The hydrolysis of a Co(III) chelated amide catalyzed by an internal phosphonic acid group

In a previous study it was found that an internal carboxylate ion contributed nothing to the rate of hydrolysis of a Co(III) complex of a glycine anilide, although in the enzyme carboxy-peptidase A the catalyzed hydrolysis of peptides is performed by a carboxylate and a Zn2+ ion. However, external acetate ion and even more so external phosphate ion were effective cocatalysts. In the current work we have incorporated a phosphonate ion as an internal cocatalyst for the hydrolysis of a Co(III) complex of a glycine anilide, in two different versions. The internal phosphonate group indeed proves to be effective. The contrast with an ineffective carboxylate ion may in part reflect a different stereoelectronic requirement, but a principal contributor is the increased basicity of the phosphonate group. Its pKa is still not as high as that of the abnormal carboxylate in the enzyme. It is suggested that phosphate or phosphonate groups may be better models than carboxylate ions for the abnormally basic carboxylates found in some enzymes.