Potent Half-Sandwich Iridium(III) and Ruthenium(II) Anticancer Complexes Containing a P^O-Chelated Ligand

Abstract

We herein report the synthesis, characterization, and anticancer activity of a series of iridium(III) and ruthenium(II) half-sandwich complexes of the type [(Cpx/arene)M(P^O)Cl]PF6 (M = Ir, Cpx = pentamethylcyclopentadienyl (Cp*) or its phenyl (Cpxph = C5Me4C6H5) or biphenyl (Cpxbiph = C5Me4C6H4C6H5) derivatives; M = Ru, arene = p-cymene (p-cym); P^O = phosphine phosphonic amide ligand (PPOA)). The X-ray crystal structures of all complexes, in which the ligand can form six-membered rings with the metal center, have been determined. All of the complexes show remarkable anticancer activities toward HeLa and A549 cancer cells, activities which are higher than that of the clinical anticancer drug cisplatin. The incorporation of phenyl substituents on the Cp* ring for iridium(III) complexes results in little variation in their anticancer activities. These results can be attributed to the combinatorial action of the metal and PPOA ligand. Hydrolysis and DNA cleavage are not the major mechanisms of action. These...