Hydrolysis of activated esters

Co-existence curves of the A-poly-2 copolymer before and after the hydrolysis of active ester groups indicated that, in both water and PBS, the copolymer with intact active esters had an LCST a few degrees lower (29 a 31 C) than that of the hydrolyzed copolymer (31 a 34 C). 

Most of the pseudounimolecular hydrolytic probe reactions involve water-catalyzed pH-independent hydrolysis of activated esters, amides, or acid chlorides " " (Scheme 9). The hydrolysis of these probes occurs via a dipolar... 

Hydrolysis of activated esters of a-amino acids or acetylcholine analogs catalysed by Cu or Zn modified with the tenside ligands 118,119 and 120 (Table... 

Buckingham, D. A., and C. R. Clark, Metal-hydroxyde-promoted hydrolysis of activated esters. Hydrolysis of 2,4-dinitrophenyl acetate and 4-nitrophenyl acetate , Aust. J. Chem., 35,431-436 (1982). 

Antibody 48G7, elicited with p-nitrophenyl phosphonate 1, is a representative esterase [12], It accelerates the hydrolysis of activated ester 2a and carbonate 2b by factors of >104 (Scheme 4.1). Detailed study of its structure and immunological origins has provided valuable insight into the mechanism and evolution of catalysis. 

As described in a previous section, the imidazole group of a histidyl residue is involved in a most direct fashion in the catalytic action of hydrolytic enzymes (see Table 2—1). This fact attracted mudi attention among phyrical organic chemists, and imidazole and imidazole compounds became the first organic bases to have been established as catalysts for ester hydrolysis. Since the weakly basic imidazolyl group is not capable of directly displacing the much mtxe basic alkoxide ions from normal esters, most studies have dealt with the catalysis of the hydrolysis of activated esters, such as phenyl acetates and thiol esters ... 

Russell et al. [43] studied lipase-catalyzed polymerizations of activated diesters and fluorinated diols. The effects of reaction time, continuous enzyme addition, enzyme concentration, and diol chain length were studied to determine factors that might limit chain growth. Potential limiting factors considered were enzyme inactivation, enzyme specificity, reaction thermodynamics, hydrolysis of activated esters and polymer precipitation. The polymer molecular weight at 50°C steadily increased and then leveled off after 30h at Mw 1773. 

The NH group in the imidazole nucleus of the histidine side chain has often been left unprotected with no obvious detriment to the procedure or the product of the synthesis. Some side reactions, however, can be attributed to the effect of imidazole. It acts as catalyst in the (undesired) O-acylation of serine and tyrosine side chains and also, if water is not excluded from the medium, in the hydrolysis of active esters. Furthermore, because the basic character of the imidazole is weak but not negligible, histidine containing peptides are sometimes isolated in more than one form, for instance as the base and the trifluoro-acetate or as the mixture of the hydrochloride and the acetate, etc. Therefore, masking of the imidazole offers certain advantages. 

There are, however, other binding forces that might be used to hold a, for example, nonionic substrate in a cavity. One such possibility that has been investigated is the use of hydrophobic interactions . This can be illustrated with an example. The macrocycles (34) and (55) obtainable by means of acyloin condensation, followed by conversion to the oxime, possess functionalities that are potential catalysts for the hydrolysis of activated esters. If hydrophobic interactions are important, an activated ester of a long chain fatty (i.e. hydrophobic) acid, for example, the p-nitro-phenolate ester of lauric acid, should associate in water with the hydrophobic... 

Brown RA (1962) The linear enthalpy-entropy effect. J Org Chem 27 3015-3026 Buckingham DA, Clark C (1982) Metal-hydroxide promoted hydrolysis of activated esters. Hydrolysis of 2,4-dinitrophenylacetate and 4-nitrophenylacetate. Aus J Chem 35 431-436... 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

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... 

Nitrocellulose is among the least stable of common explosives. At 125°C it decomposes autocatalyticaHy to CO, CO2, H2O, N2, and NO, primarily as a result of hydrolysis of the ester and intermolecular oxidation of the anhydroglucose rings. At 50°C the rate of decomposition of purified nitrocellulose is about 4.5 x 10 %/h, increasing by a factor of about 3.5 for each 10°C rise in temperature. Many values have been reported for the activation energy, E, and Arrhenius frequency factor, Z, of nitrocellulose. Typical values foiE and Z are 205 kj/mol (49 kcal/mol) and 10.21, respectively. The addition of... 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Hydrolysis of Enol Esters. Enzyme-mediated enantioface-differentiating hydrolysis of enol esters is an original method for generating optically active a-substituted ketones (84—86). If the protonation of a double bond occurs from one side with the simultaneous elimination of the acyl group (Fig. 3), then the optically active ketone should be produced. Indeed, the incubation of l-acetoxy-2-methylcyclohexene [1196-73-2] (68) with Pichia... 

