Issue 15, 2021

Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells

Abstract

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.

Graphical abstract: Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells

Supplementary files

Article information

Article type
Research Article
Submitted
18 apr 2021
Accepted
27 may 2021
First published
10 iyn 2021
This article is Open Access
Creative Commons BY license

Inorg. Chem. Front., 2021,8, 3675-3685

Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells

E. M. Bolitho, H. E. Bridgewater, R. J. Needham, J. P. C. Coverdale, P. D. Quinn, C. Sanchez-Cano and P. J. Sadler, Inorg. Chem. Front., 2021, 8, 3675 DOI: 10.1039/D1QI00512J

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