Anticancer Iron–Iridium Organometallic Conjugates

The diiron vinyliminium complexes [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(3-C5H4N)CHCN(R)(Me)}]CF3SO3 (Cp
= η5-C5H5; R = 2,6-C6H3Me2 = Xyl, 2a, R = Me, 2b) reacted with [IrCp*(Phpy)Cl] (IrCl; Cp* = η5-C5Me5, Phpy = κN,κC-2-phenylpyridine) and
AgCF3SO3 to afford the bis-cationic iron–iridium
conjugates [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(3-C5H4NIrCp*Phpy)CHCN(Me)(R)}][CF3SO3]2 (4a–b), in nearly quantitative yields. Similarly, the reaction
of the ferracyclic compound [FeCp(CO){CN(Me)(Xyl)CHC(3-C5H4N)C(O)}] (3a) with [IrCp*(Phpy)Cl]/AgNO3 led to the monocationic species [FeCp(CO){CN(Me)(Xyl)CHC(3-C5H4NIrCp*Phpy)C((O)}]NO3 (5a, 70% yield). The new complexes 4a–b and 5a were characterized by mass spectrometry,
IR and 1H and 13C NMR spectroscopy. NMR and
DFT analyses indicate that they exist as pairs of diastereoisomers
due to the chirality centers in the iron and iridium scaffolds, and
that the coordination strength of the pyridyl ligand to iridium is
comparable to that observed in the iridium-pyridine adduct [IrCp*(py)(Phpy)]
(Irpy). The cytotoxicity of 4a–b and 5a was evaluated on cancer (A2780, A549,
U87) and noncancerous (MRC-5) cell lines, with 5a exhibiting
superior activity compared to cisplatin and Irpy, along
with a tendency toward selectivity. The activity of 4a–b and 5a, which is significantly
higher compared to their iron precursors, is associated with enhanced
iridium uptake in cancer cells (aligning with lipophilicity, determined
as Log Pow values), suppression of oxygen
consumption rate and elevated ROS production.