Homo‐ and heterodinuclear arene‐linked osmium(II) and ruthenium(II) organometallics: probing the impact of metal variation on reactivity and biological activity

Wilson, Christopher S.; Prior, Timothy J.; Sandland, Jordon; Savoie, Huguette; Boyle, Ross W.; Murray, Benjamin S.

Abstract

Dinuclear metallodrugs offer much potential in the development of novel anticancer chemotherapeutics as a result of the distinct interactions possible with biomacromolecular targets and the unique biological activity that can result. Here, we describe the development of isostructural homodinuclear Os(II)‐Os(II) and heterodinuclear Os(II)‐Ru(II) organometallic complexes formed from the linking of the arene ligands of [M(η6‐arene)(C2O4)(PTA)] (M = Os/Ru; PTA = 1,3,5‐triaza‐7‐phosphaadamantane) units. Together with the known Ru(II)‐Ru(II) analogue, a chromatin‐modifying agent, we probed the impact of variation of the metal ions on the structure, reactivity and biological activity of these complexes. The complexes have been structurally characterised by X‐ray diffraction experiments, their stability and reactivity examined using 1H and 31P NMR spectroscopy and biological activity assessed, alongside mononuclear analogues, through MTT assays and cell cycle analysis (HT‐29 cell line). Results revealed high antiproliferative activity in each case with cell cycle profiles of the dinuclear complexes found to be similar to that for untreated cells, and similar but distinct profiles for the mononuclear complexes. These results indicate these complexes impact on cell viability predominantly through a non‐DNA damaging mechanism of action. The new Os(II)‐Os(II and Os(II)‐Ru(II) complexes reported here are further examples of a family of compounds operating via mechanism(s) of action atypical of the majority of metallodrugs, and which have potential as tools in chromatin research.

Citation

Wilson, C. S., Prior, T. J., Sandland, J., Savoie, H., Boyle, R. W., & Murray, B. S. (in press). Homo‐ and heterodinuclear arene‐linked osmium(II) and ruthenium(II) organometallics: probing the impact of metal variation on reactivity and biological activity. Chemistry: a European journal, https://doi.org/10.1002/chem.202002052

• Journal Article Type: Article
• Acceptance Date: Jun 9, 2020
• Online Publication Date: Jun 10, 2020
• Deposit Date: Jul 21, 2020
• Publicly Available Date: Jun 11, 2021
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1002/chem.202002052
• Keywords: Bioorganometallic; Metallodrugs; Bioinorganic; Cancer; Dinuclear complexes
• Public URL: https://hull-repository.worktribe.com/output/3546414
• Publisher URL: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202002052
• Additional Information: Received: 2020-04-27; Accepted: 2020-06-09; Published: 2020-06-10