Cobalt complexes ester hydrolysis

In a different approach three different structurally defined aza-crown ethers were treated with 10 different metal salts in a spatially addressable format in a 96-well microtiter plate, producing 40 catalysts, which were tested in the hydrolysis of /xnitrophenol esters.32 A plate reader was used to assess catalyst activity. A cobalt complex turned out to be the best catalyst. Higher diversity is potentially possible, but this would require an efficient synthetic strategy. This research was extended to include lanthanide-based catalysts in the hydrolysis of phospho-esters of DNA.33... 

Metal-ion catalysis has been extensively reviewed (Martell, 1968 Bender, 1971). It appears that metal ions will not affect ester hydrolysis reactions unless there is a second co-ordination site in the molecule in addition to the carbonyl group. Hence, hydrolysis of the usual types of esters is not catadysed by metal ions, but hydrolysis of amino-acid esters is subject to catalysis, presumably by polarization of the carbonyl group (KroU, 1952). Cobalt (II), copper (II), and manganese (II) ions promote hydrolysis of glycine ethyl ester at pH 7-3-7-9 and 25°, conditions under which it is otherwise quite stable (Kroll, 1952). The rate constants have maximum values when the ratio of metal ion to ester concentration is unity. Consequently, the most active species is a 1 1 complex. The rate constant increases with the ability of the metal ion to complex with 2unines. The scheme of equation (30) was postulated. The rate of hydrolysis of glycine ethyl... 

It has been known for many years that the rate of hydrolysis of a-amino acid esters is enhanced by a variety of metal ions such as copper(II), nickel(II), magnesium(H), manganese(II), cobalt(II) and zinc(II).338 Early studies showed that glycine ester hydrolysis can be promoted by a tridentate copper(II) complex coupled by coordination of the amino group and hydrolysis by external hydroxide ion (Scheme 88).339 Also, bis(salicylaldehyde)copper(II) promotes terminal hydrolysis of the tripeptide glycylglycylglycine (equation 73).340 In this case the iV-terminal dipeptide fragment... 

Many more recent stoichiometric studies of cobalt(III) complexes have been responsible for most of the developments in this area of research. Cobalt(III) ammine complexes effect hydrolysis of ethyl glycinate in basic conditions via intramolecular attack of a coordinated amide ion hydrolysis by external hydroxide ion attack also occurs (equation 74).341 Replacement of ammonia ligands by a quadridentate or two bidentate ligands allows the formation of aquo-hydroxo complexes and enables intramolecular hydroxide ion attack on a coordinated amino ester, amino amide... 

Owing to the snccess of cobalt(III)-mediated hydrolysis of amino acid esters, the next step was to examine how these complexes reacted with peptides. If similar hydrolytic results could be obtained with peptides, then one of the potential uses of cobalt(III) complexes would be in the N-terminal determination and seqnential analysis of polypeptides. This area has been investigated by several gronps. Peptides... 

Even though this dipeptide is turned over quite slowly, the complex examined is probably a non-productive one. Furthermore an analogous ester substrate has not been found, and it is known that carboxypeptidase behaves quite differently toward ester and peptide substrates. In particular, the kinetic parameters for peptide hydrolysis for a series of metal substituted carboxypeptidases indicate that fccat values can range from 6000 min for the cobalt enzyme down to 43 min for the cadmium enzyme 66). The values on the other hand are almost totally independent of the particular metal present. The exact opposite is true for ester hydrolysis. Km varies from 3300 M for the cobalt enzyme to 120 M for the cadmium enzyme while k<.at is essentially unchanged. 

Another way of bringing reactants into close proximity, which is encountered commonly in transition metal chemistry, is through metal ion complexation. The coordination of a reactant to a metal ion complex often activates its reactivity and can bring the reactant into close proximity with a second reactant or with a catalytic group. One example, shown in Fig. 6, is a zinc (11) complex of 1,5,9-triazacyclononane, as a model for the enzyme carbonic anhydrase, which contains a zinc (11) cofactor in its active site (4). In the aqua complex, the bound water molecule has a dramatically reduced pKa value of 7.3, which is similar to the pKa of the active site nucleophihc water. The corresponding cobalt (111) complex catalyzed ester hydrolysis at twice the rate because Co(lll) can coordinate both the hydroxide nucleophile and the ester carbonyl via a... 

Co(in) complexes promote similar reactions. When four of the six octahedral positions are occupied by amine ligands and two cis positions are available for further reactions, it is possible to study not only the hydrolysis itself, but the steric preferences of the complexes. In general, these compounds catalyze the hydrolysis of N-terminal amino acids from peptides, and the amino acid that is removed remains as part of the complex. The reactions apparently proceed by coordination of the free amine to cobalt, followed either by coordination of the carbonyl to cobalt and subsequent reaction with OH or H2O from the solution (path A in Figure 12-15) or reaction of the carbonyl carbon with coordinated hydroxide (path B). As a result, the N-terminal amino acid is removed from the peptide and left as part of the cobalt complex in which the a-amino nitrogen and the carbonyl oxygen are bonded to the cobalt. Esters and amides are also hydrolyzed by the same mechanism, with the relative importance of the two pathways dependent on the specific compoimds used. 

Two different binuclear copperdi) complexes have been prepared recently, one with a bridging phenoxy ligand having two bis-benzi-midazole arms (12, Fig. 14), and the second having a bis-cyclen-naphthalene ligand (13, Fig. 15) (352, 353). Both of them show bimetallic cooperativity for the hydrolysis of phosphate diesters, contrary to studies with the dinuclear cobalt complex (354). The pseudo-first-order rate constants for hydrolysis of the para-nitrophenylphosphate ester of propylene glycol by bis-benzimidazole-based copper complexes... 

The cobalt(III)-promoted hydrolysis of amino acid esters and peptides and the application of cobalt(III) complexes to the synthesis of small peptides has been reviewed. The ability of a metal ion to cooperate with various inter- and intramolecular acids and bases and promote amide hydrolysis has been investigated. The cobalt complexes (5-10) were prepared as potential substrates for amide hydrolysis. Phenolic and carboxylic functional groups were placed within the vicinity of cobalt(III) chelated amides, to provide models for zinc-containing peptidases such as carboxypeplidase A. The incorporation of a phenol group as in (5) and (6) enhanced the rate of base hydrolysis of the amide function by a factor of 10 -fold above that due to the metal alone. Intramolecular catalysis by the carboxyl group in the complexes (5) and (8) was not observed. The results are interpreted in terms of a bifunctional mechanism for tetrahedral intermediate breakdown by phenol. 

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