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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Aug 2

PMID 34337263

Authors

Tomiris Nabiyeva

Basile Roufosse

Matylda Odachowski

Judith Baumgartner

Christoph Marschner

Akalesh Kumar Verma

Burgert Blom

Affiliations

Soon will be listed here.

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 σ-germyl, germanate, σ-stannyl, and stannate complexes, along with their cytotoxic (anticancer) investigations. The known dimer complexes [OsCl(η-CH)] () and [OsCl(η--cymene)] () were reacted with PPh to form the known mononuclear complex [OsCl(η--cymene)(PPh)] () and the new complex [OsCl(η-CH)(PPh)] (); complex was reacted with GeCl·(dioxane) and SnCl to afford, by insertion into the Os-Cl bond, the neutral σ-germyl and stannyl complexes [OsCl(η--cymene)(PPh)(GeCl)] () and [OsCl(η--cymene)(PPh)(SnCl)] (), respectively, as a mixture of enantiomers. Similarly, the reaction of complex with GeCl·(dioxane) afforded [OsCl(η-CH)(PPh)(GeCl)] (). Complex , upon reaction with 1,1-bis(diphenylphosphino)methane (dppm), formed a mixture of [OsCl(η--cymene)(κ-dppm)] () and [Os(η--cymene)(κ-dppm)Cl]Cl () when prepared in acetonitrile and a mixture of and the dinuclear complex [[OsCl(η--cymene)](μ-dppm)] () when prepared in dichloromethane. By utilizing either isolated or a mixture of and , the synthesis of κ-dppm germanate and stannate salts, [OsCl(η--cymene)(κ-dppm)]GeCl () and [OsCl(η--cymene)(κ-dppm)]SnCl (), were accomplished halide-abstracting reactions with GeCl·(dioxane) or SnCl, respectively. All resulting complexes were characterized by means of multinuclear NMR, FT-IR, ESI-MS, and UV/Vis spectroscopy. X-ray diffraction analyses of , , , , and 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 and the benzene analogue of complex , , to evaluate the structural changes and the effects on the frontier molecular orbitals arising from the substitution of Ge for Sn. Finally, complexes and - 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 mononuclear 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 molecular interaction simulations and a pharmacokinetic study.

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