Chemistry Reference
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12 .9. 5
Transition Metal Desferal Complexes
In the presence of H
2
O
2
and a reductant such as 2-mercaptoethanol, the desferal
complex of Cu(II), Co(III) and Ni(II) cleave plasmid DNA, but the correspond-
ing Fe(II) complex is inactive (Joshi and Ganesh 1992; for the formula of desferal
see Chap. 2.5). This cleavage is inhibited by
•
OH-scavengers such as mannitol.
With the help of synthetic ODNs it has been shown that the Cu(II) desferal com-
plex has only a marginal sequence preference for the cleavage reaction (CG>AT),
while the Ni and Co complexes cleave DNA only at CG sites (Joshi and Ganesh
2004). This clearly indicates that some binding to DNA must occur, and some
suggestions are made in the cited papers (for further studies see Joshi and Ga-
nesh 1994a,b; Joshi et al. 1994).
12 .9.6
Adriamycin
Adriamycin and 11-deoxyadriamycin when complexed to DNA cleave DNA in
the presence of Fe
3+
(Muindi et al. 1984).
Adriamycin is considerably more reactive than its 11-deoxy derivative. The reac-
tive intermediate in this DNA cleavage reaction is thought to be the
•
OH radical.
In order for a Fenton reaction to proceed, Fe
3+
would have to be reduced to Fe
2+
.
No typical reductants are required for this reaction to proceed, and thus adriam-
ycin would have to provide the reduction equivalent, e.g., through its hydroqui-
none moiety. This would be in agreement with the much lower efficiency of the
11-deoxy derivative which lacks a strongly reducing function. The intermediacy
of
•
OH has been concluded from a spin-trapping experiment with DMPO. This
test is, however, not as straightforward as commonly believed, because other
strong oxidants can give rise to the
•
OH-adduct via the DMPO radical cation
(von Sonntag et al. 2004b). Thus, it is well possible that the DNA/adriamycin/
Fe
3+
complex reacts with H
2
O
2
to give an Fe(III)-hydroperoxide. Such an inter-
mediate is made responsible for the site-specific reaction of BLM (Sect. 12.9.2).
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