Chemistry Reference
In-Depth Information
Cytochrome P-450 can perform both intramolecular and intermolecular nitrene in-
sertions with
106
in water solution [181]. However, the intermediate metallo-nitrene
(
108
) also hydrolyzed to some extent; so the enzyme performed a hydroxylation as well
as an amidation. Although we have also performed an intermolecular amidation of a
steroid, using such a metalloporphyrin reaction with
106
to form
112
[182], we have
not yet extended it to the kinds of directed functionalizations described above with
either benzophenones or chlorinations.
1.4.5
Binding by Cyclodextrin Dimers
To create artificial enzymes that could bind substrates in water solution with defined
geometry, we examined dimers of cyclodextrins. As mentioned above, we used such
dimers in mimics of hydrolytic enzymes [119, 120]. Now we wished to use them for
mimics of cytochrome P-450.
Initially, we prepared
-cyclodextrin dimers
113
-
116
[183], which were examined for
substrate binding with two p-t-butylphenyl groups. With ester
117
and cyclopropene
118
we saw binding constants as high as 10
8
M
-1
. This is double the free energy of
binding of simple p-t-butylphenyl groups into a single cyclodextrin - binding constants
are generally about 10
4
M
-1
- so the free energies of binding were additive with sub-
strates that could fit well.
Even stronger dimeric binding, due to the entropy advantages of chelate binding,
was seen with cyclodextrin dimer
119
, which was doubly linked, restricting its rota-
tional freedom [184]. The flexible substrate
120
gave a binding constant to dimer
119
of
10
10
M
-1
, while with the rigid substrate
121
the binding constant was even larger. In-
terestingly, although the arguments for special effects in chelate binding normally
involve entropy advantages, a study we did of several such chelate binding situations
b
