title: Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity.
abstract: A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(μ-ox)(NO)}4](5-) (Ln=Y, Dy). While Y(III) is eight-coordinate in 2, Dy(III) is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 μM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Währinger Strasse 42, 1090 Vienna (Austria).
authors.forename: Paul-Steffen
authors.initials: PS
authors.lastname: Kuhn
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Währinger Strasse 42, 1090 Vienna (Austria).
authors.forename: Laura
authors.initials: L
authors.lastname: Cremer
authors.affiliation: Université Claude Bernard Lyon 1, Laboratoire des Multimatériaux et Interfaces (UMR 5615), Campus de la Doua, 69622 Villeurbanne cedex (France).
authors.forename: Anatolie
authors.initials: A
authors.lastname: Gavriluta
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia).
authors.forename: Katarina K
authors.initials: KK
authors.lastname: Jovanović
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia).
authors.forename: Lana
authors.initials: L
authors.lastname: Filipović
authors.affiliation: Universität Wien, Fakultät für Chemie, Institut für Biophysikalische Chemie, Althanstraße 14, 1090 Wien (Austria).
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Hummer
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Währinger Strasse 42, 1090 Vienna (Austria).|Present address: Division for Physical Sciences and Engineering and KAUST Catalysis Center, King Abdullah University of Science and Technology, Thuwal (Saudi Arabia).
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Büchel
authors.affiliation: University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Center of Chemistry, Studentski trg 12-16, Belgrade (Serbia).
authors.forename: Biljana P
authors.initials: BP
authors.lastname: Dojčinović
authors.affiliation: Faculty of Chemistry, Institute of Analytical Chemistry, University of Vienna, Währinger Strasse 38, 1090 Vienna (Austria).
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Meier
authors.affiliation: Universität Wien, Fakultät für Chemie, Institut für Biophysikalische Chemie, Althanstraße 14, 1090 Wien (Austria).
authors.forename: Annette
authors.initials: A
authors.lastname: Rompel
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia).
authors.forename: Siniša
authors.initials: S
authors.lastname: Radulović
authors.affiliation: Université Claude Bernard Lyon 1, Laboratoire des Multimatériaux et Interfaces (UMR 5615), Campus de la Doua, 69622 Villeurbanne cedex (France).
authors.forename: Jean Bernard
authors.initials: JB
authors.lastname: Tommasino
authors.affiliation: Université Claude Bernard Lyon 1, Laboratoire des Multimatériaux et Interfaces (UMR 5615), Campus de la Doua, 69622 Villeurbanne cedex (France). dominique.luneau@univ-lyon1.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Luneau
authors.affiliation: University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, Währinger Strasse 42, 1090 Vienna (Austria). vladimir.arion@univie.ac.at.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D009589:Nitrogen Oxides; D012428:Ruthenium
keywords: antitumor agents; lanthanide; nitrosyl; osmium; ruthenium