Mitochondrial targeting half-sandwich iridium(III) and ruthenium(II) dppf complexes and in vitro anticancer assay

Abstract

Considering the potential application of half-sandwich and ferrocenyl-containing organometallic complexes in the area of anticancer, four half-sandwich iridium(III) (Ir^III) and ruthenium(II) (Ru^II) diphenylphosphino ferrocene (dppf) complexes were prepared in this study. Complexes showed favorable anti-proliferation activity towards A549 cell lines compared to cisplatin, meanwhile, which could effectively inhibit cell migration. These complexes followed an energy dependence uptake mechanism, effectively accumulated in mitochondria with a Pearson's Colocalization Coefficient (PCC) of 0.77, decreased the mitochondrial membrane potential, induced a surge of reactive oxygen species, disturbed cell cycle, and eventually led to apoptosis. Western blot assay further confirmed that these complexes induced apoptosis following a mitochondrial pathway. Above all, half-sandwich Ir^III and Ru^II dppf complexes show the prospect of becoming a new multifunctional therapeutic platform for mitochondrial targeted imaging and anticancer drugs.

Keywords: Anticancer; Dppf; Half-sandwich structure; Iridium(III) complex; Mitochondrial pathway; Ruthenium(II) complex.