Acetals hydrolysis, metal catalysis

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

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). 

Przystas and Fife427 have studied the hydrolysis of substituted benzaldehyde methyl 8-quinolyl acetals such as (135) in 50% dioxane-water at 30 °C. These acetals are subject to both general and specific acid catalysis. A variety of divalent metal ions (Cu11, Co11, Ni11, Mn11 and Zn11) exert... 

Catalyst 17 is effective only with substrates that can bind to the metal ion, so we attached it - coordinated as its Ni2+ derivative - to the secondary face of a-cyclodextrin in catalyst 21 [102]. This was then able to use the metallo-oxime catalysis of our previous study, but with substrates that are not metal ligands, simply those that bind hy-drophobically into the cyclodextrin cavity. As hoped, we saw a significant rate increase in the hydrolysis of p-nitrophenyl acetate, well beyond that for hydrolysis without the catalyst or for simple acetyl transfer to the cyclodextrin itself. Since there was full catalytic turnover, we called compound 21 an artificial enzyme - apparently the first use of this term in the literature. The mechanism is related to that proposed earlier for the enzyme alkaline phosphatase [103]. 

The most numerous cases of homogeneous catalysis are by certain ions or metal coordination compounds in aqueous solution and in biochemistry, where enzymes function catalytically. Many ionic effects are known. The hydronium ion H3O and the hydroxyl ion OH catalyze hydrolyses such as those of esters ferrous ion catalyzes the decomposition of hydrogen peroxide decomposition of nitramide is catalyzed by acetate ion. Other instances are inversion of sucrose by HCl, halogenation of acetone by H and OH , hydration of isobutene by acids, hydrolysis of esters by acids, and others. 

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. 

---