Catalysed Hydrolysis Reactions

The first compound described as an artificial enzyme in the literature was the one we reported in which we attached a metal ion binding group to a-cyclodextrin. We found that this would bind p-nitrophenyl acetate into the cavity and a bound nickel ion then catalysed the hydrolysis of the substrate. This was a direct hydrolysis, not an acylation of a cyclodextrin hydroxyl (which is not in reach with the para esters). This type of catalyst then extends metal-catalysed reactions to substrates that do not intrinsically bind to metal ions, which was formerly required for such catalysis. 

Interestingly, in a study of the binding of ditopic substrates to such cyclodextrin dimers we saw that the binding was dominated by an improved enthalpy, rather than entropy. The simplest ideas about chelate binding would have suggested an entropy advantage, but in solution enthalpy-entropy compensation can be seen if the binding or release of water molecules is also considered. 

In a later study we examined the ability of cyclodextrin dimers linked by a bipyridyl unit to catalyse the hydrolysis of a phosphate ester, fcw-p-nitrophenyl phosphate. With a bound lanthanum ion the hydrolysis was accelerated by 300 million-fold, a huge acceleration that could well be of practical interest in the hydrolysis of phosphate esters generally. A full paper described this work in some detail.  

In earlier work we had demonstrated that a zinc complex of pyridyl-2-carboxaldoxime (7) could be effective in cleaving esters. The interesting point is that the oxime anion is available as a nucleophile and the zinc as an electrophile, but they are not coordinated to each other - which would of course destroy the catalytic effect. To amplify catalysis we attached such oxime-zinc complexes to j8-cyclodextrin on both the secondary and primary faces of the cyclodextrin and examined their reaction with p-nitrophenyl acetate. We observed burst kinetics, in which there was an extremely rapid release of one mole of nitrophenoxide ion, followed by a slower release in a second phase. This indicated that we first rapidly produced the acetate of the oxime, and this then slowly hydrolysed to regenerate the oxime anion for further catalytic reaction. Such burst kinetics is very commonly seen in enzymatic reactions of para-nitrophenyl acetate, reflecting the same kind of two-step overall mechanism. 

One problem with such studies is that p-nitrophenyl acetate is a highly reactive ester, and it is more of a challenge to catalyse the hydrolysis of ordinary esters or of amides. In a move in this direction we showed that an appropriate cyclodextrin dimer with a bound copper ion (8) could indeed catalyse the hydrolysis of an ordinary ester group, not a phenyl ester. The acceleration was 18,000-fold, certainly a respectable catalytic result 

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Enzymes that belong to the class of hydrolases are by far the most frequently-applied enzymes in polymer chemistry and are discussed in Chaps. 3-6. Although hydrolases typically catalyse hydrolysis reactions, in synthetic conditions they have also been used as catalysts for the reverse reaction, i.e. the bond-forming reaction. In particular, lipases emerged as stable and versatile catalysts in water-poor media and have been applied to prepare polyesters, polyamides and polycarbonates, all polymers with great potential in a variety of biomedical applications. 

Ab initio calculations have been earned out on the gas-phase acid-catalysed hydrolysis reactions of sulfinamide (319) using the 3-21G sets.290 The first step in the acid-catalysed hydrolysis of A-methylmethanesulfinamide (319 R1 = R2 = Me) is O-protonation and this form is then transformed by addition of water to the sulfiirane intermediate (320). Intramolecular proton transfer from 0 to N follows and then slow N—S bond cleavage to give products.290 Studies with (319 R1 = Me, R2 =aryl) also... 

A fluorescent complex [Ru(r 6-p-cym)Cl(L)]Cl (L = 2-[(2-aminoethyl)amino] ethyl-2-(methylamino)benzoate) has been synthesised by tagging a small fluoro-genic reporter onto the chelating ligand. The interaction of this complex with porcine liver esterase (PLE) showed that esterase-catalysed hydrolysis reactions can liberate methylisatoic acid (MIAH) from the ruthenium complex suggesting a possible use of similar derivatives in esterase-activated Ru-based prodrug delivery systems. The hydrolysis reaction appears to be slow [156]. 

In addition to the application of ABRE in wood chemistry, it has been widely applied to other biomass conversion fields, particularly enzyme catalysed hydrolysis reactions such as the conversion of biopolymers (including cellulose and starch) to monosaccharides and oligosaccharides. In this area, PEG ABS systems offer a benign non-denaturing environment in contrast to organic solvent reaction media. 

Alkyl carbonates are relatively labile concerning the hydrolysis reaction. Surprisingly, polycarbonate polyols give PU that are extremely resistant to hydrolysis, superior to those PU derived from polyesters based on adipic acid and diethylene glycol. The explanation of this paradox, mentioned before, is that between the hydrolysis products of polycarbonate polyols, acidic groups which are able to further catalyse hydrolysis reactions are not formed. The products of polyester polyol hydrolysis are diacids and glycols. The products of polycarbonate polyols hydrolysis are carbon dioxide (a gas which is eliminated easily) and glycols [76] ... 

The acid-catalysed hydrolysis reactions of vinyl epoxides (140 = 1-4) have been shown to follow an A-l mechanism, via the intermediate allylic cations (141). ° The distributions of products from both (140 = 1) and (140 = 3) were similar, comprising all four possible cis- and trans-1,2- and -1,4-diols, whereas cyclohexadiene oxide (140 = 2) gave mainly the trans-... 

The reaction (1) shows that fluorine severely catalyses hydrolysis reaction [3]. In the hydrolysis reaction, because of the smaller ionic radius of the fluorine, which approaches a molecule of TEOS in the solution forming a highly unstable pentacovalent activated intermediate. This complex rapidly decomposes, forming a partially fluorinated and hydroxylated silicon alkoxide. 

Base-catalysed hydrolysis reaction of an aUcoxide proceeds much slower than acid-catalysed hydrolysis. Once hydrolysis has taken place, the reaction proceeds gradually. It is also nucleophilic SN-2 type of reaction. 

There are many types of enzyme-catalysed hydrolysis reactions. In this chapter, the hydrolysis of esters and amides will be surveyed quite extensively, while the hydrolysis of nitriles and epoxides will be mentioned briefly at the end. The use of hydrolase enzymes in organic solvents will be discussed also, in connection with the preparation of esters and amides. 

By considering both non-catalysed and self-catalysed hydrolysis reactions, the chain cleavage rate can be expressed according to Pan (Han et al., 2010 Wang et al., 2008) as ... 

Hydrolysis reaction, non-catalysed hydrolysis reaction and auto-catalysed reaction. 

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