Mechanism of hydrolysis

FIGURE 27 19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A The peptide is bound at the active site by an ionic bond between its C terminal ammo acid and the positively charged side chain of arginine 145 Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water... 

Hydrolysis studies compared a polycarbonate urethane with a poly(tetramethyl-ene adipate) urethane and a polyether urethane based on PTMEG. After 2 weeks in 80°C water, the polycarbonate urethane had the best retention of tensile properties [92], Polycarbonates can hydrolyze, although the mechanism of hydrolysis is not acid-catalyzed, as in the case of the polyesters. Polycarbonate polyurethanes have better hydrolysis resistance than do standard adipate polyurethanes, by virtue of the highest retention of tensile properties. It is interesting to note in the study that the PTMEG-based urethanes, renowned for excellent hydrolysis resistance, had lower retention of physical properties than did the polycarbonate urethanes. 

The mechanisms of all the reactions cited in Table 20.1 are similar to the mechanism of hydrolysis of an acyl chlor ide outlined in Figure 20.2. They differ with respect to the nucleophile that attacks the carbonyl group. 

The mechanism of hydrolysis and alcoholysis has been described, and the greater reactivity of the 4-position over the 2-position is attributed to the greater stability of the transition complex (20) with respect to (21), hence its greater ease of formation. The hydrolysis... 

The kinetic and thermodynamic properties of Fischer-type carbene complexes have also been addressed by Bernasconi, who relates the strength of the 7r-donor substituent to the thermodynamic acidity [95-101] and the kinetics and mechanism of hydrolysis and reversible cyclization to differences in the ligand X [96,102]. 

For a discussion of the mechanism of hydrolysis of alkyl nitrites, see Williams, D.L.H. Nitrosation Cambridge University Press Cambridge, 1988, p. 162. 

A. Phosphoenolpyruvate.—The mechanisms of hydrolysis of phosphate esters of phosphoenol pyruvic acid (33) have been described in detail, and 0 studies confirm an earlier postulate that attack by water on the cyclic acyl phosphate (34) occurs at phosphorus and not at carbon. In the enolase reaction, the reversible interconversion of 2-phosphoglyceric acid(35)... 

The results confirm that RG-hydrolase is a true rhamnogalacturonase, as it splits an alternating RG chain, and furthermore that it cleaves between GalA and Rha in the main chain by a mechanism of hydrolysis (Schols et al., 1990a). Similarly, the products from the RGO s with higher DP s were characterised. 

The lack of glycosyl transfer reaction is the class of pectinolytic hydrolases is in agreement with the observed inversion of the anomeric configuration of the newly formed reducing ends of the products. All three polygalacturonases studied here utilize the single displacement mechanism of hydrolysis. 

A viscometric assay and identification of hydrolysis products were used to determine the mechanism of action of PG. An endo-PG is characterized by a strong reduction in viscosity (e.g. 50%) with a concomitantly low (e.g. 1-3%) release of reducing groups [9]. The time required for 50% decrease in viscosity of a 3.0% (w/v) sodium polypectate solution at 25°C was approximately 10 min, at which time about 1.5% of the total galacturonide bonds had been hydrolysed (data not shown). These results reveal a random mechanism of hydrolysis of sodium polypectate and the enzyme was a poly oc(l,4)-D-galacturonide glycanohydrolase (EC 3.2.1.15) or endo-PG. 

There has been controversy over the mechanism of hydrolysis of ethylene methyl phosphate and investigations into the nature of metaphosphate and its role in the hydrolysis of phosphorus esters have continued. Elegant experiments relating to each of these problems have been reported. 

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. 

The mechanism of hydrolysis of o-carboxyaryl phosphates, whose dianions also hydrolyze much faster then, e.g., the phenyl phosphate monoanion 79,80) (maximum rate at about pH 4.8 and 25 °C 81)), was long a point of mechanistic contention. Thorough investigations81 led to proposal of a fast initial transprotonation... 

Mechanisms for nucleophilic aliphatic substitution at glycosides, 41, 277 Mechanisms of hydrolysis and rearrangements of epoxides, 40, 247 Mechanisms of oxygenations in zeolites, 42, 225 Mechanisms, nitrosation, 19, 381... 

Ring opening reactions are the main feature of a brief review (though with 69 references) of kinetics and mechanisms of hydrolysis and substitution reactions of platinum(II) complexes (219). 

Fig. 3 Zanamivir , an antiviral drug which inhibits viral sialidases and below the mechanism of hydrolysis of sialosides with the transition state 4 mimed by Zanamivir .

The mechanism of hydrolysis of benzylidenetriphenylphosphorane is similar to that of the corresponding phosphonium salt.52 It is proposed that the low polarities of the solutions in which ylides are usually hydrolysed increase the equilibrium... 

Peptide hydrolases (peptidases or proteases, i.e., enzymes hydrolyzing peptide bonds in peptides and proteins, see Chapt. 2) have received particular attention among hydrolases. As already described in Chapt. 2, peptidases are divided into exopeptidases (EC 3.4.11 -19), which cleave one or a few amino acids from the N- or C-terminus, and endopeptidas-es (proteinases, EC 3.4.21-99), which act internally in polypeptide chains [2], The presentation of enzymatic mechanisms of hydrolysis in the following sections will begin with peptidases and continue with other hydrolases such as esterases. 

The mechanism of hydrolysis of cysteine peptidases, in particular cysteine endopeptidases (EC 3.4.22), shows similarities and differences with that of serine peptidases [2] [3a] [55 - 59]. Cysteine peptidases also form a covalent, ac-ylated intermediate, but here the attacking nucleophile is the SH group of a cysteine residue, or, rather, the deprotonated thiolate group. Like in serine hydrolases, the imidazole ring of a histidine residue activates the nucleophile, but there is a major difference, since here proton abstraction does not appear to be concerted with nucleophilic substitution but with formation of the stable thiolate-imidazolium ion pair. Presumably as a result of this specific activation of the nucleophile, a H-bond acceptor group like Glu or Asp as found in serine hydrolases is seldom present to complete a catalytic triad. For this reason, cysteine endopeptidases are considered to possess a catalytic dyad (i.e., Cys-S plus H-His+). The active site also contains an oxyanion hole where the terminal NH2 group of a glutamine residue plays a major role. 

The antihypertensive agent tripamide (4.267), when incubated with rat liver microsomes or partially purified microsomal arylamidase, was extensively hydrolyzed to 4-chloro-3-sulfamoylbenzoic acid (4.268) [171]. This metabolite seems to be produced by direct hydrolysis, since the other metabolites formed by oxidation of the cycloalkyl moiety remained unchanged when incubated with rat liver microsomes. The mechanism of hydrolysis of tripamide has not yet been fully elucidated. The inhibition of the reaction by O-ethyl 0-(4-nitro-phenyl) phenyl phosphothionate indicates that amidases may be involved. 

Fig. 5.6. Different mechanisms of hydrolysis of the (S-lactam bond, namely a) base-catalysis, b) acid-catalysis, and c) general base catalysis by H20...

Such a restriction does not exist for a readily accessible experimental parameter such as the chemical shift of the carbonyl C-atom (A<5). This parameter, as measured by 13C-NMR, expresses a complex mixture of electronic and steric effects, some of which may not be relevant to the mechanism of hydrolysis. Its correlation with log k is not as good as that of Taft s polarity parameter, yet it is of sufficient quality and includes enough variation between substituents to have fair predictive value (Eqn. 8.2) ... 

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