Chemistry Reference
In-Depth Information
When functional groups are attached to the cyclodextrin ring, new artificial enzymes
can result. We have already described this for the attachment of thiazolium rings and
pyridoxamine/pyridoxal rings above, and will describe the attachment of metal cata-
lytic groups in the next section. However, one study with attached phosphate groups
addressed a general question: Is there a preference for putting such groups on the
primary or secondary side of the cyclodextrin ring [93]? In the studies mentioned
to this point, the catalytic groups were attached to the primary CH
2
groups of the cy-
clodextrins, but the acylation reaction occurred on the secondary CH-OH groups.
We prepared phosphate esters
13
and
14
of both the secondary hydroxyl and primary
hydroxyl groups of
-cyclodextrin, and examined them as general acid and general
base catalysts for the reactions of bound substrates [93]. The phosphate anion acted
as a general base to catalyze enolization and the resulting hydrogen exchange in a
bound tritiated phenacyl ketone
15
when the phosphate was either primary or second-
ary, showing that the substrate can bind equally well and undergo catalysis when
pointed in either direction in the cyclodextrin cavity. However, the general acid-cat-
alyzed hydrolysis of a bound acetal
16
had a preference for the phosphoric acid group
on the secondary side. The position of attachment of the catalytic groups can be im-
portant.
b
1.3.2
Metalloenzyme Mimics
Chymotrypsin is only moderately effective as an enzyme, and much higher rates are
seen with metalloenzymes. Zinc is especially important in such hydrolytic enzymes
(cf. Ref. 94). For example, the enzyme carboxypeptidase A uses zinc in a typical bi-
functional role, at the same time activating a carbonyl for addition by coordinating
with its oxygen and activating a water molecule to act as a nucleophile [95-100].
We produced a model for this type of process by using metal complexing as the sub-
strate binding force and a coordinated oxime as the nucleophile (
17
) [101]. The geo-
metry of this compound means that the Lewis acidic zinc and the basic oxime anion
can co-exist without quenching each other; the electrons can flow from one to the other
only through the bridging carbonyl group of the substrate (
18
). Consequently, the an-
ion of
17
reacted with metal-bound substrate
19
to transfer the acetyl group to the
oxime anionic oxygen, and then the intermediate
20
rapidly hydrolyzed. In this process
the metal ion is serving multiple functions; it binds the substrate, acidifies the oxime,
