Chemistry Reference
In-Depth Information
siderably lower than that of water bound to free zinc ion (8.96). There has been much
interest in developing simple zinc hydrate complexes with neutral pK
a
s. Woolley
reported a five-coordinate zinc hydrate complex (
2
) with a pK
a
of 8.7 [30, 31]. This
complex was shown to be active for catalyzing the hydration of carbon dioxide. Kimura
et al. reported a tetrahedral zinc hydrate complex (
3
) with a pK
a
(7.3) [32] that closely
matches that of the zinc hydrate at the active site of carbonic anhydrase. Kimura's
complex was a good catalyst for hydrolyzing esters with good or poor leaving groups.
Ligands can be designed to influence the acidity of the metal center in several ways.
Metal ions with fewer coordinated ligands should be more acidic (Figure 6.2). Thus,
tetrahedral zinc should be more acidic than five- or six-coordinate zinc. Decreasing the
basicity of the ligand should increase the Lewis acidity of the metal center. Electron-
withdrawing groups attached to ligands should, therefore, enhance the acidity of the
metal. Steric effects or strain could also be used to weaken the metal-ligand interac-
tion. The equilibrium constant for binding of the twelve-membered ring macrocycle to
zinc (
3
) is about a hundred times smaller than that for binding of the eleven-mem-
bered ring macrocycle to zinc (
4
) [32]. The hundred-fold weaker binding of the triaza
ligand in
3
appears to translate to a ten-fold increase in acidity of the metal-bound
water (pK
a
of
4
is 8.2). While tight binding of the ligand to the metal is desirable
to form a stable complex, weak binding is needed to enhance the Lewis acidity of
the metal. In
3
and
4
, the equilibrium constant for binding of the macrocyclic ligand
to the zinc ion is large (when compared to the binding of linear ligands to the metal
ion) yet the three nitrogens in
3
are held sufficiently apart from the metal by strain. The
weak interaction between the nitrogens and zinc ion in
3
results in increased acidity of
the metal ion.
Hydrolytic metalloenzymes can provide enormous rate accelerations for hydrolyz-
ing a wide variety of substrates [1-3]. It is an interesting challenge to be able to
determine how much rate acceleration is possible due to Lewis acid activation alone.
An upper limit to the rate acceleration due to Lewis acid activation could be obtained
from the change in acidity of water upon coordination to a metal ion (Table 6.1). For
example, if a metal ion increases the acidity of the water molecule by a million-fold,
this metal ion should provide up to a maximum of a million-fold rate acceleration for
hydrolysing esters (or amides, nitriles or phosphates; Figure 6.1). A greater charge
buildup on the coordinated oxygen is anticipated on going from the metal-bound water
Figure 6.2 Acidity of zinc-bound water.
