Chemistry Reference
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Figure 6.17 Double Lewis acid activation.
substitutionally inert; consequently, we have extended our studies with dinuclear
Cu(
II
) complexes (
25
and
26
), which are substitutionally labile (Figure 6.17)
[76-78]. X-ray crystallographic studies reveal that a phosphate can bridge the two metal
centers in both
25
and
26
, as it does in
24
. The intermetal distances in
24
-
26
are about
2.9, 3.6 and 5.0
A
˚
, respectively. Intermetal distances in dinuclear metalloenzymes that
process phosphate esters also range between about 3 and 5
A
˚
[1]. The dinuclear metal
centers in
25
and
26
provide five- to six-orders of magnitude rate acceleration for the
transesterification of 2-hydroxypropyl p-nitrophenyl phosphate and RNA. Based on the
results of studies on cobalt complex
24
and crystal structures and kinetic studies of the
copper complexes, we proposed that the above rate accelerations for the transesteri-
fication reaction are at least in part due to double Lewis acid activation.
The metal hydroxide in
26
may act as an intramolecular general base catalyst for
cleaving RNA. It is unlikely that the metal hydroxide acts as an intramolecular nucleo-
philic catalyst since the 2
0
-hydroxyl group of RNA provides enormous rate enhance-
ment for cleaving RNA. Base-catalyzed cleavage of RNA is about a billion times faster
than base-catalyzed hydrolysis of DNA due to the well positioned nucleophilic group of
RNA [53]. Double Lewis acid activation is expected to provide comparable rate accel-
eration for cleaving RNA and DNA. However, this mode of activation by itself will have
a more significant effect on RNA cleavage. DNA would require nine additional orders
of magnitude rate acceleration to be as reactive as RNA.
6.8
Phosphatase Models
In nature, many enzymes that hydrolyze phosphate monoesters are activated by two or
more metal ions. They include alkaline phosphatase [79], purple acid phosphatase [80],
inositol monophosphatase [81], and
D
-fructose 1,6-biphosphate 1-phosphatase [82].
The active sites of protein serine and threonine phosphatases also consist of dinuclear
