Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade
Ano de defesa: | 2013 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Não Informado pela instituição
|
Programa de Pós-Graduação: |
Pós-Graduação em Química
|
Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://ri.ufs.br/handle/riufs/6100 |
Resumo: | The doxorubicin (DOX) assumes a prominent position among the drugs widely applied in treatment human cancer. This chemotherapeutic presents efficiency in the regression of various neoplasms, although adverse reactions may occur. As a result several strategies have been developed to reduce the adverse effects caused by the continued use of DOX. One of these strategy is the incorporation of doxorubicin into MOF (Metal Organic Framework), since these materials can act as excellent carriers of drugs. The color change exhibited by doxorubicin as a function of pH, or even possibly when adsorbed in MOF, motivated the present work. This work consists in finding the possible factors that culminate in color change presented by DOX. This way, calculations involving the reactivity, and the UV/Vis spectroscopy of the possible tautomeric species of doxorubicin were performed. Thus, we applied the semiempirical methods, AM1, PM3, PM6 and RM1, and also DFT. We used the method INDO/S-CIS to calculate the spectroscopic of ground state geometries of various tautomer. All calculations revealed DOX1 as the most stable and DOX2 as the most unstable for protonated species. The method PM6 method was the more similar to the DFT by comparing the absorption spectra of DOX1 as well as the relative stabilities of the tautomers. The relative energies between deprotonated tautomers calculated by applied methods were smaller than protonated species, because the deprotonated tautomers denote considerable structural similarities between them. The reactivity study showed that the methods AM1 andPM3 exhibit the same qualitative behavior about the prediction of the transition state structure involved in each proton transfer reaction in the gas phase. The method PM6 resembled more to RM1, being the only exception was the conversion DOX1 → DOX4. Each absorption spectrum calculated from the optimized geometries with the DFT method to the different tautomeric species showed simply a band in the region of longer wavelengths (around 400 nm), which correspond to the visible region. In contrast, the absorption spectra obtained experimentally in acidic showed three bands in the region between 400 to 650 nm, thus cannot be attributed to a single predominant tautomer system, but the simultaneous contributing of all tautomers. The spectroscopic study of deprotonated tautomers, in order to simulate the effect of basic pH, suggests the presence also of the four tautomers deprotonated in the system, thus explaining the appearance of several absorption bands. The spectrum obtained at pH 7 can be explained from the presence of both doxorubicin protonated as deprotonated species. Thus, the application of computational tools proved to be able to elucidate some events associated with spectroscopy and reactivity of doxorubicin. |
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Florêncio e Silva, EdvonaldoCosta Júnior, Nivan Bezerra da2017-09-27T13:57:42Z2017-09-27T13:57:42Z2013-03-08https://ri.ufs.br/handle/riufs/6100The doxorubicin (DOX) assumes a prominent position among the drugs widely applied in treatment human cancer. This chemotherapeutic presents efficiency in the regression of various neoplasms, although adverse reactions may occur. As a result several strategies have been developed to reduce the adverse effects caused by the continued use of DOX. One of these strategy is the incorporation of doxorubicin into MOF (Metal Organic Framework), since these materials can act as excellent carriers of drugs. The color change exhibited by doxorubicin as a function of pH, or even possibly when adsorbed in MOF, motivated the present work. This work consists in finding the possible factors that culminate in color change presented by DOX. This way, calculations involving the reactivity, and the UV/Vis spectroscopy of the possible tautomeric species of doxorubicin were performed. Thus, we applied the semiempirical methods, AM1, PM3, PM6 and RM1, and also DFT. We used the method INDO/S-CIS to calculate the spectroscopic of ground state geometries of various tautomer. All calculations revealed DOX1 as the most stable and DOX2 as the most unstable for protonated species. The method PM6 method was the more similar to the DFT by comparing the absorption spectra of DOX1 as well as the relative stabilities of the tautomers. The relative energies between deprotonated tautomers calculated by applied methods were smaller than protonated species, because the deprotonated tautomers denote considerable structural similarities between them. The reactivity study showed that the methods AM1 andPM3 exhibit the same qualitative behavior about the prediction of the transition