Piano stool Ru(II)-arene complexes having three monodentate legs: A comprehensive review on their development as anticancer therapeutics over the past decade

The popularity of RAPTA-C in in vivo studies has steered the way for complexes of the type [Ru(eta(6)-arene) (X)(Y)(Z)](n+) (where X, Y and Z are monodentate ligands) to be developed for biological, primarily, anticancer applications. This has led them to become a class of their own, with extensive research in this area happening over the past decade. The choice of three monodentate ligands plus the arene in the piano stool skeleton of these complexes allows the researchers to control and tweak their chemical properties dexterously. These complexes are tuned to inhibit various enzyme functions or selectively target specific cancer cell lines by integrating appropriate ligands into the system. Ligands with biological relevance synergistically enhance the overall activity, which has been the key basis for constructing such complex systems. The activation mechanism of these bifunctional complexes involves the hydrolysis of the Ru-X bond (X is mostly halido ligand), which can be fine-tuned by choosing an appropriate primary ligand. These complexes adopt a multitargeted approach in binding to biomolecules and generally have been reported to promote cell death via apoptosis. This review mainly focuses on the structural and molecular alterations in the design and development of Ru(II)-arene complexes with monodentate (cheifly P, N or S) ligand(s) for anticancer applications, and their behaviour in in vitro or in vivo.CO 2022 Elsevier B.V. All rights reserved.