Chemistry Reference
In-Depth Information
6A,6C and 6A,6D isomers (the seven glucose units of the cyclodextrin are labeled A
through G). (As described below, we were later able to prepare as pure catalysts all the
isomers of the bis-imidazole cyclodextrin with the imidazole rings on the primary car-
bons of the ring. The geometric dependence of catalysis indicated the mechanism
involved.)
On examining this catalyst mixture in the hydrolysis of the cyclic phosphate of
4-t-butylcatechol
36
, we saw a bell-shaped pH rate profile, indicating bifunctional
acid-base catalysis of the hydrolysis as in the enzyme ribonuclease. A catalyst carrying
only one imidazole showed only base catalysis, by the unprotonated imidazole group
Im. Thus, in catalyst mixture
41
, one imidazole was acting as a base - delivering a
water molecule to the phosphate group of the bound substrate - while the imidazo-
lium ion of the other catalytic group played a role as a general acid. At the time we
thought that this imidazolium ion might be simply protonating the leaving group of
the phosphate, as was normally assumed for the enzyme ribonuclease A, but our later
work revealed a more interesting role.
Simple hydrolysis of substrate
36
with base in solution furnishes an essentially equal
mixture of
37
and
38
, since the t-butyl group is too remote to have any influence. How-
ever, catalysis by the artificial enzyme mixture
41
gave
37
only. The geometry of the
catalyst-substrate complex directs the attack by water (hydrogen bonded to the imi-
dazole) in a line perpendicular to the ring axis (cf.
42
). When we moved the two imi-
dazole groups out further, in catalyst
43
, they were then able to deliver the water in a