Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/29891 |
Resumo: | Water-soluble cationic Mn(III) porphyrins derived from 2-N-pyridylporphyrins were originally developed as potent mimics of superoxide dismutase (SOD) enzymes, catalysts of peroxynitrite decomposition, and later proved to be efficient redox-active therapeutic agents. In this thesis, three independent studies were developed, focusing on Mn-Porphyrins based on N-alkylpyridylporphyrins and N-alkylquinolylporphyrins. Initially, the first study was carried out on the kinetics of thermal degradation (under isothermal and non-isothermal conditions) of a redox-active MnP, MnTE-2-PyPCl5, being the compound of choice in most exploratory preclinical studies, for having an established reputation for the design of bioavailable SOD mimics. In this study, a multilayer neural network (MLP) allowed the simultaneous evaluation of ten kinetic models; activation energy values calculated from isothermal and non-isothermal data agree with each other and are consistent with the high thermal stability of MnTE-2-PyPCl5 observed in the solid state. The t90% shelf-life value at 25 °C, estimated from the isothermal decomposition data, was approximately 17 years. Additionally, a spectrophotometric protocol was developed to determine the molar absorptivity of MnTE-2-PyPCl5 using thermogravimetric analysis (TG) and differential thermal analysis (DTA) as a tool. The conditions for the determination of molar absorptivity from the thermal analysis dehydration step were established. Finally, the last study concerns the attempt to develop a new class of porphyrins containing the 2-quinoline group. Some difficulties were encountered during its execution: among them, the non-reproducibility of the syntheses, which was related to the quality of the commercial 2-quinolinecarboxaldehyde. Despite the difficulties, synthetic routes were developed to obtain H2T-2-QnP, H2TM-2-QnP4+ and MnTM-2-QnP5+. The compounds were isolated in 5, 68 and 78 % yields, respectively. |
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Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativosQuímicaMn-porfirinasCinética de decomposiçãoDeterminação de absortividade molarSíntese de porfirinas - Grupo 2-quinolilMn-porphyrinsDecomposition kineticsDetermination of molar absorptivitySynthesis of porphyrins containing the 2-quinolyl groupCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAWater-soluble cationic Mn(III) porphyrins derived from 2-N-pyridylporphyrins were originally developed as potent mimics of superoxide dismutase (SOD) enzymes, catalysts of peroxynitrite decomposition, and later proved to be efficient redox-active therapeutic agents. In this thesis, three independent studies were developed, focusing on Mn-Porphyrins based on N-alkylpyridylporphyrins and N-alkylquinolylporphyrins. Initially, the first study was carried out on the kinetics of thermal degradation (under isothermal and non-isothermal conditions) of a redox-active MnP, MnTE-2-PyPCl5, being the compound of choice in most exploratory preclinical studies, for having an established reputation for the design of bioavailable SOD mimics. In this study, a multilayer neural network (MLP) allowed the simultaneous evaluation of ten kinetic models; activation energy values calculated from isothermal and non-isothermal data agree with each other and are consistent with the high thermal stability of MnTE-2-PyPCl5 observed in the solid state. The t90% shelf-life value at 25 °C, estimated from the isothermal decomposition data, was approximately 17 years. Additionally, a spectrophotometric protocol was developed to determine the molar absorptivity of MnTE-2-PyPCl5 using thermogravimetric analysis (TG) and differential thermal analysis (DTA) as a tool. The conditions for the determination of molar absorptivity from the thermal analysis dehydration step were established. Finally, the last study concerns the attempt to develop a new class of porphyrins containing the 2-quinoline group. Some difficulties were encountered during its execution: among them, the non-reproducibility of the syntheses, which was related to the quality of the commercial 2-quinolinecarboxaldehyde. Despite the difficulties, synthetic routes were developed to obtain H2T-2-QnP, H2TM-2-QnP4+ and MnTM-2-QnP5+. The compounds were isolated in 5, 68 and 78 % yields, respectively.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqPorfirinas de Mn(III) catiônicas hidrossolúveis e derivadas das 2-N-piridilporfirinas foram originalmente desenvolvidas como potentes mímicos das enzimas superóxido dismutase (SOD), catalisadores de decomposição de peroxinitrito e, mais tarde, provaram ser agentes terapêuticos redox-ativos eficientes. Nesta tese foram desenvolvidos três estudos independentes, tendo como foco as Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas. Inicialmente, realizou-se o primeiro estudo sobre a cinética de degradação térmica (sob condições isotérmicas e não isotérmicas) de uma MnP redox-ativa, a MnTE-2-PyPCl5, sendo o composto de escolha da maioria dos estudos pré-clínicos exploratórios, por ter uma reputação estabelecida para o design de mímicos SOD biodisponíveis. Nesse estudo, uma rede neural multicamadas (MLP) permitiu a avaliação simultânea de dez modelos cinéticos; os valores de energia de ativação calculados a partir de dados isotérmicos e não isotérmicos concordam entre si e são consistentes com a alta estabilidade térmica da MnTE-2-PyPCl5 observada no estado sólido. O valor de vida útil de t90% a 25 °C estimado a partir dos dados de decomposição isotérmica foi de aproximadamente 