Table 7 Activation Parameters for the Resin Catalyzed Hydrolysis of Some Esters in Water-Solvent Mixtures...

Esterases have a catalytic function and mechanism similar to those of lipases, but some structural aspects and the nature of substrates differ [4]. One can expect that the lessons learned from the directed evolution of lipases also apply to esterases. However, few efforts have been made in the directed evolution of enantioselective esterases, although previous work by Arnold had shown that the activity of esterases as catalysts in the hydrolysis of achiral esters can be enhanced [49]. An example regarding enantioselectivity involves the hydrolytic kinetic resolution of racemic esters catalyzed by Pseudomonasfluorescens esterase (PFE) [50]. Using a mutator strain and by screening very small libraries, low improvement in enantioselectivity was... 

Procarboxypeptidase A is activated by the removal of a peptide of some 64 residues from the N-terminus by trypsin.153 This zymogen has significant catalytic activity. As well as catalyzing the hydrolysis of small esters and peptides, procarboxypeptidase removes the C-terminal leucine from lysozyme only seven times more slowly than does carboxypeptidase. Also, the zymogen hydrolyzes Bz-Gly-L-Phe with kcsA = 3 s-1 and KM = 2.7 mM, compared with values of 120 s 1 and 1.9 mM for the reaction of the enzyme.154 In contrast to the situation in chymotrypsinogen, the binding site clearly pre-exists in procarboxypeptidase, and the catalytic apparatus must be nearly complete. 

Amino acid esters act as chelates to Co111 for example, the /3-alanine isopropyl ester is known as both a chelate and as an /V-bonded monodentate,983 and the mechanism of hydrolysis of the ester, which is activated by coordination, to yield chelated /3-alanine has been closely examined. 

Fungal cutinase catalyzes hydrolysis of model substrates and in particular p-nitrophenyl esters of short chain fatty acids, providing a convenient spectro-photometric assay for this enzyme activity [101,102,116]. Hydrolysis of model esters by this cutinase showed the high degree of preference of this enzyme for primary alcohol ester hydrolysis. Wax esters and methyl esters of fatty acids were hydrolyzed at low rates. Alkane-2-ol esters were hydrolyzed much more slowly than wax esters and esters of mid-chain secondary alcohols were not... 

In a different approach three different structurally defined aza-crown ethers were treated with 10 different metal salts in a spatially addressable format in a 96-well microtiter plate, producing 40 catalysts, which were tested in the hydrolysis of /xnitrophenol esters.32 A plate reader was used to assess catalyst activity. A cobalt complex turned out to be the best catalyst. Higher diversity is potentially possible, but this would require an efficient synthetic strategy. This research was extended to include lanthanide-based catalysts in the hydrolysis of phospho-esters of DNA.33... 

Optically active 3-hydroxybutanoic acid and its methyl ester were first prepared by McKenzie, Magnus-Levy, and Emil Fischer.3 The biopolymer PHB and mixed polymers containing (R)-3-hydroxybutanoate and (R)-3-hydroxypentanoate were also discovered long ago,4 5 and are now produced on an industrial scale. .7 As described here, depolymerization by transesterification [H+ or Ti(OR)4 catalysis], or by hydrolysis, produces8-9 the corresponding monomeric (R)-esters and (R)-acids 1. The 3-hydroxybutanoic acid can also be prepared by hydrolysis of the ester.2-10... 

These relations both demonstrate the inhibition of formation of the tetrahedral state which can be clearly attributed to steric crowding. Such a correlation as (5) confirms the attack at the neighbouring carbonyl group and this intramolecular catalysis for all this series. The activation parameters for the alkaline hydrolysis of these esters were also measured and are shown in Table 1. The enthalpies of activation of the 2-formyl, 2-acetyl, 2-propionyl, 2-isobutyryl and 2-pivaloyl esters are exceptionally small. These are... 

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