Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Almeida, Marlon Augusto Profeta de
Orientador(a): Carlos, Rose Maria lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Câmpus São Carlos
Programa de Pós-Graduação: Programa de Pós-Graduação em Química - PPGQ
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/20.500.14289/15505
Resumo: Alzheimer’s disease (A.D) is the most common form of dementia affecting, especially, people with advanced age. There is no cure and the existing pharmaceuticals indicated for combating A.D act by inhibition of acetylcholinesterase enzyme (AChE), whose hyperactivity is related to the initial symptoms of the disease. This pharmaceuticals offer symptomatic and palliative treatments and are associated with several side effects. In this work two new Ru(II) compounds (RuFenGlic and RuEtPy) were designed to act as new AChE inhibitors. The complexes presented luminescence, being able to be used as luminescent probes for amyloid-β aggregation process which enables a potential diagnostic system. RuFenGlic complex showed poor inhibitory activity while RuEtPy complex showed inhibitory activity comparable to Galantamine drug. Furthermore, STD-1H-NMR analysis allowed inferring that Fen ligand of RuFenGlic complex and the EtPy ligand of RuEtPy complex are the most responsible for the inhibition observed for each complex. Photochemical properties of both complexes were studied in solution. RuFenGlic complex shows photostability when irradiated in wavelengths under its MLCT absorption band (420, 450, 520 nm). On the other hand, RuEtPy complex shows photosubstitution of the EtPy ligand when irradiated in the same wavelengths. The phenomenon is observed by MLCT shifts and sequential luminescence quenching after irradiation. Interestingly, this photochemical reaction for this complex reaches stabilization after 3 hours of irradiation, with substitution of only one of the EtPy ligands and luminescence quenching between 70 and 90% of the band, but never total quenching. This property can be explored for diagnose and treatment of cancer through photoactivatable chemotherapy (PACT).
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spelling Almeida, Marlon Augusto Profeta deCarlos, Rose Mariahttp://lattes.cnpq.br/1589143355309943http://lattes.cnpq.br/96218464977992218d98df91-6ba5-4a38-906c-f374fde5e2512022-01-26T12:28:38Z2022-01-26T12:28:38Z2021-12-17ALMEIDA, Marlon Augusto Profeta de. Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer. 2021. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/15505.https://repositorio.ufscar.br/handle/20.500.14289/15505Alzheimer’s disease (A.D) is the most common form of dementia affecting, especially, people with advanced age. There is no cure and the existing pharmaceuticals indicated for combating A.D act by inhibition of acetylcholinesterase enzyme (AChE), whose hyperactivity is related to the initial symptoms of the disease. This pharmaceuticals offer symptomatic and palliative treatments and are associated with several side effects. In this work two new Ru(II) compounds (RuFenGlic and RuEtPy) were designed to act as new AChE inhibitors. The complexes presented luminescence, being able to be used as luminescent probes for amyloid-β aggregation process which enables a potential diagnostic system. RuFenGlic complex showed poor inhibitory activity while RuEtPy complex showed inhibitory activity comparable to Galantamine drug. Furthermore, STD-1H-NMR analysis allowed inferring that Fen ligand of RuFenGlic complex and the EtPy ligand of RuEtPy complex are the most responsible for the inhibition observed for each complex. Photochemical properties of both complexes were studied in solution. RuFenGlic complex shows photostability when irradiated in wavelengths under its MLCT absorption band (420, 450, 520 nm). On the other hand, RuEtPy complex shows photosubstitution of the EtPy ligand when irradiated in the same wavelengths. The phenomenon is observed by MLCT shifts and sequential luminescence quenching after irradiation. Interestingly, this photochemical reaction for this complex reaches stabilization after 3 hours of irradiation, with substitution of only one of the EtPy ligands and luminescence quenching between 70 and 90% of the band, but never total quenching. This property can be explored for diagnose and treatment of cancer through photoactivatable chemotherapy (PACT).A doença de Alzheimer (D.A) é a forma mais comum de