Copper complexes amide hydrolysis

Complexes of metal + ligand + protein or DNA can also catalyze the Diels Alder cycloaddition or oxidations with hydrogen peroxide. Copper complexes bound to DNA catalyzed the Diels-Alder cycloaddition with up to 99% ee [15, 16], Cu(phthalocyanine) complexed to serum albumin also catalyzed the enantioselective (98% ee) Diels-Alder reaction, but only with very high catalyst loading (10 mol%) and only with pyridine-bearing dienophiles (presumably to complex the copper) [17]. Achiral Cr(III) complexes or Mn(Schiff-base) complexes inserted into the active site of apomyoglobin variants catalyzed the sulfoxidation of thio-anisole with up to 13 and 51% ee, respectively [18, 19]. A copper phenanthroline complex attached to the adipocyte lipid-binding protein catalyzed the enantioselective hydrolysis of esters and amides [20]. 

The hydrolysis of coordinated nitriles has recently attracted some attention. A very facile hydrolysis of nitriles to the corresponding amides at platinum(IV) centers has been described.The complex [Cu(H2NCOCH2CONHNH2)Cl] is formed from the reaction NCCH2CONHNH2 the copper(II) both promotes the hydrolysis and is reduced to copper(I). The hydrolysis of 2-cyanopyridine to 2-pyridinecarboxamide is accelerated several hundred times by the copper(II) complexes of the ligands (21) and (22). In the case of the (22) some picolinic acid was formed, resulting from the intramolecular attack of alkoxide to yield an intermediate iminoester. ... 

Rapid amide hydrolysis by copper and zinc complexes of a ligand which mimics the carboxypeptidase active site (7) has been observed. The metal is held perpendicular to the amide plane, and at pH 7.6 and 50 °C hydrolysis occurs 2 X 10 times faster in the presence of zinc than in its absence. Copper is a more potent catalyst. A metal-dependent pliTa ( 8.5 for Zn and 7.6 for Cu +) is consistent with a mechanism in which the amide carbonyl is attacked by a co-ordinated hydroxyl nucleophile. A more sophisticated model with a [20]paracylcophane which has a nucleophilic and a metal binding site attached (8) catalyses the hydrolysis of p-nitrophenyl hexadecanoate. The mechanism... 

Copper(JI) has been found to inhibit the hydrolysis of glycylglycine in basic solution (pH> 11).127 Conley and Martin128 have also found that, at pH values in excess of 11, copper(II) inhibits the hydrolysis of glycinamide due to amide hydrogen ionization. Similar results were obtained with picolinamide, and a bis-picolinamide complex of nickel(II) containing deprotonated amide groups was isolated.128... 

The above studies indicate that metal ions catalyze the hydrolysis of amides and peptides at pH values where the carbonyl-bonded species (25) is present. At higher pH values where deprotonated complexes (26) can be formed the hydrolysis is inhibited. These conclusions have been amply confirmed in subsequent studies involving inert cobalt(III) complexes (Section 61.4.2.2.2). Zinc(II)-promoted amide ionization is uncommon, and the first example of such a reaction was only reported in 1981.103 Zinc(II) does not inhibit the hydrolysis of glycylglycine at high pH, and amide deprotonation does not appear to occur at quite high pH values. Presumably this is one important reason for the widespread occurrence of zinc(Il) in metallopeptidases. Other metal ions such as copper(II) would induce amide deprotonation at relatively low pH values leading to catalytically inactive complexes. 

Three new macrocyclic ligands (187) when complexed with zinc(II) could promote ester hydrolysis and a kinetic study of the hydrolysis of 4-nitrophenyl acetate in Tris buffer at pH 8.63 in 10% (v/v) MeCN was earned out with these.153 The hydrolysis of lipophilic esters is also catalysed by zinc(H) in a complex of a long alkyl-pendant macrocyclic tetraamine (188) in micellar solution.154 A study with a copper chloride-containing micelle has compared its effectiveness in the hydrolysis of esters and amides.155... 

The complex has also been shown to be active in catalysing the hydrolysis of formamide, N-methylformamide and N,N-dimethylformamide in neutral water at 100 C. Monoaqua copper(lI) complexes are not active in catalysing the hydrolysis of the amides under the same conditions [22],... 

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