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Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex

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...

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Autores principales: Lanquist, Austin P., Gupta, Sayak, Al-Afyouni, Kathlyn F., Al-Afyouni, Malik, Kodanko, Jeremy J., Turro, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457392/
https://www.ncbi.nlm.nih.gov/pubmed/34667571
http://dx.doi.org/10.1039/d1sc03213e
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author Lanquist, Austin P.
Gupta, Sayak
Al-Afyouni, Kathlyn F.
Al-Afyouni, Malik
Kodanko, Jeremy J.
Turro, Claudia
author_facet Lanquist, Austin P.
Gupta, Sayak
Al-Afyouni, Kathlyn F.
Al-Afyouni, Malik
Kodanko, Jeremy J.
Turro, Claudia
author_sort Lanquist, Austin P.
collection PubMed
description 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 pK(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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spelling pubmed-84573922021-10-18 Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex Lanquist, Austin P. Gupta, Sayak Al-Afyouni, Kathlyn F. Al-Afyouni, Malik Kodanko, Jeremy J. Turro, Claudia Chem Sci Chemistry 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 pK(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. The Royal Society of Chemistry 2021-08-16 /pmc/articles/PMC8457392/ /pubmed/34667571 http://dx.doi.org/10.1039/d1sc03213e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Lanquist, Austin P.
Gupta, Sayak
Al-Afyouni, Kathlyn F.
Al-Afyouni, Malik
Kodanko, Jeremy J.
Turro, Claudia
Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title_full Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title_fullStr Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title_full_unstemmed Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title_short Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex
title_sort trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in ru(ii) complex
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457392/
https://www.ncbi.nlm.nih.gov/pubmed/34667571
http://dx.doi.org/10.1039/d1sc03213e
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