Ligand-controlled reactivity and cytotoxicity of cyclometalated rhodium(III) complexes

We report the synthesis, characterisation and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp(X)Rh(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(biph)Rh(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(biph)Rh(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.