Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol

Elesclomol is a novel anticancer agent that has been evaluated in a number of late stage clinical trials. A new and convenient synthesis of elesclomol and its copper complex is described. X-ray crystallographic characterization and the electrochemical properties of the elesclomol copper(II) complex are discussed. The copper(II) cation is coordinated in a highly distorted square-planar geometry to each of the sulphur and amide nitrogen atoms of elesclomol. Electrochemical measurements demonstrate that the complex undergoes a reversible one-electron reduction at biologically accessible potentials. In contrast the free elesclomol is found electrochemically inactive. This evidence is in strong support of the mechanism of action we proposed for the anticancer activity of elesclomol. A new and convenient synthesis of the anticancer agent elesclomol (1) and its copper(II) complex (2) by click chemistry is described. A distinct, highly distorted square planar geometry is shown by 2. Electrochemical measurements demonstrate that the complex 2 undergoes a reversible one-electron reduction at biologically accessible potentials. [Display omitted] •A new and convenient synthesis of the novel anticancer agent elesclomol was developed.•The copper(II) complex of elesclomol was prepared by “click chemistry”.•X-ray crystallographic characterization of the elesclomol copper(II) complex were determined.•A distinct, highly distorted square planar geometry was shown by elesclomol copper(II) complex.