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A series of five ruthenium complexes containing triphenyl phosphine groups known to enhance both cellular penetration and photoinduced ligand exchange, cis -[Ru(bpy) 2 (P( p -R-Ph) 3 )(CH 3 CN)] 2+ , where bpy = 2,2′-bipyridine and P( p -R-Ph) 3 represent para -substituted triphenylphosphine ligands with R = –OCH 3 (1), –CH 3 (2) –H (3), –F (4), and –CF 3 (5), were synthesized and characterized. The photolysis of 1–5 in water with visible light ( λ irr ≥ 395 nm) results in the substitution of the coordinated acetonitrile with a solvent molecule, generating the corresponding aqua complex as the single photoproduct. A 3-fold variation in quantum yield was measured with 400 nm irradiation, Φ 400 , where 1 is the most efficient with a Φ 400 = 0.076(2), and 5 the least photoactive complex, with Φ 400 = 0.026(2). This trend is unexpected based on the red-shifted metal-to-ligand charge transfer (MLCT) absorption of 1 as compared to that of 5, but can be correlated to the substituent Hammett para parameters and p K a values of the ancillary phosphine ligands. Complexes 1–5 are not toxic towards the triple negative breast cancer cell line MDA-MB-231 in the dark, but 3 and 5 are >4.2 and >19-fold more cytotoxic upon irradiation with blue light, respectively. A number of experiments point to apoptosis, and not to necrosis or necroptosis, as the mechanism of cell death by 5 upon irradiation. These findings provide a foundation for understanding the role of phosphine ligands on photoinduced ligand substitution and show the enhancement afforded by –CF 3 groups on photochemotherapy, which will aid the future design of photocages for photochemotherapeutic drug delivery.
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Unlocking the Potential of Ru(II) Dual‐action Compounds with the Power of the Heavy‐atom Effect †
ABSTRACT We report the synthesis, photochemical and biological characterization of two new Ru(II) photoactivated complexes based on [Ru(tpy)(Me2bpy)(L)]2+(tpy = 2,2':6',2''‐terpyridine, Me2bpy = 6,6'‐dimethyl‐2,2'‐bipyridine), where L = pyridyl‐BODIPY (pyBOD). Two pyBOD ligands were prepared bearing flanking hydrogen or iodine atoms. Ru(II)‐bound BODIPY dyes show a red‐shift of absorption maxima relative to the free dyes and undergo photodissociation of BODIPY ligands with green light irradiation. Addition of iodine into the BODIPY ligand facilitates intersystem crossing, which leads to efficient singlet oxygen production in the free dye, but also enhances quantum yield of release of the BODIPY ligand from Ru(II). This represents the first report of a strategy to enhance photodissociation quantum yields through the heavy‐atom effect in Ru(II) complexes. Furthermore, Ru(II)‐bound BODIPY dyes display fluorescence turn‐on once released, with a lead analog showing nanomolar EC50values against triple negative breast cancer cells, >100‐fold phototherapeutic indexes under green light irradiation, and higher selectivity toward cancer cells as compared to normal cells than the corresponding free BODIPY photosensitizer. Conventional Ru(II) photoactivated complexes require nonbiorthogonal blue light for activation and rarely show submicromolar potency to achieve cell death. Our study represents an avenue for the improved photochemistry and potency of future Ru(II) complexes.
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- Award ID(s):
- 2102508
- PAR ID:
- 10364019
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Photochemistry and Photobiology
- Volume:
- 98
- Issue:
- 2
- ISSN:
- 0031-8655
- Page Range / eLocation ID:
- p. 378-388
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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