Contrasting Biological Behavior of Deep Red Luminescent Ru(II) and Ir(III) Complexes Bearing Phosphonium Pendants

Abstract

Four luminescent complexes based upon heteroleptic complex formulas [Ru(bipy)2(L)]n+ or [Ir(tmq)2(L)]n+ (where bipy = 2,2′-bipyridine; tmq = 2,6,7-trimethyl-3-phenylquinoxaline) are reported. These complexes are functionalized via an ancillary 2-(2-pyridinyl)-4-quinolinecarboxamide ligand to incorporate either a pendant alcohol group (LOH) or a triphenylphosphonium cation (LTPP). All complexes were characterized using a range of spectroscopic and analytical techniques: multinuclear NMR, IR, UV–vis and luminescence spectroscopies, HRMS, and cyclic voltammetry. Photophysical studies describe the red phosphorescent nature of the complexes and show that the Ru(II) species are longer wavelength emitters (λem = 719 and 724 nm) compared to the Ir(III) species (λem = 641 and 643 nm); the Ru(II) complexes are weaker emitters in aerated solvent (ϕ < 0.1%) compared to the Ir(III) species (ϕ = 3.5 and 3.9%). A range of biological studies were conducted on the complexes: antiproliferative activity, cyto- and photocytotoxicity assays, quantification of cell uptake, cell cycle and reactive oxygen species assays, cell imaging using confocal fluorescence microscopy and wound healing assays. The Ir(III) complexes reveal markedly enhanced antiproliferative and light-activated activity compared to the Ru(II) analogues, primarily driven by higher cellular uptake and efficient intracellular accumulation. Quantitative colocalization analysis confirmed enhanced mitochondrial targeting for [Ir(tmq)2(LTPP)]2+.