Half-sandwich iridium(III) complexes with α-picolinic acid frameworks and antitumor applications

Eight half-sandwich iridium(III) (Ir-III) complexes of the general formula [(eta(5)-Cp-xbiPh)Ir(O boolean AND N)Cl] (Cp-xbiPh is tetramethyl(biphenyl)cyclopentadienyl, and the O boolean AND N is alpha-picolinic acid chelating ligand and its derivatives) were synthesized and characterized. Compared with cis-platin widely used in clinic, target Ir-III complexes showed at most five times more potent antitumor activity against A549 cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Ir-III complexes could be transported by serum albumin, bind with DNA, catalyze the oxidation of nicotinamide-adenine dinucleotid (NADH) and induce the production of reactive oxygen species, which confirmed the antitumor mechanism of oxidation. Ir-III complexes could enter A549 cells followed by an energy-dependent cellular uptake mechanism, meanwhile, target the mitochondria and lysosomes with the Pearson's colocalization coefficient of 0.33 and 0.74, respectively, lead to the lysosomal destruction and the change of mitochondrial membrane potential (Delta psi m), and eventually induce apoptosis.