Novel heteronuclear IrIII-CuII coordination compounds ([Ir(η5-Cp*)Cl2Pcfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (1), [Ir(η5-Cp*)Cl2Pnfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (2), [Ir(η5-Cp*)Cl2Plfx-Cu(phen)](NO3)·1.3(H2O)·1.95(CH3OH) (3), [Ir(η5-Cp*)Cl2Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of IrIII in all complexes adopts a characteristic piano-stool geometry with the η5-coordinated and three additional sites occupied by two chloride and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around CuII ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(η5-Cp*)Cl2Plfx-Cu(phen)] features the one-dimensional (1D) metal-organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(η5-Cp*)Cl2Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated.

Department of Chemical Engineering and Environmental Technologies University of Zaragoza Campus Río Ebro Edificio 1 D Mariano Esquillor S N 50018 Zaragoza Spain

Department of Chemical Pharmaceutical and Agricultural Sciences University of Ferrara Via L Borsari 46 44121 Ferrara Italy

Department of Inorganic Chemistry Faculty of Science Palacky University 17 listopadu 12 CZ 771 46 Olomouc Czech Republic

Faculty of Chemistry Jagiellonian University Gronostajowa 2 30 387 Kraków Poland

Faculty of Chemistry University of Wroclaw Joliot Curie 14 50 383 Wroclaw Poland

Faculty of Chemistry Wroclaw University of Science and Technology Wybrzeże Wyspiańskiego 27 50 370 Wroclaw Poland

Instituto de Nanociencia y Materiales de Aragón CSIC Universidad de Zaragoza 50009 Zaragoza Spain

Małopolska Centre of Biotechnology Jagiellonian University Gronostajowa 7A 30 387 Krakow Poland

Networking Research Center on Bioengineering Biomaterials and Nanomedicine CIBER BBN 28 029 Madrid Spain

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