Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 246

The 5,6-dihydrothymid-5-yl radical has been produced independently by
photolyzing an adequately substituted derivative (Barvian and Greenberg 1995).
This radical has a rather low H-abstracting power, and very good H-donors such
as 1,4-dihydrocycloexadiene are required to afford substantial yields of H 2 Thd
beyond simple disproportionation. The latter has been shown to proceed both by
H-transfer to C (5) as well as to O (4). In the case of the dinucleotide dUrdpThd,
the 5,6-dihydrothymid-5-yl abstracts the C (1

H of the neighboring dUrd unit
[reaction (145); Tallman and Greenberg 2001]. The rate constant for this intra-
molecular H-transfer has been estimated to range between 115 and 400 s − 1 . In
the presence of O 2 , an interesting selective intramolecular C (1

′ ) −

H abstraction
by the 5 S -diastereoisomer of the C (5) peroxyl radicals takes place. This leads to
a damage amplification (tandem lesion) with a 2

′ ) −

′ dRL and a 5OOH6HThy lesion

[reactions (147)-(149)].

The 5,6-dihydro-2 -deoxyuridin-6-yl was generated specifically by photolyz-

ing the respective tertiary butyl ketone (Carter and Greenberg 2003). It reacts
fast with 2-mercaptoethanol [reaction (150); k = 8.8

′

10 6 dm 3 mol −1 s −1 ] and
noticeably slower with 2,5-dimethyltetrahydrofurane (31 dm 3 mol − 1 s − 1 ). In the
presence of O 2 , 6-hydroxy-5,6-dihydro-dUrd is the major product [reactions
(151) and (152)]. Interestingly, 2-dRL is also formed under such conditions
which is believed to be formed by an intramolecular C (1

×

H abstraction via a
six-membered transition state [reaction (153); for this type of reaction see also
Chap. 8.6].

′ ) −