Ester hydrolysis, catalytic effect

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

In ester hydrolysis, rate-limiting formation of the tetrahedral intermediate usually apphes (Sec. 6.3.1) since the alkoxide group is easily expelled. In contrast, amide hydrolysis at neutral pH involves rate-limiting breakdown of the tetrtihedral intermediate, because RNH is a poor leaving group. The catalytic effect of metal ions on amide hydrolysis has been ascribed to accelerated breakdown of the tetrahedral intermediate. 

The hydrolysis of an ester to alcohol and acid (1) and the esterification of a carboxylic acid with an alcohol (2) are shown here as an example of the Sn2 mechanism. Both reactions are made easier by the marked polarity of the C=0 double bond. In the form of ester hydrolysis shown here, a proton is removed from a water molecule by the catalytic effect of the base B. The resulting strongly nucleophilic OH ion attacks the positively charged carbonyl C of the ester (la), and an unstable sp -hybridized transition state is produced. From this, either water is eliminated (2b) and the ester re-forms, or the alcohol ROH is eliminated (1b) and the free acid results. In esterification (2), the same steps take place in reverse. 

Similarly, vesicular reactivity is dependent on bilayer fluidity and Arrhenius (or Eyring) plots for the decarboxylation of 6-NBIC show a break around Tm. " For the Kemp elimination in different bilayers, it was found that the bilayer for which kinetic data had been gathered below its was least effective as a catalyst. Ester hydrolysis has also been found to be faster above r. For the decarboxylation of 6-NBIC, the increase in catalytic efficiency was attributed to different aggregate surface dynamics based on the observation that vesicles above showed intermediate activation parameters between vesicles below and micelles. One could, of course, discuss causality here considering the fact that many of the bilayer... 

The secondary structure of the polypeptide chain in hydrolytic enzymes ensures the spatial proximity of the necessary functional groups, which are responsible for the observed catalytic effect. In synthetic enzyme mimics, it is possible to bring the requisite functionalities into close juxtaposition only if there is a rigid framework to which these groups are attached. It was thus logical to examine cyclic peptides, especially cyclodipeptides, which bear the necessary functional groups for their catalytic activity in ester hydrolysis. 

The catalytic effect of these cyclodipeptides on substrates having other charged functionalities, in addition to the p-nitrophenyl ester, has been studied (83MI2). The authors were unable to detect any specific catalysis of the hydrolysis of such substrates. 

In a number of classes of systems, the catalytic and other chemical effects of metal ions on reactions of organic and inorganic molecules are generally recognized the catalysis of nucleophilic reactions such as ester hydrolysis the reactions of alkenes and alkynes in the presence of metal carbonyls (8, 9, 69) stereospecific polymerization in the presence of Ziegler catalysts (20, 55, 56) the activation of such small molecules as H2 (37), 02 (13), H202 (13), and possibly N2 (58) and aromatic substitution reactions of metal-cyclopentadienyl compounds (59, 63). 

The ability of metal ions to catalyze the hydrolysis of peptide bonds has been known for 50 years, while the catalytic effect on the hydrolysis of amino acid esters was highlighted in the 1950s. As Hay and Morris point out in their review,76 the major problem with the kinetically labile systems is determining the nature of the reactive complex in solution. Such problems generally do not arise in the more inert systems and consequently reactions involving Co111 have been the more popular for study. 

In order to assess the magnitudes of the catalytic effects of metal ions on the hydrolysis ol a-amino acid esters, it is necessary to have kinetic data on the base hydrolysis of such compounds... 

Succinate esters serve as examples of derivatives that exhibit less than optimal pH-hydrolysis rate behavior owing to their increased reactivity in water as a result of intramolecular catalysis of hydrolysis by the terminal carboxylic acid functionality (Anderson and Taphouse, 1981 Anderson etal., 1984 Damen etal., 2000). Since intramolecular catalytic effects are quite sensitive to geometric factors and distances separating the interactive groups (Anderson and Conradi, 1987), intramolecular catalysis by a terminal ionizable group should be easily controlled by varying the alkyl chain length. 

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 imidazole, but it does not match chymotrypsin, even with the activated unnatural nitrophenyl ester substrate, let alone peptide substrates. 

Micro emulsion droplets and micellar aggregates can catalyse or inhibit chemical reactions by compartmentalization and by concentration of reactants and products. The catalytic effect in micelles has been widely studied, a typical reaction being base catalysed hydrolysis of lipophilic esters. This rate enhancement is normally referred to as micellar catalysis. The analogous effect occurring in microemulsions may be called microemulsion catalysis. 

It should be emphasized that these structural changes within a one-phase region may change the kinetics of a chemical reaction in a pronounced manner. As an example may be mentioned the catalytic effect of Inverse micelles on ester hydrolysis. Fig. 5 is from the first publication — on this subject. It clearly shows the lack of catalytic effect by the premicellar aggregates and the sudden increase of hydrolysis rate in the concentration range where the Inverse micelles begin being formed. 

Oligomeric carbodiimides are useful stabilizers for ester based polymers, such as polyesters, polyester based polyurethanes, polyether based polyurethanes, polyether based poly(urethane ureas) and polycarbonates. The scavenging of carboxyl end groups or carboxyl groups, generated in the hydrolysis of polyesters, with carbodiimide prevents hydrolysis of the polymers caused by the catalytic effect of the carboxyl groups. Neumann... 

Although polyethyleneimine possesses moderate catalytic effects on several hydrolysis reactions, the polymer modified with long allQrl chains show mudi enhanced reactivity toward hydrophobic substrates. Remaikable catalytic effects were observed in the hydrolysis of phenyl esters and a sulfate ester catalyzed by the methylene-imidazole-modified polymer. These results were explained as arising from the hi y brandied, compact stmcture of the polyediyleneimine derivative. Klotz called the imidazole-containing polyethyleneimine synzyme (synthetic enzyme), on the basis of its stmctural characteristics and catalytic activity which are comparable to hydrolytic enzymes. 

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