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Non-Enzymatic Biological Catalysis 269
tional acid/base catalysis by the two imidazole groups. The regiospeciWcity of
phosphodiester hydrolysis can be rationalised by the orientation of the aromatic
substrate in the activity, as shown. This system is a very elegant model for
the mechanism of action of ribonuclease A (see Section 5.5).
Many other types of host–guest systems have been developed in recent
years, for example using metal ions to co-ordinate substrate and catalyst
functional groups. One alternative approach with which to Wnish is the use of
polymers to generate chiral cavities containing catalytic groups. The idea of this
approach is to use a small molecule as a template for the co-polymerisation of
regular cross-linked polymer. After polymerisation the template is removed,
leaving a complementary cavity inside the polymer which can bind molecules of
related structure. For example, co-polymerisation of an aromatic dicarboxylic
acid with an amino-acrylamide derivative gives a polymer containing pendant
amino groups contained within cavities inside the polymer, as shown in Figure
12.17. After removal of the template, this polymer was found to catalyse
the b-elimination reaction of a related substrate with enzyme-like Michaelis–
Menten kinetics (K M 27 mm, k cat 1:1 10 2 min 1 ).
In summary, chemists are using rational design and the ability to synthesise
unnatural three-dimensional structures to try to mimic the remarkable catalytic
properties of enzymes, and perhaps to generate new types of catalysts. Such
catalysts might, for example, be able to catalyse new reactions or operate in
organic solvents or at high temperatures. Our current eVorts seem crude compared
with the biological counterparts, but the future holds great promise.
O
CO −
+ H 3 N
2
CO −
2
N
H
O
radical
polymerisation
+ H 3 N
CO −
2
CO −
2
+ H 3 N
N
H
+ H 3 N
diffusion of
‘substrate’
+
H 3 C O
H 3 C O H 3 N
F
H
H 2 N
Figure 12.17 Catalytic polymers.