 127

7.1
General Remarks
With the nucleobases, radicals may be formed which carry the spin predomi-
nantly at a heteroatom, oxygen or nitrogen. In addition, the importance of gluta-
thione and possibly also the surrounding proteins in modifying DNA free-radi-
cal damage in a cellular environment will at one stage involve heteroatom-cen-
tered radicals, that is, also at sulfur. In many aspects, heteroatom free-radical
chemistry differs from that of carbon-centered radicals, although these radicals
are often highly delocalized with a considerable spin density at carbon.
When the binding energy of a hydrogen to a heteroatom is weak, heteroatom-
centered radicals are readily produced by H-abstraction or one-electron oxida-
tion followed by H + loss. Typical examples are phenols (e.g., vitamin E in non-
aqueous media), tryptophan and related compounds and thiols. Deprotonation
of radical cations is indeed often a source of heteroatom-centered radicals even
if a deprotonation at carbon or OH − addition upon reaction with water would be
thermodynamically favored. The reason for this is the ready deprotonation at a
heteroatom (Chap. 6.2).
Among the oxygen-centered radicals, • OH and ROO • play a major role, and
their chemistries are discussed in Chapters 3 and 8, respectively. Here we deal
with some other oxygen-centered species such as RO • and phenoxyl radicals.
Oxyl radicals are formed in the bimolecular decay of peroxyl radicals (Chap. 8.8),
thermal and photolytic decomposition of peroxides or their reductive cleavage
(Chaps 2.4 and 3.3). Due to their short lifetime, which is discussed below in some
detail, their DNA damaging property is only marginal (Chap. 2.4). The aromatic
phenoxyl radicals, on the other hand, are of little reactivity, but they seem to
take part in DNA-protein cross-linking. They have also some oxidizing prop-
erties and may be taken as model systems for the guanine radical, G • , whose
chemistry is as yet not fully elucidated.
The chemistries of nitrogen-centered and sulfur-centered radicals have been
reviewed in detail (Alfassi 1997, 1999), and here only some aspects can be dis-
cussed that seem pertinent to the formation, reactions and repair of DNA radi-
cals.
A common feature of heteroatom-centered radicals is that they react revers-
ibly, only slowly or not at all with O 2 (Schuchmann and von Sonntag 1997), and
this property is shared by the purine radicals G • and A • (Chap. 10.2).
7. 2
Oxygen-Centered Radicals
The logarithm of the rate constants of H-abstraction by reactive oxygen species
decreases with decreasing O-H bond dissociation energy from • OH [BDE(HO-
H) = 497 kJ mol − 1 ] > RO • [BDE(RO-H) = 439 kJ mol − 1 ] > ROO • [BDE(ROO-H) =
372 kJ mol − 1 ], and this sequence also includes the even less reactive metal-oxo
complexes, e.g., permanganate (Mayer 1998).