期刊
INORGANIC CHEMISTRY
卷 60, 期 23, 页码 17450-17461出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.1c00241
关键词
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资金
- NSFC [22077066, 21771109, 21778033, 21701195, 21837006, 21977052]
- NSF of Jiangsu Province [BK20171472]
- ERC [247450]
- EPSRC [EP/F034210/1, EP/P030572/1, EP/P001459, EP/T021675]
- Anglo American Platinum
- Severo Ochoa Centres of Excellence Programme
- Spanish State Research Agency [CEX2018-000867-S]
Half-sandwich Os-arene complexes exhibit promising anticancer activity, especially the OsCUR-2 complex, which shows remarkable photocytotoxicity towards a range of cancer cell lines and has the potential for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT). The photochemistry of these complexes involves selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) under blue light or UVA excitation.
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(eta(6)-p-cymene) (Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(eta(6)-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(eta(6)-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(eta(6)-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 mu M, 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).
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