Methylation as an effective way to generate SOD-activity in copper complexes of scorpiand-like azamacrocyclic receptors☆

Abstract Methylation of the secondary amine groups of a scorpiand-type ligand consisting of a pyridine spacer connected through methylene groups to a tris(2-aminomethyl) unit with the pendant arm further functionalised with a 3-pyridine unit leads to a ligand whose Cu(II) complex exhibits threefold enhanced SOD activity with respect to the non-methylated ligand. Potentiometric studies indicate the formation of [CuL] 2+ species with a stability three orders of magnitude lower than that formed with the related non-methylated ligand. Kinetic studies indicate that methylation of the secondary nitrogens causes a deceleration of both the complex formation and the acid-induced dissociation of the metal ion. The reduction in stability associated to the poorer σ-donor ability of the tertiary amino groups shifts the Cu(II)/Cu(I) redox potentials towards more positive values permitting a better cycling between both states needed for the dismutation of superoxide radicals.