17 anos. Adicionalmente, foi desenvolvido um protocolo espectrofotométrico para a determinação da absortividade molar da MnTE-2-PyPCl5 assistida por análises termogravimétricas (TG) e análise térmica diferencial (DTA) como ferramentas. As condições para a determinação da absortividade molar a partir da etapa de desidratação de análise térmica foram estabelecidas. Por fim, o último estudo diz respeito à tentativa de desenvolver uma nova classe de porfirinas contendo o grupo 2-quinolina. Algumas dificuldades foram enfrentadas durante a sua realização, dentre elas, destaca-se a não reprodutibilidade das sínteses, que foi associada à qualidade do 2-quinolinacarboxaldeído comercial. Apesar das dificuldades, rotas sintéticas foram desenvolvidas para a obtenção da H2T-2-QnP, H2TM-2-QnP4+ e MnTM-2-QnP5+, isoladas com rendimentos de 5, 68 e 78 %, respectivamente.Universidade Federal da ParaíbaBrasilQuímicaPrograma de Pós-Graduação em QuímicaUFPBRebouças, Júlio Santoshttp://lattes.cnpq.br/0305007181787906Maia, Clarissa Gomes de Carvalho2024-03-18T13:19:47Z2023-06-202024-03-18T13:19:47Z2023-02-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/29891porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2024-03-19T06:03:08Zoai:repositorio.ufpb.br:123456789/29891Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2024-03-19T06:03:08Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
title |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
spellingShingle |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos Maia, Clarissa Gomes de Carvalho Química Mn-porfirinas Cinética de decomposição Determinação de absortividade molar Síntese de porfirinas - Grupo 2-quinolil Mn-porphyrins Decomposition kinetics Determination of molar absorptivity Synthesis of porphyrins containing the 2-quinolyl group CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
title_full |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
title_fullStr |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
title_full_unstemmed |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
title_sort |
Desenvolvimento de Mn-Porfirinas à base de N-alquilpiridilporfirinas e N-alquilquinolilporfirinas como candidatos a agentes terapêuticos redox-ativos |
author |
Maia, Clarissa Gomes de Carvalho |
author_facet |
Maia, Clarissa Gomes de Carvalho |
author_role |
author |
dc.contributor.none.fl_str_mv |
Rebouças, Júlio Santos http://lattes.cnpq.br/0305007181787906 |
dc.contributor.author.fl_str_mv |
Maia, Clarissa Gomes de Carvalho |
dc.subject.por.fl_str_mv |
Química Mn-porfirinas Cinética de decomposição Determinação de absortividade molar Síntese de porfirinas - Grupo 2-quinolil Mn-porphyrins Decomposition kinetics Determination of molar absorptivity Synthesis of porphyrins containing the 2-quinolyl group CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
topic |
Química Mn-porfirinas Cinética de decomposição Determinação de absortividade molar Síntese de porfirinas - Grupo 2-quinolil Mn-porphyrins Decomposition kinetics Determination of molar absorptivity Synthesis of porphyrins containing the 2-quinolyl group CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Water-soluble cationic Mn(III) porphyrins derived from 2-N-pyridylporphyrins were originally developed as potent mimics of superoxide dismutase (SOD) enzymes, catalysts of peroxynitrite decomposition, and later proved to be efficient redox-active therapeutic agents. In this thesis, three independent studies were developed, focusing on Mn-Porphyrins based on N-alkylpyridylporphyrins and N-alkylquinolylporphyrins. Initially, the first study was carried out on the kinetics of thermal degradation (under isothermal and non-isothermal conditions) of a redox-active MnP, MnTE-2-PyPCl5, being the compound of choice in most exploratory preclinical studies, for having an established reputation for the design of bioavailable SOD mimics. In this study, a multilayer neural network (MLP) allowed the simultaneous evaluation of ten kinetic models; activation energy values calculated from isothermal and non-isothermal data agree with each other and are consistent with the high thermal stability of MnTE-2-PyPCl5 observed in the solid state. The t90% shelf-life value at 25 °C, estimated from the isothermal decomposition data, was approximately 17 years. Additionally, a spectrophotometric protocol was developed to determine the molar absorptivity of MnTE-2-PyPCl5 using thermogravimetric analysis (TG) and differential thermal analysis (DTA) as a tool. The conditions for the determination of molar absorptivity from the thermal analysis dehydration step were established. Finally, the last study concerns the attempt to develop a new class of porphyrins containing the 2-quinoline group. Some difficulties were encountered during its execution: among them, the non-reproducibility of the syntheses, which was related to the quality of the commercial 2-quinolinecarboxaldehyde. Despite the difficulties, synthetic routes were developed to obtain H2T-2-QnP, H2TM-2-QnP4+ and MnTM-2-QnP5+. The compounds were isolated in 5, 68 and 78 % yields, respectively. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06-20 2023-02-14 2024-03-18T13:19:47Z 2024-03-18T13:19:47Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/29891 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/29891 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Química Programa de Pós-Graduação em Química UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Química Programa de Pós-Graduação em Química UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801843031233527808 |