Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/6437 |
Resumo: | The synthesis of transition metal compounds mainly with ruthenium, has been increasing along the time, since compounds of this kind have many applications in the biological fields, among them, as anticancer agent. In this work were synthesized and characterized ruthenium compounds with amino acids of the general formula [Ru(AA)(dppb)(bipy)]PF6, AA = amino acid, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2, 2`-bipyridine, using as precursor the cis-[RuCl2(dppb)(bipy)]. Standard techniques were used for characterization of the complexes, among them: 31P{1H} NMR and 13C, IR, UVVis, Cyclic Voltammetry, Differential Pulse Voltammetry and X-Ray diffraction. Also, were made cytotoxicity experiments in cells of the type MDA-MB-231 to evaluate the citotoxity of the complexes. In the 31P{1H} NMR spectra of the complexes four doublets were detected with values close to 46, 44, 39 e 38 ppm with exception of the compound [Ru(Gly)(dppb)(bipy)]PF6 that presented only two doublets on 45,3 and 38,5 ppm. This suggests that there is a mixture of diastereoisomers for all compounds, with exception for the complex [Ru(Gly)(dppb)(bipy)]PF6. At the cyclic voltammetry of all compounds, except of compound [Ru(L-Met)(dppb)(bipy)]PF6 (irreversible) is observed a quasi-reversible Ru(III)/Ru(II) redox process with values close to 1100 mV. Also, there is another process of lower intensity above 1200 mV that is better observed by this differential pulse voltammetry that are attributed to redox process of the amino acids. The electronic spectra of the compounds are practically the same, showing bands around 290, 420 and 500 nm (shoulder) that are attributed to intra-ligand π→π* or to dπ(Ru)→π*(bipy) transitions. The diastereoisomers of the compound [Ru(L-Ser)(dppb)(bipy)]PF6 were separated by HPLC. These diastereoisomers were identified by circular dichroism spectroscopy (CD). Crystals of the compounds [Ru(Gly)(dppb)(bipy)]PF6 and [Ru(L-Leu)(dppb)(bipy)]PF6, were obtained and both showed the nitrogen of the amino acid to be trans to the phosphorus atom of the dppb and the oxygen opposite to the nitrogen of the bipyridine. The IC50 of all compounds in the cellular experiments with tumoral lineage were found to be lower than that one of the cisplatin, especially the IC50 of the compound [Ru(L-Met)(dppb)(bipy)]PF6 (5 μM), which is 17,5 time lower than the IC50 of the cisplatin in the same experimental condition. |
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Almeida, Marcio Aurélio PinheiroBatista, Alzir Azevedohttp://lattes.cnpq.br/6469642481998660http://lattes.cnpq.br/28809678768236022016-06-02T20:36:20Z2009-10-142016-06-02T20:36:20Z2009-06-17ALMEIDA, Marcio Aurélio Pinheiro. Ruthenium complexes containing amino, acids with cytotoxic proprieties in tumour cells. 2009. 151 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2009.https://repositorio.ufscar.br/handle/ufscar/6437The synthesis of transition metal compounds mainly with ruthenium, has been increasing along the time, since compounds of this kind have many applications in the biological fields, among them, as anticancer agent. In this work were synthesized and characterized ruthenium compounds with amino acids of the general formula [Ru(AA)(dppb)(bipy)]PF6, AA = amino acid, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2, 2`-bipyridine, using as precursor the cis-[RuCl2(dppb)(bipy)]. Standard techniques were used for characterization of the complexes, among them: 31P{1H} NMR and 13C, IR, UVVis, Cyclic Voltammetry, Differential Pulse Voltammetry and X-Ray diffraction. Also, were made cytotoxicity experiments in cells of the type MDA-MB-231 to evaluate the citotoxity of the complexes. In the 31P{1H} NMR spectra of the complexes four doublets were detected with values close to 46, 44, 39 e 38 ppm with exception of the compound [Ru(Gly)(dppb)(bipy)]PF6 that presented only two doublets on 45,3 and 38,5 ppm. This suggests that there is a mixture of diastereoisomers for all compounds, with exception for the complex [Ru(Gly)(dppb)(bipy)]PF6. At the cyclic voltammetry of all compounds, except of compound [Ru(L-Met)(dppb)(bipy)]PF6 (irreversible) is observed a quasi-reversible Ru(III)/Ru(II) redox process with values close to 1100 mV. Also, there is another process of lower intensity above 1200 mV that is better observed by this differential pulse voltammetry that are attributed to redox process of the amino acids. The electronic spectra of the compounds are practically the same, showing bands around 290, 420 and 500 nm (shoulder) that are attributed to intra-ligand π→π* or to dπ(Ru)→π*(bipy) transitions. The diastereoisomers of the compound [Ru(L-Ser)(dppb)(bipy)]PF6 were separated by HPLC. These diastereoisomers were identified by circular dichroism spectroscopy (CD). Crystals of the compounds [Ru(Gly)(dppb)(bipy)]PF6 and [Ru(L-Leu)(dppb)(bipy)]PF6, were obtained and both showed the nitrogen of the amino acid to be trans to the phosphorus atom of the dppb and the oxygen opposite to the nitrogen of the bipyridine. The IC50 of all compounds in the cellular experiments with tumoral lineage were found to be lower than that one of the cisplatin, especially the IC50 of the compound [Ru(L-Met)(dppb)(bipy)]PF6 (5 