Chemistry Reference
In-Depth Information
Figure 13.8
Structures of some polyamine ligands used for the formation of mononuclear
Cu(II) complexes active in DNA cleavage
estimated rate constant of ca. 1.5
10
− 5
s
− 1
. A decrease of reactivity was observed at
higher complex concentrations probably due to the formation of unreactive m -
hydroxo dimers.
22b
The complex is also active in the degradation of single-stranded
DNA. However, anaerobic experiments showed that the activity in the absence of
oxygen is reduced by 30%, indicating at least the simultaneous occurrence of both
hydrolytic cleavage and oxidative cleavage.
Later on, Fujii and coworkers reported that the Cu(II)-TACH complex (Figure
13.8) promotes the oxygen-independent cleavage of plasmid DNA.
23a
Saturation
kinetics were observed with a
k
max
value of 1.2
×
10
4
M
− 1
at 35 °C and pH 8.1. Such reactivity is among the highest reported so far and corre-
sponds to a half-life time for the supercoiled form of 20 minutes in the presence of
75 mM Cu(II) complex. Several other complexes of macrocyclic and linear triamine
ligands were tested and found to be scarcely reactive. On the basis of these results
and of the relatively good affi nity of the Cu(II)-TACH complex for DNA, the
authors suggest the possibility of specifi c binding of the catalyst to the substrate. A
detailed analysis of complex speciation and pH reactivity profi les indicate that the
monohydroxo complex is the active species at pH values above neutrality, as
observed in the hydrolytic cleavage of model phosphate diesters.
23b
However, linear-
ized plasmid DNA could not be enzymatically religated.
23b
Similar results have also
been obtained for the related Cu(II)-TACI complex (Figure 13.8), which again
shows an oxygen-independent activity (
k
= 2.3
×
10
− 3
s
− 1
and a
K
a
value of 1.3
×
×
10
− 3
s
− 1
at 48 mM complex concen-
tration), but fails the enzymatic religation test.
24
A pure hydrolytic mechanism, demonstrated both by oxygen-independent
activity and enzymatic religation, characterizes the activity of the Cu(II) complexes
of natural aminoglycosides, such as neamine (Figure 13.8) studied by Cowan and
coworkers.
25
With the Cu(II)-neamine complex, saturation kinetics were observed
with a
k
max
value of 5.2
10
5
M
− 1
at 37 ° C and pH 7.3.
The very high affi nity of the complex for DNA is attributed to the tight binding of
the positively charged aminoglycoside ligand to DNA; this apparently makes the
system very effective even at low concentrations, reducing the half-life time for the
×
10
− 4
s
− 1
and a
K
a
value of 2.4
×
