Activation of oximic nucleophiles by coordination of transition metal ions

A kinetic study of the reactivity in the cleavage of p-nitrophenyl acetate of a series of 2-pyridineoximes, 1-4, and their complexes with Ni(II), Zn(II) and Cu(II) is reported. Complexation of the oximic ligands leads to a remarkable increase in the acidity of the oximic group, following the order Cu(II) > Ni(II) > Zn(II). The oximates of free Ligands and their metal complexes, being alpha-nucleophiles, are quite effective in promoting the cleavage of PNPA. However, the reactivity, as defined by the second-order rate constants, is not predictably related to the acidity of the oximic function. The corresponding Bronsted plot shows a linear behaviour up to a pKa value of ca. 8, above which the reactivity of the uncomplexed oximic functions levels off to a limiting value. In the case of the metal ion complexes, a large effect of the Ligand structure on the reactivity was observed. As a consequence, complexes of appropriate ligands and metal ions show a reactivity that exceeds the apparent limiting one of the oximates. The origin of such effects and their possible implications in the development of new reactivators of phosphorylated acetylcholinesterase are discussed.