Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2024 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/173274 |
Resumo: | Funding Information: This work was supported by the MCIN/AEI of Spain (projects PID2021-127187OB-C21 and PID2021-127187OB-C22). The PhD students acknowledge their predoctoral grants to Universidad de Burgos (J. S. V., 2019/00002/008/001) and University of Girona (C. B., IFUdG 2021). Publisher Copyright: © 2024 The Royal Society of Chemistry. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligandsInorganic ChemistrySDG 3 - Good Health and Well-beingFunding Information: This work was supported by the MCIN/AEI of Spain (projects PID2021-127187OB-C21 and PID2021-127187OB-C22). The PhD students acknowledge their predoctoral grants to Universidad de Burgos (J. S. V., 2019/00002/008/001) and University of Girona (C. B., IFUdG 2021). Publisher Copyright: © 2024 The Royal Society of Chemistry.In this work we disclose a new family of biscyclometallated Ir(iii) complexes of the general formula [Ir(C^N)2(N^N)]Cl (IrL1-IrL5), where HC^N is 1-phenyl-β-carboline and N^N ligands (L1-L5) are different diimine ligands that differ from each other in the number of aromatic rings fused to the bipyridine scaffold. The photophysical properties of IrL1-IrL5 were thoroughly studied, and theoretical calculations were performed for a deeper comprehension of the respective variations along the series. All complexes exhibited high photostability under blue light irradiation. An increase in the number of aromatic rings led to a reduction in the HOMO-LUMO band gap causing a red-shift in the absorbance bands. Although all the complexes generated singlet oxygen (1O2) in aerated aqueous solutions through a photocatalytic process, IrL5 was by far the most efficient photosensitizer. Consequently, IrL5 was highly active in the photocatalytic oxidation of NADH. The formation of aggregates in DMSO at a high concentration (25 mM) was confirmed using different techniques, but was proved to be negligible in the concentration range of biological experiments. Moreover, ICP-MS studies proved that the cellular uptake of IrL2 and IrL3 is much better relative to that of IrL1, IrL4 and IrL5. The antiproliferative activity of IrL1-IrL5 was investigated in the dark and under blue light irradiation against different cancer cell lines. Complexes IrL1-IrL4 were found to be cytotoxic under dark conditions, while IrL5 turned out to be weakly cytotoxic. Despite the low cellular uptake of IrL5, this derivative exhibited a high increase of cytotoxicity upon blue light irradiation resulting in photocytotoxicity indexes (PI) up to 38. IrL1-IrL4 showed lower photocytotoxicity indexes ranging from 1.3 to 17.0. Haemolytic experiments corroborated the compatibility of our complexes with red blood cells. Confocal microscopy studies proved their accumulation in mitochondria, leading to mitochondrial membrane depolarization, and ruled out their localization in lysosomes. Overall, the mitochondria-targeted activity of IrL5, which inhibits considerably the viability of cancer cells upon blue light irradiation, allows us to outline this PS as a new alternative to traditional chemotherapeutic agents.LAQV@REQUIMTEDQ - Departamento de QuímicaRUNSanz-Villafruela, JuanBermejo-Casadesús, CristinaMartínez-Alonso, MartaMoro, ArturLima, João C.Massaguer, AnnaEspino, Gustavo2024-10-09T22:39:49Z2024-07-092024-07-09T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17application/pdfhttp://hdl.handle.net/10362/173274eng1477-9226PURE: 96233362https://doi.org/10.1039/d4dt00390jinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-10-14T01:40:59Zoai:run.unl.pt:10362/173274Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-10-14T01:40:59Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| title |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| spellingShingle |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands Sanz-Villafruela, Juan Inorganic Chemistry SDG 3 - Good Health and Well-being |
| title_short |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| title_full |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| title_fullStr |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| title_full_unstemmed |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| title_sort |
Towards efficient Ir(iii) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands |
| author |
Sanz-Villafruela, Juan |
| author_facet |
Sanz-Villafruela, Juan Bermejo-Casadesús, Cristina Martínez-Alonso, Marta Moro, Artur Lima, João C. Massaguer, Anna Espino, Gustavo |
| author_role |
author |
| author2 |
Bermejo-Casadesús, Cristina Martínez-Alonso, Marta Moro, Artur Lima, João C. Massaguer, Anna Espino, Gustavo |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
LAQV@REQUIMTE DQ - Departamento de Química RUN |
| dc.contributor.author.fl_str_mv |
Sanz-Villafruela, Juan Bermejo-Casadesús, Cristina Martínez-Alonso, Marta Moro, Artur Lima, João C. Massaguer, Anna Espino, Gustavo |
| dc.subject.por.fl_str_mv |
Inorganic Chemistry SDG 3 - Good Health and Well-being |
| topic |
Inorganic Chemistry SDG 3 - Good Health and Well-being |
| description |
Funding Information: This work was supported by the MCIN/AEI of Spain (projects PID2021-127187OB-C21 and PID2021-127187OB-C22). The PhD students acknowledge their predoctoral grants to Universidad de Burgos (J. S. V., 2019/00002/008/001) and University of Girona (C. B., IFUdG 2021). Publisher Copyright: © 2024 The Royal Society of Chemistry. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-10-09T22:39:49Z 2024-07-09 2024-07-09T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/173274 |
| url |
http://hdl.handle.net/10362/173274 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1477-9226 PURE: 96233362 https://doi.org/10.1039/d4dt00390j |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
17 application/pdf |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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mluisa.alvim@gmail.com |
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1817548597332279296 |