Synthesis, physicochemical characterization and antiproliferative activity of phosphino Ru(II) and Ir(III) complexes

Herein, we present the synthesis of new complexes based on ruthenium(II) (Ru(eta(6)-p-cymene) Cl2PPh2CH2OH (RuPOH) and Ru(eta(6)-p-cymene)Cl2P(p-OCH3Ph)(2)CH2OH (RuMPOH)) and iridium(III) Ir(eta(5)-Cp*)Cl2P(p-OCH3Ph)(2)CH2OH (IrMPOH) and Ir(eta(5)-Cp*)Cl2PPh2CH2OH (IrPOH)) containing phosphine ligands with/without methoxy motifs on phenyl rings (P(p-OCH3Ph)(2)CH2OH (MPOH) and PPh2CH2OH (POH)). The complexes were characterized by mass spectrometry, NMR spectroscopy (1D: H-1, C-13{H-1), and P-31{H-1) and 2D: HMQC, HMBC, and COSY NMR) and elemental analysis. All the complexes were structurally identified by single-crystal X-ray diffraction analysis. The Ru(II) and Ir(III) complexes have a typical piano-stool geometry with an eta(6)-coordinated arene (Ru-II complexes) or eta(5)-coordinated (Ir-III compounds) and three additional sites of ligation occupied by two chloride ligands and the phosphine ligand. Oxidation of NADH to NAD(+) with high efficiency was catalyzed by complexes containing P(p-OCH3Ph)(2)CH2OH (IrMPOH and RuMPOH). The catalytic property might have important future applications in biological and medical fields like production of reactive oxygen species (ROS). Furthermore, the redox activity of the complexes was confirmed by cyclic voltamperometry. Biochemical assays demonstrated the ability of Ir(III) and Ru(II) complexes to induce significant cytotoxicity in various cancer cell lines. Furthermore, we found that RuPOH and RuMPOH selectively inhibit the proliferation of skin cancer cells (WM266-4; IC50, after 24 h: ay. 48.3 mu M; after 72 h: av. 10.2 mu M) while Ir(m) complexes were found to be moderate against prostate cancer cells (DU145).

Automated summary

In this study, new complexes based on ruthenium(II) and iridium(III) with phosphine ligands and phenyl rings with/without methoxy motifs were synthesized and characterized. The complexes showed high catalytic efficiency in the oxidation of NADH to NAD(+) and exhibited potential applications in biological and medical fields. Furthermore, they demonstrated redox activity and significant cytotoxicity against various cancer cell lines.