Exploiting Natural Products to Build Metalla-Assemblies: The Anticancer Activity of Embelin-Derived Rh(III) and Ir(III) Metalla-Rectangles

Six new pentamethylcyclopentadienyl Rh(III) and Ir(III) metalla-rectangles ([3](CF(3)SO(3))(4)–[8](CF(3)SO(3))(4)) have been prepared by a self-assembly strategy using the embelin-derived metalla-clips (η(5)-C(5)Me(5))(2)M(2)(μ(4)-C(6)HRO(4)-κO)Cl(2) (M = Rh, 1; M = Ir, 2; R = (CH(2))(10)CH(3)) and the linear ditopic ligands, pyrazine, 4,4'-bipyridine and 1,2-bis(4-pyridyl)ethylene. These new metalla-rectangles have been obtained in high yield and isolated as their triflate salts. The complexes have been fully characterized by standard spectroscopic techniques and the antiproliferative activity of these tetranuclear complexes was evaluated in vitro on cancerous (DU-145, A-549, HeLa) and noncancerous (HEK-293) cell lines. The biological study has showed a better activity for the rhodium derivatives over the iridium analogs and for all complexes a very good selectivity for cancerous over noncancerous cells. The presence of lipophilic side chains coupled with the positive charge of the tetranuclear complexes suggested a cytotoxic activity involving the mitochondrial machinery, as demonstrated by multiple biological experiments.