Chemistry Reference
In-Depth Information
Figure 13.6
The TAMEN ligand
Figure 13.7
[Zn(H
2
BHTDE)OH]
3+
and [Zn(quercetin)
2
] complexes
coworkers,
20
which is quite reactive toward plasmid DNA: at pH 7, 50 °C and 3 m M
complex concentration, the supercoiled form of plasmid DNA is completely cleaved
after 24 h, leading to both nicked and linear products. From this data a rate constant
of 4
10
− 5
s
− 1
can be roughly estimated. The cleavage effi ciency shows a maximum
at pH 6.5-7.0, suggesting the possibility that the protonated primary amino groups
play a role in increasing DNA affi nity.
Another interesting example is the [Zn(quercetin)
2
] complex,
21a
(Figure 13.7 ),
which at pH 7.2, 37 °C and 100 mM complex concentration cleaves supercoiled
plasmid DNA with a rate constant of 1.7
×
10
− 4
s
− 1
, which corresponds to a half-life
of about 1 hour. Linearized DNA could be religated with the enzyme T4 ligase,
ruling out the possibility of oxidative mechanisms involving phenoxyl radicals and
confi rming a pure hydrolytic cleavage. Remarkably, the similar Mn(II)-quercetin
complex also shows hydrolytic activity very close to that of the Zn(II) complex
(
k
= 1.3
×
10
− 4
s
− 1
, at pH 7.2, 37 ° C and 100 mM complex concentration).
21b
Because of their redox properties, Cu(II) complexes have been frequently used
in the development of agents for the oxidative cleavage of DNA,
7
but there are also
several examples of Cu(II) complexes reported to cleave DNA with a hydrolytic
mechanism.
Burstyn and coworkers published the fi rst example of a Cu(II)-based hydrolytic
agent in 1996.
22a
It was shown that at a 25 mM concentration the Cu(II)-TACN
complex (Figure 13.8) cleaves supercoiled DNA at 50 °C and pH 7.8 with an
×