state structure involved in each proton transfer reaction in the gas phase. The method PM6 resembled more to RM1, being the only exception was the conversion DOX1 → DOX4. Each absorption spectrum calculated from the optimized geometries with the DFT method to the different tautomeric species showed simply a band in the region of longer wavelengths (around 400 nm), which correspond to the visible region. In contrast, the absorption spectra obtained experimentally in acidic showed three bands in the region between 400 to 650 nm, thus cannot be attributed to a single predominant tautomer system, but the simultaneous contributing of all tautomers. The spectroscopic study of deprotonated tautomers, in order to simulate the effect of basic pH, suggests the presence also of the four tautomers deprotonated in the system, thus explaining the appearance of several absorption bands. The spectrum obtained at pH 7 can be explained from the presence of both doxorubicin protonated as deprotonated species. Thus, the application of computational tools proved to be able to elucidate some events associated with spectroscopy and reactivity of doxorubicin.Dentre os fármacos largamente aplicados na prática oncológica humana, a doxorrubicina (DOX) assume uma posição de destaque. Apesar de este quimioterápico apresentar eficiência na regressão de várias neoplasias, reações adversas podem surgir. Em decorrência disso várias estratégias vêm sendo desenvolvidas para reduzir os efeitos adversos provocados pelo uso contínuo da DOX. Uma dessas estratégias consiste na incorporação da doxorrubicina em MOF s (Metal Organic Framework), uma vez que estes materiais podem atuar como excelentes carreadores de fármacos. A mudança de coloração exibida pela doxorrubicina como função do pH, ou até mesmo quando possivelmente adsorvida na MOF, motivou a realização do presente trabalho, o qual consiste na busca dos possíveis fatores que culminam na mudança de coloração apresentada pela DOX. Diante isso, cálculos envolvendo a reatividade, assim como, a espectroscopia UV/Vis das possíveis espécies tautoméricas da doxorrubicina foram realizados. Para tanto, foram aplicados os métodos semiempíricos, AM1, PM3, PM6 e RM1, e também DFT. Para realização dos cálculos espectroscópicos das geometrias no estado fundamental dos diferentes tautômeros da doxorrubicina, foi utilizado o método INDO/S-CIS. Para as espécies protonadas, todos os cálculos revelaram a DOX1 como sendo a espécie tautomérica mais estável e a DOX2 como sendo a mais instável. O método PM6 foi o método que se mostrou mais similar ao DFT, comparando os espectros de absorção da DOX1, assim como as estabilidades relativas entre os tautômeros. As energias relativas entre os tautômeros desprotonados calculadas pelos diferentes métodos aplicados foram menores para os protonados, pois os tautômeros desprotonados denotam maiores similaridades estruturais entre si. O estudo de reatividade mostrou que os métodos PM3 e AM1 apresentam o mesmo comportamento qualitativo quanto à predição da estrutura do estado de transição envolvido em cada reação de transferência de próton em fase gasosa. O método PM6 assemelhou-se mais ao RM1, divergindo apenas na conversão DOX1 → DOX4. Cada espectro de absorção calculado a partir das geometrias otimizadas com o método DFT para as diferentes espécies tautoméricas apresentou simplesmente uma banda na região de comprimentos de onda maiores (por volta de 400 nm), as quais equivalem à região do visível. Diferentemente, o espectro de absorção obtido experimentalmente em meio ácido apresentou três bandas na região compreendida entre 400 nm a 650 nm, dessa forma não se pode atribuir a predominância de um único tautômero no sistema, mas sim, a contribuição simultânea de todos os tautômeros. O estudo espectroscópico dos tautômeros desprotonados visando simular o efeito do pH básico sugere a presença, também, dos quatro tautômeros desprotonados no sistema, explicando dessa forma o aparecimento das várias bandas de absorção. A atipicidade apresentada pelo espectro obtido a pH 7 pode ser explicado a partir da presença tanto de espécies de doxorrubicina protonadas como desprotonadas. Dessa forma, a aplicação das ferramentas computacionais mostrou-se capaz de elucidar alguns eventos associados a espectroscopia e a reatividade da doxorrubicina.application/pdfporTautomerismoAnálise espectralQuímica computacionalIsomerismo dinâmicoDoxorrubicinaChemistrySpectrum analysisTautomerismCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAUm estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividadeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Químicainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSTEXTEDVONALDO_FLORENCIO_SILVA.pdf.txtEDVONALDO_FLORENCIO_SILVA.pdf.txtExtracted texttext/plain101752https://ri.ufs.br/jspui/bitstream/riufs/6100/2/EDVONALDO_FLORENCIO_SILVA.pdf.txt299bdf21215ce3319c6d0c7713d7c2efMD52THUMBNAILEDVONALDO_FLORENCIO_SILVA.pdf.jpgEDVONALDO_FLORENCIO_SILVA.pdf.jpgGenerated Thumbnailimage/jpeg1340https://ri.ufs.br/jspui/bitstream/riufs/6100/3/EDVONALDO_FLORENCIO_SILVA.pdf.jpg9c3ce77faf999e58d129cc3f4f0612c8MD53ORIGINALEDVONALDO_FLORENCIO_SILVA.pdfEDVONALDO_FLORENCIO_SILVA.pdfapplication/pdf1747232https://ri.ufs.br/jspui/bitstream/riufs/6100/1/EDVONALDO_FLORENCIO_SILVA.pdfeb246a38932dce95eb2a587f26a22888MD51riufs/61002019-05-17 18:00:22.855oai:ufs.br:riufs/6100Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2019-05-17T21:00:22Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.por.fl_str_mv |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
