Understanding the modes of action of β-ketoiminato iridium(III) complexes in cancer cells

Stringer, Tameryn, Yildirim, Büşra, Sergi, Baris, Hofmann, Benjamin J., Lee, Yi-Hsuan, Acilan, Ceyda and Lord, Rianne M. (2025) Understanding the modes of action of β-ketoiminato iridium(III) complexes in cancer cells. Inorganic Chemistry, 64 (34). pp. 17189-17199. ISSN 0020-1669

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Abstract

Four new charged iridium(III) 1,2,3,4,5-pentamethylcyclopentadienyl (Cp*) complexes, 1–4, of the type [Cp*Ir(L1–4)(PTA)](PF6) (where L1–4 = functionalized β-ketoiminate ligands and PTA = 1,3,5-triaza-7-phosphaadamantane), have been successfully synthesized and characterized. Single crystal X-ray crystallographic data have been obtained for all compounds and confirm a typical pseudo-octahedral half-sandwich geometry. Cytotoxicity values have been determined against a range of cancerous and noncancerous cell lines and highlight high cytotoxicity and selectivity toward breast cancers. Among these compounds, the unfunctionalized β-ketoiminate Ir(III) complex (1) emerged as the most promising candidate, demonstrating activity that was comparable to or exceeded that of cisplatin, especially after 24 h against the triple-negative MDA-MB-231 cell line. Morphological and molecular analyses confirmed that 1 triggers apoptotic cell death, involving caspase activation and PARP cleavage, which is consistent with its DNA-damaging characteristics, highlighting the future anticancer potential of compound 1.

Item Type:	Article
Additional Information:	Acknowledgments: The authors would like to thank Orfhlaith McCullough at the London Metropolitan University for elemental analysis and the UKRI Future Leader Fellow scheme [MR/T041315/1] for funding of B.J.H., Y.H.L. and R.M.L. The authors also express their sincere appreciation for the services and facilities provided by the Koç University Research Center for Translational Medicine (KUTTAM).
Uncontrolled Keywords:	physical and theoretical chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1606
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology Faculty of Science > School of Chemistry (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Chemistry of Materials and Catalysis Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	17 Nov 2025 15:30
Last Modified:	17 Nov 2025 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101034
DOI:	10.1021/acs.inorgchem.5c02026

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