Characterization of Chalkophomycin, a Copper(II) Metallophore with an Unprecedented Molecular Architecture

Abstract

Metals play essential roles in life by coordination with small molecules, proteins, and nucleic acids. Although the coordination of copper ions in many proteins and methanobactins is known, the coordination chemistry of Cu(II) in natural products and their biological functions remain underexplored. Herein, we report the discovery of a Cu(II)-binding natural product, chalkophomycin (CHM, <b>1</b>), from <i>Streptomyces</i> sp. CB00271, featuring an asymmetric square-coordination system of a bidentate diazeniumdiolate and a conjugated 1<i>H</i>-pyrrole 1-oxide-oxazoline. The structure of <b>1</b> may inspire the synthesis of Cu(II) chelators against neurodegenerative diseases or Cu(II)-based antitumor therapeutics.