Cu2+ PROMOTED HYDROLYSIS REACTIONS OF SIDE CHAIN FUNCTIONAL GROUPS. MODELS FOR HYDROLYTIC METALLO ENZYMES

Using three examples it is shown how the metal ion incorporated i n the macrocyclic ring modifies the reactivity of functional groups i n the side chain. The first series includes Cu2+ promoted hydrolysis reactions of a nitrile 2 , of several esters 3-5, of a phosphonate ester 6 and of an amide 7. The mechanism of the hydrolysis of the nitrile and of the phosphonate ester are consistent with an internal O H attack onto the functional group, whereas that of the carboxylic ester hydrolysis cannot defenitively be proven. The second example consists i n the selective acylation of only one amino group of the bis-functionalized macrocycle 8, which has two equivalent side chains. Since the metal ion coordinates only one of them., it is possible to selectively benzoylate the other one. The third example shows how monoN-functionalized macrocyclic metal complexes of 1 1 can be coupled to amines and proteins. This allows to prepare isotopically marked antibodies, which have diagnostic and therapeutic applications i n nuclear medicine.