Novel iridium(III) iminopyridine complexes: synthetic, catalytic, and in vitro anticancer activity studies

Organometallic half-sandwich Ir^III complexes of the type [(η⁵-Cp^x)Ir(N^N)Cl]PF₆ 1-6, where Cp^x = C₅Me₅ (Cp*), C₅Me₄C₆H₅ (Cp^xph), C₅Me₄C₆H₄C₆H₅ (Cp^xbiph), N^N is imionopyridine chelating ligand, were prepared and characterized. The X-ray crystal structure of complex 1 has been determined. Four compounds displayed higher anticancer potency than clinically used anticancer drug cisplatin against A549 cancer cells, especially complex 3 which is 8 times more active than cisplatin. No hydrolysis was observed by NMR and UV-Vis for complexes 3 and 6; however, these complexes show big differences in nucleobase binding, mainly decided by the imionopyridine chelating ligand. Complex 3 is stable in the presence of glutathione, but 6 reacted rapidly with glutathione. The octanol/water partition coefficients (log P) of 3 and 6 have been determined. In addition, these complexes display effective catalytic activity in converting coenzyme NADH to NAD⁺ by accepting hydride to form an Ir hydride adduct. The mechanism of actions of these complexes involves apoptosis induction, cell cycles arrest, and significant increase of reactive oxygen species levels in A549 cancer cells.