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

We report the synthesis, characterisation and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp^XRh(C^N)Z]^0/+, in which Cp^X = Cp*, Cp^ph, or Cp^biph, C^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 hydrolysed faster in aqueous solution, also reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5,-tetramethylcyclopentadienyl complex [Cp^biphRh(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 [Cp^biphRh(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.