demência, atingindo, principalmente, pessoas de idade avançada. Ainda hoje não há cura, e os fármacos existentes indicados para combate à D.A. atuam inibindo da enzima acetilcolinesterase (AChE), cuja hiperatividade está relacionada aos sintomas iniciais da doença. São tratamentos sintomáticos e paliativos que estão associados a inúmeros efeitos colaterais. Neste trabalho foram propostos dois novos complexos de Ru(II) (RuFenGlic e RuEtPy) projetados para atuarem como novos inibidores da enzima AChE. Estes complexos apresentaram luminescência, podendo ser utilizados como sondas luminescentes do processo de agregação do peptídeo β-amilóide, podendo gerar uma alternativa de sistema para diagnóstico. O complexo RuFenGlic apresentou baixa atividade inibitória, enquanto o complexo RuEtPy apresentou resultados comparáveis à droga Galantamina. Além disso, análises por STD-1H-RMN permitiram inferir quais que o ligante fenantrolina no complexo RuFenGlic e os ligantes EtPy no complexo RuEtPy são os responsáveis pela inibição observada. Foram estudadas as propriedades fotoquímicas de ambos os complexos em solução. O complexo RuFenGlic apresenta estabilidade fotoquímica quando irradiado em comprimentos de onda compreendidos em sua banda de absorção MLCT (420, 450 e 520 nm) na ausência de O2. Em contrapardida, o complexo RuEtPy apresenta fotossubstituição dos ligantes EtPy quando irradiado em solução nos mesmos comprimentos de onda. Este fenômeno é observado pela deslocamento da banda de absorção MLCT e sucessivas supressões de sua banda de luminescência após irradiação. Interessantemente, a reação fotoquímica para este complexo atinge estabilidade após 3 horas de irradiação, com substituição de apenas um dos ligantes e supressão entre 70 e 90% da intensidade de luminescência, não ocorrendo supressão total. Esta propriedade pode ser explorada no tratamento e diagnóstico de doenças como câncer através da quimioterapia fotoativada.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: 88882.332778/2019-01porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessRu(II)Complexos luminescentesDoença de AlzheimerAcetilcolinesteraseLuminescent complexesAlzheimer's DiseaseActylcholinesteraseCIENCIAS EXATAS E DA TERRA::QUIMICASíntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de AlzheimerSynthesis of Ru(II) complexes: applications in the fight against Alzheimer's diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis60060081ea1b7e-7dcf-438f-a839-b8cab12c5740reponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTese_Marlon Augusto Profeta de Almeida_final.pdfTese_Marlon Augusto Profeta de Almeida_final.pdfapplication/pdf4972968https://repositorio.ufscar.br/bitstreams/3007c83e-ba58-461f-83c5-eb81176eb8c4/downloadf0116ee7962bf9f0b3705663a5b83120MD51trueAnonymousREADCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdfCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdfapplication/pdf359061https://repositorio.ufscar.br/bitstreams/f5fa517a-3442-4f50-82d5-d942f4658340/download7a81e2e1bf2adb32154cf91ecabb3bedMD52falseCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufscar.br/bitstreams/8de3fe23-9de1-4586-8b88-7c869f14d483/downloade39d27027a6cc9cb039ad269a5db8e34MD53falseAnonymousREADTEXTTese_Marlon Augusto Profeta de Almeida_final.pdf.txtTese_Marlon Augusto Profeta de Almeida_final.pdf.txtExtracted texttext/plain181625https://repositorio.ufscar.br/bitstreams/38fb99af-ecd9-443e-b92f-c4b94c54c780/download66dedda1c4ca575247142b04ac5d83aaMD58falseAnonymousREADCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.txtCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.txtExtracted texttext/plain1417https://repositorio.ufscar.br/bitstreams/1efe49b6-4fa2-4c77-9df3-8f6916b78620/download210b0eec0139467873f2ac9fee4d30b2MD510falseTHUMBNAILTese_Marlon Augusto Profeta de Almeida_final.pdf.jpgTese_Marlon Augusto Profeta de Almeida_final.pdf.jpgIM Thumbnailimage/jpeg9514https://repositorio.ufscar.br/bitstreams/78656c6a-bc3c-473a-9553-445ac83d7739/downloadfed0e35ff5db477e9cd7874130582a6cMD59falseAnonymousREADCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.jpgCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.jpgIM Thumbnailimage/jpeg12288https://repositorio.ufscar.br/bitstreams/28e18eeb-ba64-4c71-a911-607a7c11f2be/downloade1d8dc3876d1c05461a7118525b27a74MD511false20.500.14289/155052025-02-05 20:46:45.39http://creativecommons.org/licenses/by-nc-nd/3.0/br/Attribution-NonCommercial-NoDerivs 3.0 Brazilopen.accessoai:repositorio.ufscar.br:20.500.14289/15505https://repositorio.ufscar.brRepositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestrepositorio.sibi@ufscar.bropendoar:43222025-02-05T23:46:45Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
