Mitochondrial targeted rhodium(III) complexes: Synthesis, characterized and antitumor mechanism investigation

Recently, rhodium complexes have received intensive attentions due to their tunable chemical and biological properties as well as attractive antitumor activity. In this work, two imidazole triphenylamino rhodium complexes [Rh(ppy)2L1]PF6 (Rh1) and [Rh(ppy)2L2]PF6 (Rh2) (ppy = 2-phenylpyridine, L1 = 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline, L2 = N-(4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl)-4-methyl-N-(p-tolyl)aniline) have been synthesized and characterized. Both complexes display stronger anticancer activity against a various of cancer cells than cisplatin and they can effectively localize to mitochondria. Further mechanism studies show that Rh1 induce caspase-dependent apoptosis through mitochondrial damage, down-regulate the expression of B-cell lymphoma-2 (Bcl-2)/Bcl2-associated x (Bax) and reactive oxygen species (ROS) elevation. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of rhodium complexes. Imidazole-based triphenylamino (TPA) rhodium(III) complex could target the mitochondria in cells, increased the levels of reactive oxygen species (ROS) and the decrease of mitochondrial membrane potential (MMP), and eventually leading to caspase-dependent death pathway. [Display omitted] •Two new Rh(III) complexes were synthesized and characterized.•The designed Rh(III) complexes exhibit higher cytotoxicity to cancer cells than cisplatin.•Rh(III) complexes specifically localize to mitochondrial.•Rh(III) complexes induce apoptosis-related events mediated by mitochondria.