Síntese de complexos de Ru(II) luminescentes: aplicações no combate à doença de Alzheimer
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/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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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/ufscar/15505.https://repositorio.ufscar.br/handle/ufscar/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/bitstream/ufscar/15505/1/Tese_Marlon%20Augusto%20Profeta%20de%20Almeida_final.pdff0116ee7962bf9f0b3705663a5b83120MD51Carta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdfCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdfapplication/pdf359061https://repositorio.ufscar.br/bitstream/ufscar/15505/2/Carta-Comprovante_Homologacao-Marlon%20Augusto%20Profeta%20de%20Almeida.pdf7a81e2e1bf2adb32154cf91ecabb3bedMD52CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufscar.br/bitstream/ufscar/15505/3/license_rdfe39d27027a6cc9cb039ad269a5db8e34MD53TEXTTese_Marlon Augusto Profeta de Almeida_final.pdf.txtTese_Marlon Augusto Profeta de Almeida_final.pdf.txtExtracted texttext/plain181625https://repositorio.ufscar.br/bitstream/ufscar/15505/4/Tese_Marlon%20Augusto%20Profeta%20de%20Almeida_final.pdf.txt66dedda1c4ca575247142b04ac5d83aaMD54Carta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.txtCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.txtExtracted texttext/plain1417https://repositorio.ufscar.br/bitstream/ufscar/15505/6/Carta-Comprovante_Homologacao-Marlon%20Augusto%20Profeta%20de%20Almeida.pdf.txt210b0eec0139467873f2ac9fee4d30b2MD56THUMBNAILTese_Marlon Augusto Profeta de Almeida_final.pdf.jpgTese_Marlon Augusto Profeta de Almeida_final.pdf.jpgIM Thumbnailimage/jpeg9502https://repositorio.ufscar.br/bitstream/ufscar/15505/5/Tese_Marlon%20Augusto%20Profeta%20de%20Almeida_final.pdf.jpg2b7ef3209fb927e517beea2f54f4c9f5MD55Carta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.jpgCarta-Comprovante_Homologacao-Marlon Augusto Profeta de Almeida.pdf.jpgIM Thumbnailimage/jpeg12269https://repositorio.ufscar.br/bitstream/ufscar/15505/7/Carta-Comprovante_Homologacao-Marlon%20Augusto%20Profeta%20de%20Almeida.pdf.jpgd675ae886998cb4d015ed952057717c3MD57ufscar/155052023-09-18 18:32:22.993oai:repositorio.ufscar.br:ufscar/15505Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:32:22Repositório 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 |
dc.date.available.fl_str_mv |
2022-01-26T12:28:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
status_str |
publishedVersion |
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/ufscar/15505. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/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/ufscar/15505. |
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https://repositorio.ufscar.br/handle/ufscar/15505 |
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Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de São Carlos Câmpus São Carlos |
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Programa de Pós-Graduação em Química - PPGQ |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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