Catalysis of hydrolysis

Hydrolysis of coordinated ligands is a special case of nucleophilic attack. Two examples involving inorganic ligands have already been given in Section II. A on aquation of cobalt(III) complexes. Many further examples will be found in the following Section VII.B on catalysis of hydrolysis of organic substrates by metal ions and complexes. 

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

Catalysis of hydrolysis of P-lactams by dinuclear zinc complexes... 

In this section, however, the stereoselective catalysis of hydrolysis will be described more fully in relation to the stereoselective nature of the enzyme reaction. According to Bunton et al. (1971b), (R)- and (S)-p-nitrophenyl O-methylmandelates [35] were hydrolyzed at an identical rate in borate buffers in the presence of CTAB, while a (R/S) mixture was hydrolyzed at a rate greater than either the (/ )- or (S)-enantiomer alone. They also reported that... 

At this point, we can integrate much of what has been discussed above in a single case study. Antibody NPN43C9 was reported in 1988 as the first example of catalysis of hydrolysis of an amide bond, in fact of an active anilide. Its structure and mode of action have been well studied (Janda et al., 1988b), which makes it an appropriate example for this purpose. 

R. Mendez, T. Alemany, J. Martin-Villacorta, Catalysis of Hydrolysis and Aminolysis of Non-Classical /3-Lactam Antibiotics by Metal Ions and Metal Chelates , Chem. Pharm. Bull. 1992, 40, 3228-3233. 

J. Martin, R. Mendez, F. Salto, Studies on Clavulanic Acid. Part 2. Catalysis of Hydrolysis and Aminolysis of Clavulanic Acid by Metal Chelates , J. Chem. Soc., Perkin Trans. 2, 1990, 43-46. 

Table IV. Metal Ion Catalysis of Hydrolysis of Esters Containing Free...

The nucleophilic reactions of acetyl phosphate are catalyzed by cations such as magnesium (26), calcium (15, 32), and even lithium (30). Most of the reactions involve catalysis of hydrolysis. Calcium ion catalyzes a neutral as well as a... 

Catalysis of hydrolysis is observed if the reaction with the nucleophile is faster than hydrolysis under the reaction conditions, as long as the initial product is also more reactive than the starting material, viz. 

If the anhydride derived from R"COOH is more reactive than the original anhydride, catalysis of hydrolysis is observed. If it is less reactive, hydrolysis is inhibited. The first case amounts to nucleophilic catalysis of hydrolysis. 

If the anhydride formed is more reactive than the ester, as is generally the case, nucleophilic catalysis of hydrolysis should result. There is ample evidence supporting this mechanism. 

These principles appear to hold for nucleophilic catalysis of hydrolysis by other species also. The evidence for catalysis by amino-compounds is discussed below. Catalysis by a wide variety of oxyanions (and other anions) has been measured by several authors, particularly of the hydrolysis of p-nitrophenyl acetate. This is a convenient substrate kinetically, since the release of / -nitrophenoxide is easily followed spectrophotometrically at 400 nm, but perhaps not ideal mechanistically, since, as described above, at least some of its reactions involve a mixture of mechanisms. A selection of data, obtained under the same conditions in one laboratory283, is given in Tables 37 and 38. Some of these data are plotted logarithmically (in Fig. 17) against the... 

Fig. 17. Bronsted plot for the reactions of nucleophiles with p-nitrophenyl acetate in water at 25°C. These reactions involve simple nucleophilic catalysis of hydrolysis. (Data from ref. 283).

Fig. 18. Bronsted plot for the reactions of nucleophiles with phenyl acetate (PA,D)p-nitrophenyl acetate (PNPA, A) and 2,4-dinitrophenylacetate (DNPA,0) at 25°C. The open symbols (and full lines) represent data for the total reaction, which is in most cases nucleophilic catalysis. The closed symbols (and broken lines) represent general base catalysis of hydrolysis.

The experimental evidence that these reactions do, in fact, represent general base catalysis, rather than nucleophilic catalysis of hydrolysis, is very strong. The solvent deuterium isotope effect of 2-3 (Table 39) is consistent with the breaking of a bond to hydrogen in the rate-determining step of the reaction ... 

The reaction of an amine with an ester generally produces an amide, and catalysis of hydrolysis occurs only in two special situations. Tertiary amines cannot give amides, and may act as nucleophiles or general bases to catalyze ester hydrolysis, and general base catalysis of hydrolysis may be observed with any amine, as long as competing reactions (in particular aminolysis) are relatively slow. 

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. 

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