2-Aryl-1 H -imidazo[4,5- f ][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents.

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [ Ru ₂ L1 , Ru ₂ L2 , Ir ₂ L1 , Ir ₂ L2 , Re ₂ L1 , and Re ₂ L2 ] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru ₂ L1 and Ir ₂ L2 are two proficient complexes among all, but Ru ₂ L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕ _f ) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru ₂ L1 -treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir ₂ L2 -treated cells, which correlated with autophagy reticence.