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

Research output: Contribution to journalArticlepeer-review

Authors

  • Elizabeth M. Bolitho
  • Hannah E. Bridgewater
  • Russell J. Needham
  • Paul D. Quinn
  • Carlos Sanchez-Cano
  • Peter J. Sadler

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)3675-3685
Number of pages11
JournalInorganic Chemistry Frontiers
Volume8
Issue number15
Early online date10 Jun 2021
Publication statusPublished - 7 Aug 2021

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