DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 412

Compared to hole transfer, ET through DNA has found less attention (Wa-
genknecht 2003). DFT calculations indicate, that the electron affinities of the
nucleobases are U

I (hypoxanthine) > A > G with G being nearly
1 eV less electron affinic than U (Li et al. 2002). While in hole transfer, the most
preferable trapping site is a GGG triplet, ET moves towards pyrimidine triplets
whereby there is little energetic difference between XCY or XTY (X, Y = T or C)
sites (Voityuk et al. 2001). Using brominated nucleobases (e.g., 5-bromo-6-hy-
droxy-5,6-dihydrothymine) as intramolecular electron scavenger indicates that
excess electrons may travel through DNA about 11 bp at 77 K (Razskazovskii et
al. 1997). Intercalated mitoxantron has been used to follow the transfer of excess
electrons at 77 K through hydrated solid DNA (21 waters per nucleotide) and in
frozen DNA solutions (Cai et al. 2000; Cai and Sevilla 2000), and similar

≈ T > C ≈

β val-

1 bp min −1 ) and ET distances were found for both systems (for further
studies see Cai et al. 2001). From a series of similar experiments, a tunneling
constant

ues (10 ±

of 0.8-1.2 Å −1 has been derived at (Messer et al. 2000; Cai et al. 2002).
It is concluded that at 77 K DNA is not an especially effective conduit for the
transfer of excess electrons. The rate of ET through DNA to electron-affinic in-
tercalators in aqueous solution depends on the free-energy change and distance
(Anderson and Wright 1999). Migration of excess electrons does not proceed
through ssDNA (Shafirovich et al. 1997).
The light-induced repair of cylobutane-type dimers by the enzyme photoly-
ase is of major biological importance. This proceeds by ET from a f flavin, and
using a model system it has been shown that the electron is likely to be funneled
through the DNA base stack (Schwögler et al. 2000).

β

12 .11
Protection of DNA Against Free-Radical Attack

12 .11.1
General Remarks

The trivial case, where DNA and a given additive compete for a reactive free radi-
cal, will not be discussed here, as long as competition kinetics are involved (a case
in point would be the scavenging of DNA-damaging radicals by cell-permeable
stable radicals such as nitroxides; Offer and Samuni 2002; Sasaki et al. 1998; Da-
miani et al. 2000). Due to polymeric properties of DNA, the competition kinetics
are non-homogeneous (for a model that describes this situation adequately see
Mark et al. 1989; Udovicic et al. 1991a; for an earlier spherical model see van Rijn
et al. 1985), and competition with simple low-molecular-weight compounds fol-
lows indeed this model over a wide concentration range (Udovicic et al. 1991b,
1994). Any protection beyond this simple competitive radical scavenging can
be assessed by calculating the contribution of competitive radical scavenging
on the basis of the above model and the rate constants of a given radical with
DNA and the competitor ( k ( • OH + DNA) = 4.5 10 8 dm 3 mol −1 s −1 - Liphard et

×

10 8 dm 3 mol −1 s −1 - Michaels and Hunt 1973;
for compilation of • OH rate constants see Buxton et al. 1988). If the scavenger is

al. 1990; Udovicic et al. 1994; 4 ×