Redox-Active Organoruthenium(II)- and Organoosmium(II)-Copper(II) Complexes, with an Amidrazone-Morpholine Hybrid and [Cu^ICl₂]^- as Counteranion and Their Antiproliferative Activity

A novel proligand HL^H has been prepared from 2-pyridinamidrazone and 6-(morpholinomethyl)pyridine-2-carboxaldehyde. Subsequently, starting from HL^H and CuCl₂·2H₂O in the presence of triethylamine, a series of homo- and heterometallic complexes with [Cu^ICl₂]^- as counteranion, namely mononuclear complex [Cu^IICl(HL^OMe)][Cu^ICl₂] (1), dinuclear Ru(II)-Cu(II) complex [Cu^IIRu^II(η⁶-p-cymene)Cl₂(L^H)][Cu^ICl₂]·1.5H₂O (2·1.5H₂O), Os(II)-Cu(II) complex [Cu^IIOs^II(η⁶-p-cymene)Cl₂(L^H)][Cu^ICl₂]·H₂O (3·H₂O), and tetranuclear complex [Cu^II₄(L¹)₂(L²)₂Cl₂]·5MeOH (4·5MeOH), where HL^OMe, L¹, and L² are Schiff base ligands derived from HL^H, were synthesized. The structures of metal complexes were established by X-ray diffraction. Complexes 1-3 demonstrated quasireversible one-electron reduction of Cu(II) in complex cations and one-electron oxidation of [Cu^ICl₂]^- counterion, confirmed by UV-vis and EPR spectroelectrochemical measurements. They exhibited moderate antiproliferative activity against ovarian carcinoma and cervical adenocarcinoma cell lines in a micromolar concentration range, which was superior to the activity of HL^H, CuCl₂, and [Cu^ICl₂]^-. The observed anticancer effects might be related to the ability of novel complexes to generate ROS, which was established by spin trapping experiments in cell-free media as well as by confocal microscopic imaging in ovarian carcinoma cells.