Half-sandwich Iridium^IIIN-heterocyclic carbene antitumor complexes and biological applications

Series of half-sandwich Ir^IIIN-heterocyclic carbene (NHC) antitumor complexes [(η⁵-Cp*)Ir(C^C)Cl] have been synthesized and characterized (Cp* is pentamethyl cyclopentadienyl, and C^C are four NHC chelating ligands containing phenyl rings at different positions). Ir^III complexes showed potent antitumor activity with IC₅₀ values ranged from 3.9 to 11.8 μM against A549 cells by the MTT assay. Complexes can catalyze the conversion of the coenzyme NADH to NAD⁺ and induce the production of reactive oxygen species (ROS), and bonding to BSA by static quenching mode. Complexes can arrest the cell cycle in G₁ or S phase and reduce the mitochondrial membrane potential. Confocal microscopy test show complexes could target the lysosome and mitochondria in cells with the Pearson's colocalization coefficient of 0.82 and 0.21 after 12 h, respectively, and followed by an energy-dependent cellular uptake mechanism.