Photoactivated Osmium Arene Anticancer Complexes

Xuling Xue, Ying Fu, Liang He, Luca Salassa, Ling-Feng He, Yuan-Yuan Hao, Madeleine J. Koh, Clément Soulié, Russell J. Needham, Abraha Habtemariam, Claudio Garino, Kirill A. Lomachenko, Zhi Su, Yong Qian, Martin J. Paterson, Zong-Wan Mao, Hong-Ke Liu, Peter J. Sadler

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2′-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).

Original languageEnglish
Pages (from-to)17450-17461
Number of pages12
JournalInorganic Chemistry
Volume60
Issue number23
Early online date9 Sep 2021
DOIs
Publication statusPublished - 6 Dec 2021

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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