Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells
| Autor: | Peter J. Sadler, Russell J. Needham, Hannah E. Bridgewater, Carlos Sanchez-Cano, Paul D. Quinn, Elizabeth M. Bolitho, James P. C. Coverdale |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Denticity Double bond 010405 organic chemistry Ligand chemistry.chemical_element Tripeptide 010402 general chemistry 01 natural sciences Medicinal chemistry 0104 chemical sciences Inorganic Chemistry Metal chemistry visual_art Cancer cell visual_art.visual_art_medium Osmium Chelation |
| Zdroj: | Inorganic Chemistry Frontiers. 8:3675-3685 |
| ISSN: | 2052-1553 |
| DOI: | 10.1039/d1qi00512j |
| Popis: | Transition metal complexes are often prodrugs which undergo activation by ligand exchange and redox reactions before they interact with target sites. It is therefore important to understand the roles of both the metal and the ligands in their activation, especially in cells. Here we use a combination of synchrotron nanoprobe X-ray fluorescence (XRF) from Os L3M5 and Br KL3 emissions and inductively coupled plasma-mass spectrometry (ICP-MS) detection of 189Os, 79Br, and 127I, to investigate the time-dependent accumulation and localization of osmium as well as the monodentate ligand and the chelated phenylazopyridine in A2780 human ovarian cancer cells treated with the potent anticancer complexes [Os(η6-p-cymene)(4-R2-phenyl-azopyridine-5-R1)X]PF6, with R2 = NMe2 or OH, R1 = H or Br, and X = Cl or I. The data confirm that the relatively inert iodido complexes are activated rapidly in cancer cells by release of the iodido ligand, probably initiated by attack by the intracellular tripeptide glutathione (γ-L-Glu-l-Cys-Gly) on the azo double bond. The bond between osmium and the azopyridine appears to remain stable in cells for ca. 24 h, although some release of the chelated ligand is observed. Interestingly, the complexes seem to be degraded more rapidly in normal human cells, perhaps providing a possible mechanism for selective cytotoxicity towards cancer cells. |
| Databáze: | OpenAIRE |
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