REACTIONS OF VANADIUM(V) COMPLEXES OF N,N-DIMETHYLHYDROXYLAMINE WITH SULFUR-CONTAINING LIGANDS - IMPLICATIONS FOR PROTEIN-TYROSINE-PHOSPHATASE INHIBITION

The equilibrium reactions in aqueous solution of the vanadate complex bis(N,N-dimethylhydroxamido)hydroxooxovanadate with dithiothreitol, cy steine and several related compounds have been studied. The highly fav oured products form rapidly with displacement of a single dimethylhydr oxylamine ligand to form a vanadium-dimethylhydroxylamine-ancillary li gand complex of 1:1:1 stoichiometry. The reaction is promoted by the t hiol group and requires one additional functional group. Such addition al groups include hydroxyl, amino, carboxyl and amido functionalities. The long-term stability of the starting complex compared to the rapid formation of products is interpreted in terms of an associative mecha nism for the reaction. The relevance of these findings to the potent i nhibition of protein tyrosine phophatases by the bis(dimethylhydroxami do)vanadate complex is discussed.