Chemistry Reference
In-Depth Information
Figure 6.25 Bridging oxide and metal hydroxide.
that double Lewis acid activation provides a ca. five orders of magnitude rate accelera-
tion, the oxide should provide ca. six orders of magnitude rate acceleration for the
hydrolysis. Although the dinuclear metal complex provides large rate accelerations
for hydrolyzing phosphate diesters with good leaving groups, it is ineffective for hy-
drolyzing phosphates with poor leaving groups. In this respect, the bridging oxide
behaves like the metal alkoxide (
35
). Neither nucleophile can be deprotonated like
the metal hydroxide (
36
). In contrast to the dinuclear complex with the bridging oxide,
the dinuclear complex with the metal hydroxide (
38
) (Figure 6.25) provides about 11
orders of magnitude rate acceleration for hydrolyzing phosphate diesters with good or
poor leaving groups [120]. Thus, the effect of metal-hydroxide activation and leaving-
group activation are additive. Since metal alkoxides and oxides bridging two metal
centers provide far greater rate acceleration for hydrolyzing phosphates with good leav-
ing groups than for hydrolyzing phosphates with poor leaving groups, synergistic ef-
fect between nucleophile and leaving-group activations is anticipated.
Methyl-p-nitrophenyl phosphate coordinated to the two metal centers in
37
under-
goes hydrolysis by a two-step addition-elimination mechanism [73]. The free phos-
phate hydrolyzes by a concerted mechanism. In both phosphate monoester and diester
hydrolysis, the two Co(
III
) centers in
32
and
37
stabilize the five-coordinate phosphate
species (transition state or intermediate) by bringing the phosphate and nucleophile
together. This stabilization leads to a change in mechanism from dissociative to con-
certed for a phosphate monoester hydrolysis [96] and from concerted to stepwise for
phosphate diester hydrolysis [73].
6.10
Polymerases and DNases
All life forms require polymerases for replication of nucleic acids. DNA polymerases
from various life forms [8] as well as reverse transcriptase fromHIV [9] are all activated
by two metal ions, which are thought to provide three types of activation, i.e. Lewis
acid, metal-hydroxide and leaving group [Figure 6.26(A)]. The Klenow fragment of
DNA polymerase I is a 3
0
,5
0
-exonuclease that is involved in editing the growing