title |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
spellingShingle |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade Florêncio e Silva, Edvonaldo Tautomerismo Análise espectral Química computacional Isomerismo dinâmico Doxorrubicina Chemistry Spectrum analysis Tautomerism CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
title_full |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
title_fullStr |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
title_full_unstemmed |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
title_sort |
Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade |
author |
Florêncio e Silva, Edvonaldo |
author_facet |
Florêncio e Silva, Edvonaldo |
author_role |
author |
dc.contributor.author.fl_str_mv |
Florêncio e Silva, Edvonaldo |
dc.contributor.advisor1.fl_str_mv |
Costa Júnior, Nivan Bezerra da |
contributor_str_mv |
Costa Júnior, Nivan Bezerra da |
dc.subject.por.fl_str_mv |
Tautomerismo Análise espectral Química computacional Isomerismo dinâmico Doxorrubicina |
topic |
Tautomerismo Análise espectral Química computacional Isomerismo dinâmico Doxorrubicina Chemistry Spectrum analysis Tautomerism CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Chemistry Spectrum analysis Tautomerism |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
The doxorubicin (DOX) assumes a prominent position among the drugs widely applied in treatment human cancer. This chemotherapeutic presents efficiency in the regression of various neoplasms, although adverse reactions may occur. As a result several strategies have been developed to reduce the adverse effects caused by the continued use of DOX. One of these strategy is the incorporation of doxorubicin into MOF (Metal Organic Framework), since these materials can act as excellent carriers of drugs. The color change exhibited by doxorubicin as a function of pH, or even possibly when adsorbed in MOF, motivated the present work. This work consists in finding the possible factors that culminate in color change presented by DOX. This way, calculations involving the reactivity, and the UV/Vis spectroscopy of the possible tautomeric species of doxorubicin were performed. Thus, we applied the semiempirical methods, AM1, PM3, PM6 and RM1, and also DFT. We used the method INDO/S-CIS to calculate the spectroscopic of ground state geometries of various tautomer. All calculations revealed DOX1 as the most stable and DOX2 as the most unstable for protonated species. The method PM6 method was the more similar to the DFT by comparing the absorption spectra of DOX1 as well as the relative stabilities of the tautomers. The relative energies between deprotonated tautomers calculated by applied methods were smaller than protonated species, because the deprotonated tautomers denote considerable structural similarities between them. The reactivity study showed that the methods AM1 andPM3 exhibit the same qualitative behavior about the prediction of the transition state structure involved in each proton transfer reaction in the gas phase. The method PM6 resembled more to RM1, being the only exception was the conversion DOX1 → DOX4. Each absorption spectrum calculated from the optimized geometries with the DFT method to the different tautomeric species showed simply a band in the region of longer wavelengths (around 400 nm), which correspond to the visible region. In contrast, the absorption spectra obtained experimentally in acidic showed three bands in the region between 400 to 650 nm, thus cannot be attributed to a single predominant tautomer system, but the simultaneous contributing of all tautomers. The spectroscopic study of deprotonated tautomers, in order to simulate the effect of basic pH, suggests the presence also of the four tautomers deprotonated in the system, thus explaining the appearance of several absorption bands. The spectrum obtained at pH 7 can be explained from the presence of both doxorubicin protonated as deprotonated species. Thus, the application of computational tools proved to be able to elucidate some events associated with spectroscopy and reactivity of doxorubicin. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-03-08 |
dc.date.accessioned.fl_str_mv |
2017-09-27T13:57:42Z |
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2017-09-27T13:57:42Z |
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