Esterolytic catalysts

Typical antibody-catalyzed reaction rates are several hundredfold to 100,000-fold faster than the uncatalyzed reaction of the substrate. Several fundamental postulates have been proposed to explain the rate enhancements that nevertheless fall short of the enormous rate accelerations of enzymes. Is activity truly due solely to transition state stabilization by antibody-binding interactions Can additional binding interactions be built into the combining site or into the substrate molecule itself to increase the overall rate of the reaction Can new screening methods and immunological methods be developed to uncover novel catalysts with diverse activities Most important, can novel esterolytic catalysts be developed based on currently available catalytic antibody technology to efficiently hydrolyze and detoxicate cocaine ... 

Nucleophiles such as imidazole, pyridine (Letsinger and Savereide, 1962), and hydroxylamine are known to be powerful catalysts of ester hydrolyses. An extensive study of polymeric analogs of these compounds has shown that they too act as effective esterolytic catalysts (Overberger et aL, 1965 Overberger and Smith, 1975). The topic has been reviewed (Overberger and Salamone, 1969 Morawitz, 1969 Manecke and Storck, 1978 Overberger et aL, 1978) and only important features of these polymeric catalysts will be discussed here. 

The copolymer of A -vinylimidazole and acrylic acid has been found to be an effective esterolytic catalyst for the hydrolysis of p-nitrophenyl acetate (Letsinger and Klaus, 1964 Shimidzu et al., 1974). The carboxyl groups in this polymer can bind a positively charged substrate, e.g. (3). Thus, the catalytic esterolytic activity of such a polymer for the positively charged 3, the neutral 4 and the negatively charged 5 is in the order ... 

Reactions on macromolecular precursors are most often the key step in the synthesis of sophisticated polymers in various well documented fields of steadily increasing importance such as a) linear or crosslinked polymeric reagents and catalysts (2,5,6, 49) b) polymers showing esterolytic enzyme-like properties (2, 49-52) c) polymeric drugs (53.54) and so on... Three more specific but still highly significant studies are outlined below. 

Several reviews have been published describing our work on imidazole catalysis.(1-4) Other investigators in this field have published comprehensive review articles comparing synthetic catalysts to enzymes.(5-91 The esterolytic activity of the three catalyst systems reviewed in this paper have been compared to poly[4(5)-vinylimidazole] (PVIm) in 28.5% ethanol-water solutions since PVIm is not soluble in water. However, within each system, minor changes in catalyst apolarity illustrate the effect of hydrophobic interactions on the rate of esterolysis. The substrates consisted of a series of neutral j -nitrophenyl esters (Sn) and negatively charged 4-acyloxy-3-nitrobenzoic acids (Sn ), where n denotes the number of carbons in the acyl chain. 

Copolymerization of 4(5)-vinylimidazole with vinylamine increased the water solubility of the catalyst and, therefore its esterolytic activity.(15) Copoly[4(5)-vinylimidazole-vinylamine] (II) had considerably lower pKa values for the imidazole residues in water (5.11-5.40) than the imidazole residues for PVIm in 28.5% ethanol-water (5.78-6.20).(14) Apart from the difference in solvent, the polyelectrolyte effect from the strongly basic amine residues (pKa 7.35-7.74 in water) was responsible for the lower pKa values. 

Esterolytic Reactions of Active Esters Using Heterogeneous Polymeric Catalysts Containing Imidazole Groups... 

More recently, we turned our attention toward insoluble pol)rmer catalysts to provide additional insight into this area. This article describes the synthesis of insoluble polymeric catalysts and substrates and a preliminary study on their esterolytic reactivity towards various long-chain p-nitrophenyl esters. 

Table 2. Comparison of esterolytic efficiencies of natural and abiotic molecular catalysts...

The azacyclophane 18 is built according to the same general pattern which has been successfully applied in the construction of esterolytic octopus-like molecular catalysts The design features and catalytic properties of functionalized octopus cyclophanes 22 and related structures have been reviewed in depth recently... 

Ohkubo, K. Funakoshi, Y. Urata, Y. Hirota, S. Usui, S. Sagawa., T. High Esterolytic Activity of a Novel Water-Soluble Poljmer Catalyst Imprinted by a Transition-State Analogue. J. Chem. Soc., Chem. Commun. 1995, 20, 2143-2144. 

It has been recognized a long time ago that hydrolytic enzymes can behave as any other catalyst and catalyze the reverse reaction condensation (1,2). It is then possible to use simple enzymes with esterolytic activity, not requiring cofactors, such as esterases, lipases, or some proteases, to synthesize ester bonds, as long as the thermodynamic conditions required to favor this reaction are not detrimental to the activity of the enzyme. This last point is of great importance since most enzymes have evolved to operate in aqueous media, and not in the conditions necessary to foster condensation, for example, low water and high acid and/or... 

Polymeric imidazole catalysts are the synthetic prototype of esterolytic enzymes because, like the enzymes, they have binding centers for the substrate as well as for the catalytic groups. In case of the homopolymer, polyvinylimidazole, the partially protonated groups can act as binding sites, provided the substrate is negatively charged. Thus at pH 7.5, when... 

This review article summarizes our more recent investigations of the esterolytic action of water soluble imidazole containing polymers. In our previous work we have explained increased reactivity of polymeric reactants in terms of electrostatic and cooperative effects. Recently, we have directed our efforts in emphasizing the apolar interaction as it has reflected dramatic rate enhancements and proven a predominant factor in determining the maximum catalytic efficiency. Polymeric catalysts which are included in this review are poly[l-alkyl-4(5)-vinyl-imidazoles] and their copolymers, hydro-phobic terpolymers of 4(5)-vinylimidazole, copoly[vinylamine/4(5)-vinylimidazole], and poly(ethylenimine-g L-histidine). All of these catalysts share the common property of water solubility and the capability of attaining high catalytic efficiencies which is attributed to apolar interactions. 

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