Copper(ii) binding by kanamycin A and hydrogen peroxide activation by resulting complexes

Abstract

Protonation and copper(II) coordination properties of kanamycin A were studied in solution by potentiometry, UV-Vis, circular dichroism (CD), EPR and cyclic voltammetry (CV). Only mononuclear complexes of stoichiometries ranging from CuH₂L to CuH₋₂L were found. Kanamycin A anchors Cu(II) ions with an {NH₂, O⁻} chelate of the C-ring of its molecule. At pH higher than 6 the amino and hydroxyl groups of the A-ring of kanamycin A also participate in binding. The resulting structure, similar to that of complexes of other unsubstituted aminoglycosides studied previously, involves Cu(II) coordination by donors of terminal aminosugar rings, rather than those of the central unit. The results of cyclic voltammetry investigations, kinetic studies of H₂O₂ disproportionation and ROS detection experiments, further supported the mechanism of oxidative reactivity of cupric complexes of aminoglycosides, proposed by us recently [M. Jeżowska-Bojczuk, W. Leśniak, W. Bal, H. Kozłowski, K. Gatner, A. Jezierski, J. Sobczak, S. Mangani and W. Meyer-Klaucke; Chem. Res. Toxicol., 2001, 14, 1353–1362], which involves Cu(I) and Cu(III) redox states and both metal-bound and free ROS.