Carbon-Centered Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 104

spin polarization in the transition state, as determined by AIM analysis and
in terms of orbital interaction theory (Reid et al. 2002).
The C

H BDE in thiols as a
consequence of the exceptional stability of the radical products due to captoda-
tive stabilization (Viehe et al. 1985; Armstrong et al. 1996). Yet, the observed rate
constants for the reaction of • CH 3 and • CH 2 OH with, e.g., alanine anhydride are
markedly slower than with a thiol. This behavior has been discussed in terms of
the charge and spin polarization in the transition state, as determined by AIM
analysis, and in terms of orbital interaction theory (Reid et al. 2003). With re-
spect to the 'repair' of DNA radicals by neighboring proteins, it follows that the
reaction must be slow although thermodynamically favorable.
Although BDE is by far not the only factor that determines the kinetics of
H-transfer reactions, within a given series of simple alkyl radical a correlation
seems to hold (Table 6.4). In polymers, where the lifetime of the polymer-bound
radicals may be long, radical transfer reactions by intramolecular H-abstrac-
tion (primary

− H BDE in peptides is even lower than that of the S −

tertiary) are common (Chap. 9.4). In general,
whenever a system starts with a mixed radical system (e.g., in the reaction of
• OH with 2-PrOH: 2-hydroxy-prop-2-yl and 2-hydroxypropyl) a steady-state is
approached which is dominated by the lower-energy radical [here: 2-hydroxy-
prop-2-yl, cf. reaction (21)]. This process is favored by low initiation rates and
high substrate concentrations, and these two factors determine whether such an
H-transfer manifests itself is also in the final products.

→ secondary →

As far as DNA is concerned, the most weakly bound hydrogen is the allylic hy-
drogen of the methyl group in Thy. For dGuo, the sequence of the C

− H BDE has

been calculated as C(1 ) (Table 6.5). In DNA, ac-

cessibility as determined by the given structure often overruns factors that are
connected with the R

′ ) < C(4 ′ ) < C(3 ′ ) < C(2 ′ ) < C(5 ′

H BDE (Chap. 12.2).
In DNA, an H-transfer from the methyl group in Thy and from the sugar
moiety to DNA radicals may occur. A well-documented radical that is capable
of reacting with the sugar moiety is the uracil-5-yl radical formed upon pho-
tolysis and radiolysis of 5BrUra-containing DNA (Chaps 10.7 and 12.6). From
Table 6.4, it is seen that this radical is indeed very reactive and thus this kind
of H-abstraction is not unexpected. Steric conditions permitting, it will ab-
stract any hydrogen from the sugar moiety. Less reactive radicals will undergo
such a reaction not only more slowly but also much more selectively (note, for
example, the high kinetic isotope effects of such reactions; • CH 3 + CH 3 OH/
CD 3 OH: k H / k D = 8.2 at 150 °C in the gas phase; Gray and Herod 1968). In DNA,
an H-transfer from the sugar moiety to a base radical has never been proven
with certainty, but in model systems such as poly(U) and poly(C) it is quite evi-
dent (Chap. 11.2). Here, H-transfer is believed to occur from C (2

−

), a position
that in the ribo -polynucleotides is activated by the neighboring OH group. In
DNA, the corresponding hydrogen is bound more strongly.

′