Chemistry Reference
In-Depth Information
Figure 13.14
Intercalator-metal binding unit conjugates reported by Schneider (a), Naka-
mura (b) and Tonellato (c)
free metal ion, but to a decrease in the DNA affi nity. Finally, an earlier report by
Nakamura and Hashimoto,
40
which investigated the reactivity of a hydroxamic acid
linked to a phenanthridine intercalator (Figure 13.14b) in the presence of different
lanthanide ions, points attention to the length of the spacer that tethers the inter-
calating unit to the catalytic group as a key element for cleavage activity.
This result is confi rmed by the reactivity of a series of Zn(II)-
cis - cis
- triaminocy-
clohexane complex-anthraquinone intercalator conjugates, linked by alkyl spacers
of different length, reported by Tonellato and coworkers (Figure 13.14c).
41
At a
concentration of 5 mM, the complex of the derivative with a C
8
alkyl spacer cleaves
supercoiled DNA with a rate of 4.6
10
− 6
s
− 1
at pH 7 and 37 °C. Saturation kinetics
have been observed with a binding constant (
K
a
) of about 1
×
10
4
M
− 1
, in agreement
with the reported DNA affi nity of anthraquinone. Thus, the conjugation of the metal
complex with the intercalating group led to a 15-fold increase in the cleavage effi -
ciency when compared with the Zn-triaminocyclohexane complex lacking the
anthraquinone moiety. Comparison of the reactivity of the different complexes
showed a remarkable increase in DNA cleaving effi ciency due to the increase in the
spacer length. In the case of the shortest spacer (C
4
) no cleavage was observed,
indicating that the advantages derived by the increased DNA affi nity may be can-
celled out by incorrect positioning of the reactive group.
A recent example of a DNA-intercalating Zn(II) complex has been described
by Yang and coworkers,
42
who studied the reactivity of the Zn[(phen)(dione)Cl]ClO
4
complex (Figure 13.15) toward pBR322 plasmid DNA. In this case the ligand itself
is able to intercalate DNA with a binding constant of 2.4
×
10
4
M
− 1
and the cleavage
×
10
− 5
s
− 1
at pH 8.1, 37 °C and a 3.0 mM complex
concentration. The observed rate constant is relatively high, but it has to be taken in
account that it has been obtained at high complex concentration. Due to the nature
of the ligand, a direct comparison with a nonbinding complex is not possible, but the
authors report that other complexes made by Zn
2+
and phenanthroline are not active.
proceeds with a rate constant of 5.8
×
