Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [(CpRh)-Rh-X((CN)-N-<^>)Z](0/+), in which Cp-X = Cp*, Cp-ph, or Cp-biph, (CN)-N-<^> = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected "piano-stool" configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [(CpRh)-Rh-biph(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD(+) and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [(CpRh)-Rh-biph(benzo[h]quinoline)py](+) (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.