Inactivation of thiostrepton by copper(II)

Summary Among the various bivalent metal ions tested, only copper(II) was found to bind to thiostrepton (M_rr 1650) in a stoichiometric ratio of 4:1. The binding of four copper ions to a thiostrepton molecule resulted in (a) irreversible loss in biological activity and (b) a change in the ultraviolet absorption spectrum of the antibiotic. Potentiometric titration of thiostrepton in the presence of copper(II) revealed dissociation of the antibiotic with a loss of 11 protons/molecule. Based on the preferential ability of copper(II) to bind to thiostrepton in the presence of some copper-complexing compounds containing similar ligand groups to the antibiotic, the possible co-ordinating atoms of the thiostrepton molecule involved in binding to the metal ion are discussed.