Chemistry Reference
In-Depth Information
Figure 6.12 Four-membered ring transition state analog at the active
site of carboxypeptidase A.
Dinuclear metal complexes have been used to combine Lewis acid and nucleophile
activations. For nitrile hydration, Lewis acid activation alone can provide a ca. 10
6
-fold
rate acceleration (Figure 6.4) and a well-positioned metal hydroxide can provide an-
other 10
9
-fold rate enhancement (
8
,
9
). Sargeson et al. [58] found that joint Lewis ac-
tivation and nucleophile activation with a dinuclear Co(
III
) complex (
16
) provides an
amazing 10
15
-fold rate acceleration over the background hydroxide rate for the hydra-
tion reaction (Figure 6.13). Thus, Lewis acid and hydroxide activations appear to be
additive (10
6+9
=10
15
). The greater reactivity of the dinuclear system (
16
) over the
mononuclear system (
13
) is probably due, mainly, to the better positioning of the metal
hydroxide in
16
.In
13
, hydration is accompanied by formation of a strained four-mem-
bered ring transition state, whereas in
16
nucleophilic attack of the metal hydroxide on
the coordinated nitrile affords a six-membered ring transition state. Rapid hydrolysis
of an amide by joint Lewis acid and nucleophile activations has also been accomplished
with a dinuclear metal complex (Figure 6.13,
17
) [59].
There has been prolonged interest in developing catalysts or reagents that cleave pro-
teinmolecules sequence specifically for their potential in the study of proteins as well as
in the generation of a new class of therapeutic agents [60-62]. Sequence specific hydro-
lysis of proteins and oligopeptides has been achieved by combining Lewis acid activa-
tion and nucleophile activation using Pd(
II
) [63] and Co(
III
) complexes [64].
Figure 6.13 Joint Lewis acid activation and nucleophile activation
with dinuclear metal complexes.
