Half-sandwich Ru(II) N-heterocyclic carbene complexes in anticancer drug design

The ruthenium arene fragment is a rich source for the design of anticancer drugs; in this design, the co-ligand is a critical factor for obtaining effective anticancer complexes. In comparison with other types of ligands, N-heterocyclic carbenes (NHCs) have been less explored, despite the versatility in structural modifications and the marked stabilization of metal ions, being these characteristics important for the design of metal drugs. However, notable advances have been made in the development of NHC Ruthenium arene as anticancer agents. These advances include high antitumor activities, proven both in in vitro and in in vivo models and, in some cases, with marked selectivity against tumorigenic cells. The versatility of the structure has played a fundamental role, since they have allowed a selective interaction with their molecular targets through, for example, bio-conjugation with known anticancer molecules. For this reason, the structure-activity relationship of the imidazole, benzimidazole, and abnormal NHC ruthenium (II) η⁶-arene complexes have been studied. Taking into account this study, several synthetic aspects are provided to contribute to the next generations of this kind of complexes. Moreover, in recent years nanotechnology has provided innovative nanomedicines, where half-sandwich Ruthenium(II) complexes are paving their way. In this review, the recent developments in nanomaterials functionalized with Ruthenium complexes for targeted drug delivery to tumors will also be highlighted.