Fluorescent half-sandwich phosphine-sulfonate iridium(III) and ruthenium (II) complexes as potential lysosome-targeted anticancer agents

The synthesis, characterization and biological activity of neutral fluorescent Ir(III) and Run half-sandwich organometallic complexes containing phosphine-sulfonate ligands are reported. X-ray crystal structure of complexes 1-3, 10 and 11 exhibits the expected half-sandwich three-legged piano-stool pseudo-octahedral geometry. Spectroscopic properties study displays that these complexes show rich fluorescence properties. With the exception of 9, 10 and 11 toward A549 human lung cancer cells and 10 towards HeLa human cervical cancer cells, each complex shows promising cytotoxicity toward HeLa and A549 cells line with IC50 values in the range of 3.6-53.1 mu M, and 6.5-34.5 mu M, respectively. Hydrolysis, DNA cleavage and depolarization of the mitochondrial membrane potential (MMP) appear not to be the main mechanism of action. However, these complexes are able to covert NADH to NAD via the transfer hydrogenation. Mechanism studies by flow cytometry display that the complexes exert their anticancer efficacy by inducing apoptosis, perturbing the cell cycle and increasing the intracellular ROS level. Furthermore, fluorescence property of these complexes provides a tool to investigate the microscopic mechanism by confocal microscopy. Notably, the typical Ir(III) complex 3 can specially localize to lysosome and damage it. In addition, complex 3 enters into HeLa cells mainly through energy-dependent pathway.