1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional
Ano de defesa: | 2021 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/23045 |
Resumo: | Taking into account potential bioactive, photophysical and redox-active properties of N-heterocycles and of their N-oxides, a 40 inedit benzofuroxan- or 2,2-dimethyl-2H-benzimidazole-1,3-dioxide- bound 1,2,3-triazolyl-1,2,4-oxadiazoles library was prepared. Employing TBTU as a reagent and DBU as base resulted in a one-pot synthesis with satisfactory yields (49-93%) at room temperature, and in easy purification of the products, followed by characterization by means of 1H and 13C NMR, HRMS and X-ray diffraction. Two examples were reactive towards thiophenol, suggesting that interaction with thiols in biological medium is possible. In both situations, thiophenol was oxidized to its corresponding disulphide, the benzofuroxan derivative displaying selectivity for basic medium. One resulting ortho-dioxime was isolated and characterized, as well as a benzofurazan, its decomposition product. In silico studies at DFT level helped the understanding of benzofuroxan derivatives tautomerization, their geometry and their HOMO and LUMO orbitals. Molecular docking procedures estimated promising interactions between some compounds and the main protease of SARS-CoV-2. Moreover, antimicrobial, cytotoxicity and photophysical/ electrochemical properties of the compounds were carried out in collaboration with other research groups. |
id |
UFSM-20_88c4fd1bb73d5fa4888d6f8b3b37b981 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/23045 |
network_acronym_str |
UFSM-20 |
network_name_str |
Manancial - Repositório Digital da UFSM |
repository_id_str |
|
spelling |
2021-11-29T15:04:50Z2021-11-29T15:04:50Z2021-12-18http://repositorio.ufsm.br/handle/1/23045Taking into account potential bioactive, photophysical and redox-active properties of N-heterocycles and of their N-oxides, a 40 inedit benzofuroxan- or 2,2-dimethyl-2H-benzimidazole-1,3-dioxide- bound 1,2,3-triazolyl-1,2,4-oxadiazoles library was prepared. Employing TBTU as a reagent and DBU as base resulted in a one-pot synthesis with satisfactory yields (49-93%) at room temperature, and in easy purification of the products, followed by characterization by means of 1H and 13C NMR, HRMS and X-ray diffraction. Two examples were reactive towards thiophenol, suggesting that interaction with thiols in biological medium is possible. In both situations, thiophenol was oxidized to its corresponding disulphide, the benzofuroxan derivative displaying selectivity for basic medium. One resulting ortho-dioxime was isolated and characterized, as well as a benzofurazan, its decomposition product. In silico studies at DFT level helped the understanding of benzofuroxan derivatives tautomerization, their geometry and their HOMO and LUMO orbitals. Molecular docking procedures estimated promising interactions between some compounds and the main protease of SARS-CoV-2. Moreover, antimicrobial, cytotoxicity and photophysical/ electrochemical properties of the compounds were carried out in collaboration with other research groups.Tendo em mente potenciais propriedades bioativas, fotofísicas e redox-ativas de N-heterociclos e de N-óxidos heterocíclicos, sintetizou-se uma biblioteca de 40 compostos inéditos derivados de 1,2,3-triazolil-1,2,4-oxadiazóis conectados a uma unidade benzofuroxano ou 1,3-dióxido de 2,2-dimetil-2H-benzimidazol. A utilização do reagente TBTU e da base DBU resultou em uma síntese one-pot com rendimentos satisfatórios (49 – 93 %) à temperatura ambiente, e de fácil purificação dos produtos, os quais foram caracterizados por RMN de 1H e de 13C, por HRMS e por difração de raios-X. Dois exemplos foram reativos frente ao tiofenol, sugerindo que uma interação com tióis em meio biológico é possível. Nos dois casos, houve oxidação do tiofenol ao respectivo dissulfeto, sendo que o derivado de benzofuroxano apresentou seletividade para reação em meio básico. Uma orto-dioxima resultante foi isolada e caracterizada, bem como um benzofurazano, seu produto de degradação. Estudos in silico a nível de DFT auxiliaram na compreensão da tautomerização dos derivados de benzofuroxano, de sua geometria e dos orbitais HOMO e LUMO dos compostos. Procedimentos de Ancoragem Molecular estimaram interações promissoras entre alguns compostos e a protease principal do SARS-CoV-2. Por fim, procedeu-se com a avaliação antimicrobiana, de citotoxicidade e de propriedades fotofísicas e eletroquímicas dos compostos em parceria com outros grupos de pesquisa.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em QuímicaUFSMBrasilQuímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessFuroxanosOxadiazóisTriazóisOxidaçãoModelagem molecularFuroxansOxadiazolesTriazolesOxidationMolecular modelingCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional1,2,3-triazolyl-1,2,4-oxadiazoles derivatives of benzo-fused N-heterocycle-N-oxides: synthesis, physical-chemical characterization, reactivity and computational studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisDornelles, Lucianohttp://lattes.cnpq.br/7629319262073140Iglesias, Bernardo AlmeidaDalcol, Ionara irionWolf, LucasSchwab, Ricardo Samuelhttp://lattes.cnpq.br/2787457529574646Mayer, João Cândido Pilar1006000000006006006006006006b4b1c8a-fdd1-49f0-a8ce-2d891b6579b620fb5647-f598-47ba-8c9e-b9d8ffa5fe75483d6d0c-e419-454b-b413-1a51673258c3a40bb239-8ee1-458e-9d6a-c027ca35d1ff7877a633-a1d5-4f09-9be9-662efe3b30442fb6c954-4a85-4094-b7e7-df6a5318f943reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/23045/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALTES_PPGQUIMICA_2021_MAYER_JOÃO.pdfTES_PPGQUIMICA_2021_MAYER_JOÃO.pdfTese de