Peptide hydrolysis copper complexes

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... 

E. L. Hegg, J. N. Burstyn, Hydrolysis of Unactivated Peptide Bonds by a Macrocyclic Copper(II) Complex Cu([9]aneN3)Cl2 Hydrolyzes Both Dipeptides and Proteins , J. Am. Chem. Soc. 1995, 117, 7015-7016. 

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. 

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