Zinc catalysis hydrolysis

R. Breslow, D. E. McClure, R. S. Brown, and J. Eisenach (1975), Very fast zinc catalyzed hydrolysis of an anhydride. A model for the rate and mechanism of carboxypeptidase A catalysis. /. Amer. Chem. Soc. 97,194-195. 

Cheng, S., Zeng, X., Meng, X., Yu, X. MetaUomiceUar catalysis hydrolysis of p-nitrophenyl pieolinate catalyzed by copper(II), nickel(II), and zinc(II) complexes of long alkylpyridine ligands in micellar solution. 7. Colloid Interface Sci. 2000, 224(2), 333-337. 

Carboxypeptidases are zinc-containing enzymes that catalyze the hydrolysis of polypeptides at the C-terminal peptide bond. The bovine enzyme form A is a monomeric protein comprising 307 amino acid residues. The structure was determined in the laboratory of William Lipscomb, Harvard University, in 1970 and later refined to 1.5 A resolution. Biochemical and x-ray studies have shown that the zinc atom is essential for catalysis by binding to the carbonyl oxygen of the substrate. This binding weakens the C =0 bond by... 

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... 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

Zinc-dependent enzymes [EC 3.5.2.6], including penicillinase and cephalosporinase, with varying specificity in their catalysis of j8-lactam hydrolysis. Some act more readily on penicillins, whereas the catalysis of others is more efficient with cephalosporins. 

This type of alkoxylation chemistry cannot be performed with conventional alkali metal hydroxide catalysts because the hydroxide will saponify the triglyceride ester groups under typical alkoxylation reaction conditions. Similar competitive hydrolysis occurs with alternative catalysts such as triflic acid or other Brpnsted acid/base catalysis. Efficient alkoxylation in the absence of significant side reactions requires a coordination catalyst such as the DMC catalyst zinc hexacyano-cobaltate. DMC catalysts have been under development for years [147-150], but have recently begun to gain more commercial implementation. The use of the DMC catalyst in combination with castor oil as an initiator has led to at least two lines of commercial products for the flexible foam market. Lupranol Balance 50 (BASF) and Multranol R-3524 and R-3525 (Bayer) are used for flexible slabstock foams and are produced by the direct alkoxylation of castor oil. 

The copper(II)-promoted hydrolysis of glycylglycine has been studied in some detail.120 Copper(II) ions catalyze the hydrolysis of glycylglycine in the pH range 3.5 to 6 at 85 °C.120 The pH rate profile has a maximum at pH 4.2, consistent with the view that the catalytically active species in the reaction is the carbonyl-bonded complex. The decrease in rate at higher pH is associated with the formation of a catalytically inactive complex produced by ionization of the peptide hydrogen atom. This view has subsequently been confirmed by other workers,121 in conjunction with an IR investigation of the structures of the copper(II) and zinc(II) complexes in D20 solution.122 Catalysis by cobalt(II),123 and zinc(II), nickel(II) and manganese(II) has also been studied.124-126... 

Very significant zinc(II) catalysis has been observed in the hydrolysis of 2-pyridylphosphonosul fate (71).266 A possible structure for the intermediate or transition state for this reaction is showr in (72). 

Breslow and coworkers420 have studied the hydrolysis of the anhydrides (128) and (129) in both the presence and absence of zinc(II) (and other metal ions). In the the absence of metal ion, hydrolysis of the anhydrides is independent of pH in the region 1.0-7.5, as also occurs with phthalic anhydride.421 However, in the presence of zinc(II), the hydrolysis is first order in hydroxide above pH 5. Table 28 lists values of kobs for the various substrates at pH 7.5 (for the metal complex k0bs = kOH[0H-]). The catalytic effects are of the order of 103. The pH dependence of the zinc(II) catalysis is consistent with attack by external hydroxide on a complex such as (130) where the metal acts as a Lewis acid catalyst. A further possibility involves attack by coordinated hydroxide on an uncoordinated anhydride carbonyl (131), and there is some evidence that this is indeed the process which does occur. 

Thus, many metal ions catalyze the hydrolysis of esters [7,8], amides [9], and nitriles [10] via electrophilic activation of the C=0 or C=N group. This type of catalysis is characteristic of coordination complexes and is very common in metalloenzyme-mediated processes. Zinc(II), for example, is a key structural component of more than 300 enzymes, in which its primary function is to act as a Lewis acid (see Chapter 4). The mechanism of action of zinc proteases, e.g., thermolysin, involves electrophilic activation of an amide carbonyl group by coordination to zinc(II) in the active site (Figure 4). 

Artificial enzymes with metal ions can also hydrolyze phosphate esters (alkaline phosphatase is such a natural zinc enzyme). We examined the hydrolysis of p-nitro-phenyfdiphenylphosphate (29) by zinc complex 30, and also saw that in a micelle the related complex 31 was an even more effective catalyst [118]. Again the most likely mechanism is the bifunctional Zn-OH acting as both a Lewis acid and a hydroxide nucleophile, as in many zinc enzymes. By attaching the zinc complex 30 to one or two cyclodextrins, we saw even better catalysis with these full enzyme mimics [119]. A catalyst based on 25 - in which a bound La3+ cooperates with H202, not water - accelerates the cleavage of bis-p-nitrophenyl phosphate by over 108-fold relative to uncatalyzed hydrolysis [120]. This is an enormous acceleration. 

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