Chemistry Reference
In-Depth Information
group - is like both that in the enzyme carbonic anhydrase and the one we proposed
for histone deacetylase [114, 115]. In those enzymes Zn
2+
is the catalytic metal ion.
We have pursued such ester hydrolysis by artificial enzymes further. With a cyclo-
dextrin dimer related to
25
we have hydrolyzed an ordinary doubly bound ester, not
just the more reactive nitrophenyl esters [116], with catalytic turnovers. Also, with a
catalyst consisting of a cyclodextrin linked to a metal ligand carrying a Zn
2+
and its
bound oxime anion, we saw good catalyzed hydrolysis of bound phenyl esters with
what is called burst kinetics (fast acylation, slower deacylation), as is seen with
many enzymes [117].
Artificial enzymes with metal ions can also hydrolyze phosphate esters (alkaline
phosphatase is such a natural zinc enzyme). We examined the hydrolysis of p-nitro-
phenyl,diphenylphosphate (
29
) by zinc complex
30
, and also saw that in a micelle the
related complex
31
was an even more effective catalyst [118]. Again the most likely
mechanism is the bifunctional Zn-OH acting as both a Lewis acid and a hydroxide
nucleophile, as in many zinc enzymes. By attaching the zinc complex
30
to one or two
cyclodextrins, we saw even better catalysis with these full enzyme mimics [119]. A
catalyst based on
25
- in which a bound La
3+
cooperates with H
2
O
2
, not water - accel-
erates the cleavage of bis-p-nitrophenyl phosphate by over 10
8
-fold relative to uncata-
lyzed hydrolysis [120]. This is an enormous acceleration.
Phosphate ester cleavage can also be achieved with artificial enzymes using both a
metal ion and an additional catalytic group, as in the amide and ester hydrolyses de-
scribed above. In our first example, catalysts
32
and
33
combined a Zn
2+
with a thio-
phenol and an imidazole group respectively [121]. The rigid structure prevented the
