Triazole chelators, synthesized by click chemistry, are convenient ligands for palladium(II) and platinum(II). Conformational changes induced by the complexation of these Pd-II and Pt-II complexes with guanosine are similar to those of cisplatin. In addition, these complexes behave like cisplatin with regard to the relaxation of supercoiled plasmid DNA.

Copper(I) -catalysed azide-alkyne cycloaddition (CuAAC) has been successfully conducted under reductant-free conditions. The catalytic system consisted of a combination of a copper(I)-N-heterocyclic carbene complex and aromatic N-donors. The catalyst is stable and can be stored, thus rendering the reaction valuable for routine use.

New weapons to fight cancer are constantly needed. Among chemotherapeutics, anti-cancer metal-drugs have enjoyed a long and successful history since the discovery of the benchmark cisplatin. Advances in metal-drug discovery have motivated chemists to build plethora of complex structures. Among them, a novel area is emerging. This article presents a survey of the metal-N-Heterocyclic Carbenes (Ag(I), Au(I), Pd(II) and Cu(I)-NHCs) as potential anti-cancer agents. Most of the metal-NHCs considered display higher cytotoxicities than the reference metallo-drug cisplatin. Some of them are even selective for particular cell lines. Their mechanisms of action at the cellular level are further discussed, showing that the nature of the metal is of great importance. All these promising results demonstrate that this approach deserves more attention and work.

A simple addition with a large impact: Addition of aromatic amines such as phenanthroline and 4-DMAP (4-dimethylaminopyridine) increases copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) catalytic activity of [CuCl(SIMes)] at a large range of temperatures in such a way that efficient catalysis can safely take place in hydro-alcoholic solvents (see scheme).

Although NHC-complexes are renowned for their catalytic properties, studies of their anti-cancer properties are scarce. In our search for new potent metal-based drugs, we envisioned that copper(I)-NHC could serve as a stable analogue of copper(I)-phenantroline. Herein, we report the results of the biological evaluation of the anticancer properties of [(SIMes)CuCl] 5. This complex showed impressive cytotoxicity against a panel of human tumor cell lines. Regarding IC50, up to 150 fold decrease is observed compared to cisplatin. Cellular effects of [(SIMes)CuCl] were evaluated at the cell cycle and the apoptotic levels. 5 causes cell cycle arrest at the G1 phase as demonstrated by the concomitant accumulation of protein p21 and the strong down-regulation of cyclin D1. Monitoring of poly-(ADP-ribose)-polymerase, implied in apoptosis response of cells, showed that [(SIMes)CuCl] induces apoptosis at low concentration. Finally, we showed that [(SIMes)CuCl] targets DNA by in vitro studies. When inducing aerobic DNA cleavage, [(SIMes)CuCl] behaves analogously to copper(I)-phenantroline. Thus, our experiments evidenced that employing NHC to deliver active copper(I) species in cellulo is a valuable strategy in anticancer research.