dc.title.alternative.eng.fl_str_mv Synthesis of Ru(II) complexes: applications in the fight against Alzheimer's disease
title Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
spellingShingle Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
Almeida, Marlon Augusto Profeta de
Ru(II)
Complexos luminescentes
Doença de Alzheimer
Acetilcolinesterase
Luminescent complexes
Alzheimer's Disease
Actylcholinesterase
CIENCIAS EXATAS E DA TERRA::QUIMICA
title_short Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
title_full Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
title_fullStr Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
title_full_unstemmed Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
title_sort Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
author Almeida, Marlon Augusto Profeta de
author_facet Almeida, Marlon Augusto Profeta de
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/9621846497799221
dc.contributor.author.fl_str_mv Almeida, Marlon Augusto Profeta de
dc.contributor.advisor1.fl_str_mv Carlos, Rose Maria
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1589143355309943
dc.contributor.authorID.fl_str_mv 8d98df91-6ba5-4a38-906c-f374fde5e251
contributor_str_mv Carlos, Rose Maria
dc.subject.por.fl_str_mv Ru(II)
Complexos luminescentes
Doença de Alzheimer
Acetilcolinesterase
topic Ru(II)
Complexos luminescentes
Doença de Alzheimer
Acetilcolinesterase
Luminescent complexes
Alzheimer's Disease
Actylcholinesterase
CIENCIAS EXATAS E DA TERRA::QUIMICA
dc.subject.eng.fl_str_mv Luminescent complexes
Alzheimer's Disease
Actylcholinesterase
dc.subject.cnpq.fl_str_mv CIENCIAS EXATAS E DA TERRA::QUIMICA
description Alzheimer’s disease (A.D) is the most common form of dementia affecting, especially, people with advanced age. There is no cure and the existing pharmaceuticals indicated for combating A.D act by inhibition of acetylcholinesterase enzyme (AChE), whose hyperactivity is related to the initial symptoms of the disease. This pharmaceuticals offer symptomatic and palliative treatments and are associated with several side effects. In this work two new Ru(II) compounds (RuFenGlic and RuEtPy) were designed to act as new AChE inhibitors. The complexes presented luminescence, being able to be used as luminescent probes for amyloid-β aggregation process which enables a potential diagnostic system. RuFenGlic complex showed poor inhibitory activity while RuEtPy complex showed inhibitory activity comparable to Galantamine drug. Furthermore, STD-1H-NMR analysis allowed inferring that Fen ligand of RuFenGlic complex and the EtPy ligand of RuEtPy complex are the most responsible for the inhibition observed for each complex. Photochemical properties of both complexes were studied in solution. RuFenGlic complex shows photostability when irradiated in wavelengths under its MLCT absorption band (420, 450, 520 nm). On the other hand, RuEtPy complex shows photosubstitution of the EtPy ligand when irradiated in the same wavelengths. The phenomenon is observed by MLCT shifts and sequential luminescence quenching after irradiation. Interestingly, this photochemical reaction for this complex reaches stabilization after 3 hours of irradiation, with substitution of only one of the EtPy ligands and luminescence quenching between 70 and 90% of the band, but never total quenching. This property can be explored for diagnose and treatment of cancer through photoactivatable chemotherapy (PACT).
publishDate 2021
dc.date.issued.fl_str_mv 2021-12-17
dc.date.accessioned.fl_str_mv 2022-01-26T12:28:38Z
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dc.identifier.citation.fl_str_mv ALMEIDA, Marlon Augusto Profeta de. Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer. 2021. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/15505.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/20.500.14289/15505
identifier_str_mv ALMEIDA, Marlon Augusto Profeta de. Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer. 2021. Tese (Doutorado em Química) – Universidade Federal de São Carlos, São Carlos, 2021. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/15505.
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