Copper Complexes of N‐Donor Ligands as Artificial Nucleases

Abstract

This microreview summarizes recent research in the field of artificial nucleases, in particular those based on copper(II) in an N‐donating ligand environment. This review is divided into three parts describing different ligand classes that have shown promising results in DNA cleavage chemistry: aromatic N‐donors, aliphatic N‐donors, and peptide ligands. Whereas nature has created very efficient nucleases, artificial nucleases aim at different selectivities and higher stability under various conditions. Artificial nucleases based on metal complexes comprise Lewis acidic or redox‐active metal centers allowing for either hydrolytic or oxidative DNA cleavage. The focus of our research and thus also of this microreview is copper, whose CuII ion combines both properties. Depending on the ligand scaffold and reaction conditions, either pathway or even both are thus conceivable. Those different pathways lead to molecular biological and medicinal applications.

Copper–Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity

“…96,97 In most cases, copper–oxygen intermediates have not been identified as distinct intermediates in ROS generation, but data in support of the “intermediacy of a ROS that is intimately bound to the copper center” 98 has been presented for copper bound to the amino terminal Cu(II)- and Ni(II)-binding (ATCUN) peptide motif. 99–101 The nature of such “intimately bound” ROS/copper species is not known.…”

Transition Metal Complexes with 1‐Adamantoyl Hydrazones – Cytotoxic Copper(II) Complexes of Tri‐ and Tetradentate Pyridine Chelators Containing an Adamantane Ring System

“…Most copper(II) complexes exert antitumor effects by damaging the double-stranded DNA molecules through covalent interactions or intermolecular associations, which include groove binding, electrostatic interactions, and intercalation. [7,8] Very recently, some copper(II) complexes with acylhydrazone ligands were reported as efficient DNA binders with enhanced cytotoxic potency, and correlation between DNA binding and cytotoxic activity is often an important step in the investigation of new antitumor agents. The square-pyramidal and square-planar Cu II complexes derived from bis(benzoylhydrazone) showed superior DNA binding properties, [9] whereas Cu II complexes with ferrocene-based acylhydrazones exhibited significant cleavage of supercoiled pUC19 DNA in the presence of hydrogen peroxide as co-oxidant.…”

DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex

“…Cytotoxic Cu(II) complexes often show DNA cleavage activity [4,7,8], suggesting a connection between these two properties. The mechanism of Cu complex-induced DNA strand breaks often involves the formation of reactive oxygen species (ROS) through the Fenton reaction following the reduction of Cu(II) to Cu(I) by biological reducing agents such as ascorbic acid.…”