Osmium Arene Germyl, Stannyl, Germanate, and Stannate Complexes as Anticancer Agents

T. Nabiyeva, B. Roufosse, M. Odachowski, J. Baumgartner, C. Marschner, A.K. Verma*, B. Blom*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Herein, we describe the synthesis, full spectroscopic characterization, DFT (density functional theory) calculations, and single-crystal X-ray diffraction analyses of a series of osmium arene sigma-germyl, germanate, sigma-stannyl, and stannate complexes, along with their cytotoxic (anticancer) investigations. The known dimer complexes [OsCl2(eta(6)-C6H6)](2) (1) and [OsCl2(eta(6)-p-cymene)](2) (2) were reacted with PPh3 to form the known mononuclear complex [OsCl2(eta(6)-p-cymene)(PPh3)] (3) and the new complex [OsCl2(eta(6)-C6H6)(PPh3)] (6); complex 3 was reacted with GeCl2 center dot(dioxane) and SnCl2 to afford, by insertion into the Os-Cl bond, the neutral sigma-germyl and stannyl complexes [OsCl(eta(6)-p-cymene)(PPh3)(GeCl3)] (7) and [OsCl(eta(6)-p-cymene)(PPh3)(SnCl3)] (11), respectively, as a mixture of enantiomers. Similarly, the reaction of complex 6 with GeCl2 center dot(dioxane) afforded [OsCl(eta(6)-C6H6)(PPh3)(GeCl3)] (9). Complex 2, upon reaction with 1,1-bis(diphenylphosphino)methane (dppm), formed a mixture of [OsCl2(eta(6)-p-cymene)(kappa(1)-dppm)] (4) and [Os(eta(6)-p-cymene)(kappa(2)-dppm)Cl]Cl-+(-) (5) when prepared in acetonitrile and a mixture of 4 and the dinudear complex [[OsCl2(eta(6) -p-cymene)](2) (mu-dppm)] (0) when prepared in dichloromethane. By utilizing either isolated 4 or a mixture of 4 and 5, the synthesis of kappa(2)-dppm germanate and stannate salts, [OsCl(eta(6)-p-cymene)(kappa(2)-dppm)]+GeCl3- (8) and [OsCl(eta(6)-p-cymene)(kappa(2)-dppm)]+SnCl3- (10), were accomplished via halide-abstracting reactions with GeCl2 center dot(dioxane) or SnCl2, respectively. All resulting complexes were characterized by means of multinuclear NMR, FT-IR, ESI-MS, and UV/Vis spectroscopy. X-ray diffraction analyses of 4, 8, 9, 10, and 11 were performed and are reported. DFT studies (B3LYP, basis set LANL2DZ for Os, and def2-TZVPP for Sn, Ge, Cl, P, C, and H) were performed on complex 9 and the benzene analogue of complex 11, 11-benzene, to evaluate the structural changes and the effects on the frontier molecular orbitals arising from the substitution of Ge for Sn. Finally, complexes 3 and 7-11 were investigated for potential anticancer activities considering cell cytotoxicity and apoptosis assays against Dalton's lymphoma (DL) and Ehrlich ascites carcinoma (EAC) malignant cancer cell lines. The complexes were also tested against healthy peripheral blood mononudear cells (PBMCs). All cell lines were also treated with the reference drug cisplatin to draw a comparison with the results obtained from the reported complexes. The study was further corroborated with in silica molecular interaction simulations and a pharmacokinetic study.
Original languageEnglish
Pages (from-to)19252-19268
Number of pages17
JournalAcs omega
Volume6
Issue number29
DOIs
Publication statusPublished - 27 Jul 2021

Keywords

  • ANTITUMOR AGENTS
  • APOPTOSIS
  • BASIS-SETS
  • CANCER-THERAPY
  • DIMETHYL-SULFOXIDE
  • EFFECTIVE CORE POTENTIALS
  • MOLECULAR CALCULATIONS
  • MTT ASSAY
  • RESISTANCE
  • RUTHENIUM

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