Heteropentanuclear Oxalato‐Bridged nd–4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis,Crystal Structures,Aqueous Stability and Antiproliferative Activity |
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| Authors: | Dr Paul‐Steffen Kuhn B Sc Laura Cremer Dr Anatolie Gavriluta Dr Katarina K Jovanović Dr Lana Filipović Dr Alfred A Hummer Dr Gabriel E Büchel Dr Biljana P Dojčinović Dr Samuel M Meier Prof Dr Annette Rompel Dr Siniša Radulović Dr Jean Bernard Tommasino Dr Dominique Luneau Prof Dr Vladimir B Arion |
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| Institution: | 1. University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, W?hringer Strasse 42, 1090 Vienna (Austria);2. Université Claude Bernard Lyon 1, Laboratoire des Multimatériaux et Interfaces (UMR 5615), Campus de la Doua, 69622 Villeurbanne cedex (France);3. Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia);4. Universit?t Wien, Fakult?t für Chemie, Institut für Biophysikalische Chemie, Althanstra?e 14, 1090 Wien (Austria);5. Present address: Division for Physical Sciences and Engineering and KAUST Catalysis Center, King Abdullah University of Science and Technology, Thuwal (Saudi Arabia);6. University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Center of Chemistry, Studentski trg 12‐16, Belgrade (Serbia);7. Faculty of Chemistry, Institute of Analytical Chemistry, University of Vienna, W?hringer Strasse 38, 1090 Vienna (Austria) |
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| Abstract: | A series of heteropentanuclear oxalate‐bridged Ru(NO)‐Ln (4d–4f) metal complexes of the general formula (nBu4N)5Ln{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)2RuCl3(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 13C NMR spectroscopy. X‐ray diffraction showed that in 2 and 5 four complex anions RuCl3(ox)(NO)]2? are coordinated to YIII and DyIII, respectively, with formation of Ln{RuCl3(μ‐ox)(NO)}4]5? (Ln=Y, Dy). While YIII is eight‐coordinate in 2 , DyIII 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)5Ln{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. |
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| Keywords: | antitumor agents lanthanide nitrosyl osmium ruthenium |
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