Chemistry Reference
In-Depth Information
ing no acyl group. Furthermore, k now increases markedly as the acyl group is length-
ened from 2 to 12 carbons (Table 3.1). For nitrophenyl laurate, k with lauroyl-polyethy-
lenimine is 10
4
times greater than that with propylamine. Such a comparison may not
be fully appropriate if the low rate with the reference amine is due primarily to the
micellar state of the lauroyl nitrophenyl ester. If one assumes that in the absence of
micelle formation the long-chain ester would show a rate comparable to that of acetyl
nitrophenyl ester, the enhancement factor in the presence of lauroyl-polyethylenimine
is still of the order of 10
3
. In any event, the introduction of strong binding sites on the
polymer clearly leads to marked rate enhancements.
3.2.3
Polyethylenimines with Nucleophile Adducts
Having polymers with strong ligand binding abilities, and with capacities to accelerate
rates, one can graft onto the macromolecular matrix truly catalytic functional groups.
The imidazole moiety is an attractive, well-recognized nucleophile (particularly effec-
tive in model systems) in catalyzing the hydrolysis of nitrophenyl esters (Eq. 2).
With a polyethylenimine containing 10% of its residues alkylated with dodecyl
groups and 15% alkylated with methyleneimidazole substituents, esterolysis is truly
catalytic [16]. Table 3.2 compares the catalytic effectiveness of this polymer biocatalyst
(synzyme) with that reported for other substances that accentuate nitrophenyl ester
hydrolysis [17, 18]. Clearly, this polymer is nearly 300 times as effective as free imi-
dazole, but it does not match chymotrypsin, even with the activated unnatural nitro-
phenyl ester substrate, let alone peptide substrates.
Nucleophiles other than imidazole have also been coupled to polyethylenimines and
other polymers. These include hydroxamate [19-23], mercaptan [24, 25], aldoxime [26],
and triazine [27] functionalities. In general, these moieties are active in transferring
the acyl group of nitrophenyl esters to the nucleophile, but deacylation of the acylnu-
cleophile is slow.
Conversely, dimethylaminopyridines attached to polymers are remarkably effective
catalysts of the solvolysis of esters, with true turnover [28-30].
Pyridine itself attached to polyethylenimines (through a reduced Schiff base linkage)
shows no catalysis, evidently because in the polymer environment both the pK
a
and
nucleophilicity of the ring nitrogen are reduced substantially. However, 4-N,N-dialky-
Table 3.2 Relative effectiveness of various catalysts in cleavage of nitrophenyl esters.
Catalyst
Catalytic Constant k
(
M
-1
min
-1
)
10
a
Imidazole
-Chymotrypsin 10 000
b
PEI-600, 10% dodecyl. 15% imidazole groups 2700
a)
Substrate was p-nitrophenyl acetate, at a pH near neutrality. Taken from Ref. 17.
b)
Taken from Ref. 18.
a