Doutoradoapplication/pdf19851824http://repositorio.ufsm.br/bitstream/1/23045/1/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf3b4e93b2e92a0ace8f1245204e5b7908MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/23045/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52TEXTTES_PPGQUIMICA_2021_MAYER_JOÃO.pdf.txtTES_PPGQUIMICA_2021_MAYER_JOÃO.pdf.txtExtracted texttext/plain507644http://repositorio.ufsm.br/bitstream/1/23045/4/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf.txt4db68a5d2518ef4d753e8df62ace80bbMD54THUMBNAILTES_PPGQUIMICA_2021_MAYER_JOÃO.pdf.jpgTES_PPGQUIMICA_2021_MAYER_JOÃO.pdf.jpgIM Thumbnailimage/jpeg4820http://repositorio.ufsm.br/bitstream/1/23045/5/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf.jpg9467d50e25e26264dc040851e031385fMD551/230452021-12-30 10:49:44.846oai:repositorio.ufsm.br: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ório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132021-12-30T13:49:44Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
dc.title.alternative.eng.fl_str_mv |
1,2,3-triazolyl-1,2,4-oxadiazoles derivatives of benzo-fused N-heterocycle-N-oxides: synthesis, physical-chemical characterization, reactivity and computational study |
title |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
spellingShingle |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional Mayer, João Cândido Pilar Furoxanos Oxadiazóis Triazóis Oxidação Modelagem molecular Furoxans Oxadiazoles Triazoles Oxidation Molecular modeling CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
title_full |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
title_fullStr |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
title_full_unstemmed |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
title_sort |
1,2,3-triazolil-1,2,4-oxadiazóis derivados de N-óxidos N-heterocíclicos benzofundidos: síntese, caracterização físico-química, reatividade e estudo computacional |
author |
Mayer, João Cândido Pilar |
author_facet |
Mayer, João Cândido Pilar |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Dornelles, Luciano |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7629319262073140 |
dc.contributor.referee1.fl_str_mv |
Iglesias, Bernardo Almeida |
dc.contributor.referee2.fl_str_mv |
Dalcol, Ionara irion |
dc.contributor.referee3.fl_str_mv |
Wolf, Lucas |
dc.contributor.referee4.fl_str_mv |
Schwab, Ricardo Samuel |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2787457529574646 |
dc.contributor.author.fl_str_mv |
Mayer, João Cândido Pilar |
contributor_str_mv |
Dornelles, Luciano Iglesias, Bernardo Almeida Dalcol, Ionara irion Wolf, Lucas Schwab, Ricardo Samuel |
dc.subject.por.fl_str_mv |
Furoxanos Oxadiazóis Triazóis Oxidação Modelagem molecular |
topic |
Furoxanos Oxadiazóis Triazóis Oxidação Modelagem molecular Furoxans Oxadiazoles Triazoles Oxidation Molecular modeling CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Furoxans Oxadiazoles Triazoles Oxidation Molecular modeling |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Taking into account potential bioactive, photophysical and redox-active properties of N-heterocycles and of their N-oxides, a 40 inedit benzofuroxan- or 2,2-dimethyl-2H-benzimidazole-1,3-dioxide- bound 1,2,3-triazolyl-1,2,4-oxadiazoles library was prepared. Employing TBTU as a reagent and DBU as base resulted in a one-pot synthesis with satisfactory yields (49-93%) at room temperature, and in easy purification of the products, followed by characterization by means of 1H and 13C NMR, HRMS and X-ray diffraction. Two examples were reactive towards thiophenol, suggesting that interaction with thiols in biological medium is possible. In both situations, thiophenol was oxidized to its corresponding disulphide, the benzofuroxan derivative displaying selectivity for basic medium. One resulting ortho-dioxime was isolated and characterized, as well as a benzofurazan, its decomposition product. In silico studies at DFT level helped the understanding of benzofuroxan derivatives tautomerization, their geometry and their HOMO and LUMO orbitals. Molecular docking procedures estimated promising interactions between some compounds and the main protease of SARS-CoV-2. Moreover, antimicrobial, cytotoxicity and photophysical/ electrochemical properties of the compounds were carried out in collaboration with other research groups. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-29T15:04:50Z |
dc.date.available.fl_str_mv |
2021-11-29T15:04:50Z |
dc.date.issued.fl_str_mv |
2021-12-18 |
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 |
http://repositorio.ufsm.br/handle/1/23045 |
url |
http://repositorio.ufsm.br/handle/1/23045 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
100600000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
6b4b1c8a-fdd1-49f0-a8ce-2d891b6579b6 20fb5647-f598-47ba-8c9e-b9d8ffa5fe75 483d6d0c-e419-454b-b413-1a51673258c3 a40bb239-8ee1-458e-9d6a-c027ca35d1ff 7877a633-a1d5-4f09-9be9-662efe3b3044 2fb6c954-4a85-4094-b7e7-df6a5318f943 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Química |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/23045/3/license.txt http://repositorio.ufsm.br/bitstream/1/23045/1/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf http://repositorio.ufsm.br/bitstream/1/23045/2/license_rdf http://repositorio.ufsm.br/bitstream/1/23045/4/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf.txt http://repositorio.ufsm.br/bitstream/1/23045/5/TES_PPGQUIMICA_2021_MAYER_JO%c3%83O.pdf.jpg |
bitstream.checksum.fl_str_mv |
2f0571ecee68693bd5cd3f17c1e075df 3b4e93b2e92a0ace8f1245204e5b7908 4460e5956bc1d1639be9ae6146a50347 4db68a5d2518ef4d753e8df62ace80bb 9467d50e25e26264dc040851e031385f |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
|
_version_ |
1794524422984433664 |