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

Abstract

Herein, we present the synthesis of new complexes based on ruthenium(II) (Ru(η⁶-p-cymene)Cl₂PPh₂CH₂OH (RuPOH) and Ru(η⁶-p-cymene)Cl₂P(p-OCH₃Ph)₂CH₂OH (RuMPOH)) and iridium(III) (Ir(η⁵-Cp*)Cl₂P(p-OCH₃Ph)₂CH₂OH (IrMPOH) and Ir(η⁵-Cp*)Cl₂PPh₂CH₂OH (IrPOH)) containing phosphine ligands with/without methoxy motifs on phenyl rings (P(p-OCH₃Ph)₂CH₂OH (MPOH) and PPh₂CH₂OH (POH)). The complexes were characterized by mass spectrometry, NMR spectroscopy (1D: ¹H, ¹³C{¹H}, and ³¹P{¹H} 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 η⁶-coordinated arene (Ru^II complexes) or η⁵-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)₂CH₂OH (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: av. 48.3 μM; after 72 h: av. 10.2 μM) while Ir(III) complexes were found to be moderate against prostate cancer cells (DU145).