Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 205

10.2
Radical Cations and their Conjugate Bases,
the Heteroatom-Centered Radicals

10.2.1
Formation of Radical Cations

In the direct effect of ionizing radiation on DNA, radical cations are the primary
products (Chap. 12). For this reason, their reactions are of considerable interest.
Obviously, photoionization (e.g., at 193 nm) and laser multi-photon excitation
leads to such species (e.g., Candeias and Steenken 1992b; Malone et al. 1995;
Chap. 2.2). Base radical cation electron pairs have been proposed to be the first
observable intermediates with a lifetime of 10 ps for Ade and four times longer
for the other nucleobases (Reuther et al. 2000). Radical cations are also assumed
to be intermediates in the reactions of photosensitization reactions with qui-
nones, benzophenone, phthalocyanine and ribof lavin (Cadet et al. 1983a; Decar-
roz et al. 1987; Krishna et al. 1987; Ravanat et al. 1991, 1992; Buchko et al. 1993;
Douki and Cadet 1999; Ma et al. 2000). Nucleobase radical cations may be pro-
duced by electrochemical oxidation (Nishimoto et al. 1992; Hatta et al. 2001) or
with strongly oxidizing radicals (for a compilation of their reduction potentials
see Chap. 5.3). Rate constants are compiled in Table 10.3.
One-electron oxidation of dGuo to its radical cation, G • + , is achieved by strong
ox id a nt s such a s Tl2+, Tl2+, 2+ , SO 4 • − and Br 2 • − (Table 10.3; for its EPR spectrum generated
by SO 4 • − see Bachler and Hildenbrand 1992) as well as the heteroatom-centered
radicals derived from the other nucleobases ( e.g., Shi et al. 2000a). Weaker oxi-
dants such as N 3 • and the dimeric tetramethylthiourea radical cation are capable
of oxidizing dGuo only at high pH, i.e. in its anionic form thereby producing the
guanyl radical, G • (Schuchmann et al. 2000). Depending on the nature of the oxi-
dant, oxidation may take place by direct ET as well as by addition-elimination.
Kinetic deuterium isotope effects of 1.5 2 are observed in the (reversible) oxida-

tion of Gua by 2-aminopurine radicals, and it has been concluded that this redox
equilibrium can be considered in terms of a proton-coupled ET (Shafirovich et
al. 2000). Such a proton-coupled ET step leads to a lowering of the overall free
energy of reaction thus favoring ET (Rehm and Weller 1970; Atherton and Har-
riman 1993; for theoretical calculations see Cho and Shin 2000 and references
cited therein).
Short-lived adducts may be formed as intermediates in the reactions of the
oxidizing inorganic radicals with the nucleobases, and it is therefore not always
fully excluded that processes observed at very short times and attributed to the
reactions of radical cations are in fact due to such intermediates. It may be men-
tioned that, for example, a long-lived SO 4 • − -adduct is observed in the reaction of
SO 4 • − with maleic acid (Norman et al. 1970). It has been suggested that SO 4 • − in
its reactions with the pyrimidines forms only an adduct and does not give rise
to radical cations (Lomoth et al. 1999). The observation of heteroatom-centered
radicals by EPR from the nucleobases Ura, Thy and Cyt (Catterall et al. 1992) as
well as dCyd (Hildenbrand et al. 1989) (see below) has been taken as evidence
that in the reaction of SO 4 • − with pyrimidines radical cations are likely, albeit

−