Activation by Oxidation: Ferrocene-Functionalized Ru(II)-Arene Complexes with Anticancer, Antibacterial, and Antioxidant Properties
| Autor: | John R. Thompson, Changhua Mu, Rikesh Panchmatia, Soumalya Sinha, Shane Harrypersad, Gregory A. MacNeil, Jeffrey J. Warren, Kathleen E. Prosser, Charles J. Walsby |
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| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Metallocenes Antineoplastic Agents Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Medicinal chemistry Antioxidants Ruthenium Inorganic Chemistry chemistry.chemical_compound Picrates Pyridine Organometallic Compounds Humans Imidazole Molecule Ferrous Compounds Physical and Theoretical Chemistry Bimetallic strip Cell Proliferation Molecular Structure 010405 organic chemistry Biphenyl Compounds Anti-Bacterial Agents 0104 chemical sciences Ferrocene chemistry Piperidine Drug Screening Assays Antitumor Cyclic voltammetry Antibacterial activity HT29 Cells Oxidation-Reduction Bacillus subtilis |
| Zdroj: | Inorganic Chemistry. 57:15247-15261 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/acs.inorgchem.8b02542 |
| Popis: | Organometallic Ru(II)-cymene complexes linked to ferrocene (Fc) via nitrogen heterocycles have been synthesized and studied as cytotoxic agents. These compounds are analogues of Ru(II)-arene piano-stool anticancer complexes such as RAPTA-C. The Ru center was coordinated by pyridine, imidazole, and piperidine with 0-, 1-, or 2-carbon bridges to Fc to give six bimetallic, dinuclear compounds, and the properties of these complexes were compared with their non-Fc-functionalized parent compounds. Crystal structures for five of the compounds, their Ru-cymene parent compounds, and an unusual trinuclear compound were determined. Cyclic voltammetry was used to determine the formal MIII/II potentials of each metal center of the Ru-cymene-Fc complexes, with distinct one-electron waves observed in each case. The Fc-functionalized complexes were found to exhibit good cytotoxicity against HT29 human colon adenocarcinoma cells, whereas the parent compounds were inactive. Similarly, antibacterial activity from the Ru-cymene-Fc compounds was observed against Bacillus subtilis, but not from the unfunctionalized complexes. In both cases, the IC50 values correlated quantitatively with the Fc+/0 reduction potentials. This is consistent with more facile oxidation to give ferrocenium, and subsequent generation of toxic reactive oxygen species, leading to greater cytotoxicity. The antioxidant properties of the complexes were quantified by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. EC50 values indicate that linking of the Ru and Fc centers promotes antioxidant activity. |
| Databáze: | OpenAIRE |
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