Chemistry Reference
In-Depth Information
Figure 6.1
Lewis acid activation for hydrolysis and other organic reactions.
some metal-bound water molecules [26]. Metal cations increase the acidity of the
bound water molecule by stabilizing the metal-bound hydroxide anion. Here again,
the role of the metal ion is oxyanion stabilization (Figure 6.1). Calcium ions increase
the acidity of the free water molecule almost a thousand-fold while zinc ions increase
the acidity almost ten million-fold. The stronger the Lewis acidity of the metal ion, the
lower is the pK
a
of the bound water molecule (Table 6.2). Hydronium, or water bound
to proton, is far more acidic than water bound to Zn(
II
) [water bound to highly Lewis
acidic metal ions such as Ti(
IV
) is expected to be more acidic than hydronium]. Pro-
tonated substrates are expected to be far more reactive to hydrolysis than the corre-
sponding substrates coordinated to metal ions in Table 6.2. However, metal ions can
provide greater activation than proton through cooperative interaction of Lewis acid
activation and nucleophile activation.
The active site of bovine carbonic anhydrase consists of a tetrahedrally coordinated
zinc ion (
1
) [27] with a coordinated water molecule whose pK
a
(7.5) [28, 29] is con-
Table 6.2 Acidity of free and metal ion or proton bound water molecules.
Water species
pK
a
H
2
O
15.72
Ca(
II
)-OH
2
12.85
Mg(
II
)-OH
2
11.44
Mn(
II
)-OH
2
10.59
Co(
II
)-OH
2
10.2
Ni(
II
)-OH
2
9.86
Fe(
II
)-OH
2
9.5
Zn(
II
)-OH
2
8.96
H
3
O
+
-1.72
