Polymer Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 185

9.1
General Remarks

Linear man-made polymers and also some biopolymers may have only one re-
peating unit, but often there are more than one repeating unit which do not fol-
low one another in a regular way. With its four nucleotides as repeating units,
DNA is a typical example. In solution, neutral linear polymers attain a coil-like
conformation. In charged polymers, the charges repel each other, and the con-
formation of the polymer becomes rod-like. The local density of the repeating
units and the conformation of the polymer chain have a dramatic effect on some
of the properties of the free-radical chemistry of the polymer (Ulanski et al.
1997). Quite a number of the properties of DNA radicals can be understood if it
is taken into account that DNA is a highly charged polymer.

9.2
Rate of Formation of Polymer Radicals

The rate of reaction of neutral free radicals such as • OH with a polymer or an
equal concentration (in g dm − 3 ) of its subunits is generally much lower for the
polymer than that of the low molecular weight compound. The low molecular
weight molecules are randomly distributed throughout the solution, while the
polymer chains do not fill equally well the whole space. Thus, the average dis-
tance that a reactive free-radical has to travel to reach the target molecule is
much longer in the case of the polymer. Experimentally, this has been shown
with many synthetic polymers (Behzadi et al. 1970; Ulanski et al. 1995), and the
rate of reaction of DNA with • OH is also much lower (2.5 10 8 dm 3 mol − 1 s − 1 ;

Udovicic et al. 1994; for corresponding data on polynucleotides see Michaels and
Hunt 1973) than that with nucleotides (

×

10 9 dm 3 mol − 1 s − 1 ; for a compilation
see Chap. 10.3). The rate constants of • OH are often determined in competition
with SCN − . With charged polymers such as DNA or poly(A) (Loman and Ebert
1968), this may lead to complications and eventually to erroneous results due to
a repulsion of SCN − from the highly charged polymer (Ulanski and von Sonntag
2000).
The rate of reaction of e aq − with charged polymers such as polynucleotides
is much lower than that of parent bases (Shragge et al. 1971). An electrostatic
repulsion of e aq − by the negatively charged polymer adds to the effect discussed
above. These much lower rates of polymers as compared to their subunits also
allows one to determine the binding constants of drugs, e.g., ethidium bromide
to DNA (Greenstock et al. 1977).
Competitive scavenging of reactive free radicals, such as • OH, by DNA and
other substrates, is a very important aspect of DNA free-radical chemistry. This
situation has been modeled by various approaches (van Rijn et al. 1985; Laf leur
and Loman 1986; Verberne et al. 1987). The most recent model has been devel-
oped by Udovicic et al. (1991).
Increasingly, Monte-Carlo calculations become available, which try not only
to describe the general rate of reactions but also the sites of attack within the

∼ 3 ×