μM), which is 17,5 time lower than the IC50 of the cisplatin in the same experimental condition.Síntese de compostos de metais de transição, principalmente com o rutênio vem aumentando ao longo dos anos, pois compostos desse tipo possuem diversas aplicações no campo da biologia, dentre elas como agentes antitumorais. Neste trabalho foram sintetizados compostos de rutênio com aminoácidos de formula geral [Ru(AA)(dppb)(bipy)]PF6, onde , AA = aminoácido, dppb = 1,4-bis(difenilfosfino)butano e bipy = 2, 2`-bipiridina, usando como precursor o cis-[RuCl2(dppb)(bipy)]. Foram utilizadas as técnicas usuais de caracterização dentre elas; RMN de 31P{1H} e 13C, UV-Vis, IV, Voltametria Cíclica e Analise Elementar. Também, foram feitos ensaios em linhagem de células do tipo MDA-MB-231(câncer de mama) com a intenção de avaliar as células tumorais dos complexos in vitro. Nos espectros de RMN de 31P{1H} dos complexos foram observados quatro dubletos com valores próximos de 46, 44, 39 e 38 ppm para todos os compostos sintetizados com exceção ao composto [Ru(Gly)(dppb)(bipy)]PF6 que apresenta somente dois dubletos em 45,3 e 38,5 ppm. Isto sugere que há uma mistura de diastereoisômeros para todos os compostos, menos para o complexo [Ru(Gly)(dppb)(bipy)]PF6. Para a voltametria cíclica de todos os compostos exceto o composto [Ru(L-Met)(dppb)(bipy)]PF6 é observado um processo de redox Ru(II)/Ru(III) quasi-reversivel em valores próximos de 1100 mV. Também existe outro processo de menor intensidade acima de 1200 mV, que é melhor observado pela voltametria de pulso diferencial, o qual é atribuído a processo redox dos aminoácidos. Os espectros eletrônicos dos compostos com aminoácidos são todos similares, apresentam bandas em 290, 420 e 500 nm (ombro) que são atribuídas a transições intraligante π π* e dπ(Ru)→π*(bipy), sucessivamente. Os diastereoisômeros do composto [Ru(L-Ser)(dppb)(bipy)]PF6 foram separados por CLAE. Estes diastereoisomeros foram identificados por espectroscopia de dicroísmo circular(DC). Foram obtidos cristais do composto [Ru(Gly)(dppb)(bipy)]PF6 e [Ru(L-Leu)(dppb)(bipy)]PF6, em ambos o nitrogênio do aminoácido encontra-se trans ao átomo de fósforo da dppb e o oxigênio trans ao átomo de nitrogênio da bipiridina. Nos testes biológicos os resultados foram bastante promissores. Os IC50 nos ensaios celulares com linhagem tumoral para todos os compostos foram muito abaixo do valor da cisplatina, dando destaque para o complexo [Ru(L-Met)(dppb)(bipy)]PF6 com um valor de 5 μmol.L-1, valor este 17,5 vezes menor que o do cisplatina nas mesmas condições experimentais.Fundação de Amparo a Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhãoapplication/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarBRQuímica inorgânicaComplexos de rutênioAminoácidosBifosfinaCIENCIAS EXATAS E DA TERRA::QUIMICAComplexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumoraisRuthenium complexes containing amino, acids with cytotoxic proprieties in tumour cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL2556.pdfapplication/pdf3791891https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/6437/1/2556.pdfc6b0d24e70c61a5625a73dcb78ad5a34MD51THUMBNAIL2556.pdf.jpg2556.pdf.jpgIM Thumbnailimage/jpeg8119https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/6437/2/2556.pdf.jpg30fa922b6c4e2d348f704ad389989926MD52ufscar/64372019-09-11 02:57:20.11oai:repositorio.ufscar.br:ufscar/6437Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222019-09-11T02:57:20Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
dc.title.alternative.eng.fl_str_mv |
Ruthenium complexes containing amino, acids with cytotoxic proprieties in tumour cells |
title |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
spellingShingle |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais Almeida, Marcio Aurélio Pinheiro Química inorgânica Complexos de rutênio Aminoácidos Bifosfina CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
title_full |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
title_fullStr |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
title_full_unstemmed |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
title_sort |
Complexos de rutênio contendo aminoácidos, com propriedades citotóxicas em células tumorais |
author |
Almeida, Marcio Aurélio Pinheiro |
author_facet |
Almeida, Marcio Aurélio Pinheiro |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/2880967876823602 |
dc.contributor.author.fl_str_mv |
Almeida, Marcio Aurélio Pinheiro |
dc.contributor.advisor1.fl_str_mv |
Batista, Alzir Azevedo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6469642481998660 |
contributor_str_mv |
Batista, Alzir Azevedo |
dc.subject.por.fl_str_mv |
Química inorgânica Complexos de rutênio Aminoácidos Bifosfina |
topic |
Química inorgânica Complexos de rutênio Aminoácidos Bifosfina CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
The synthesis of transition metal compounds mainly with ruthenium, has been increasing along the time, since compounds of this kind have many applications in the biological fields, among them, as anticancer agent. In this work were synthesized and characterized ruthenium compounds with amino acids of the general formula [Ru(AA)(dppb)(bipy)]PF6, AA = amino acid, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2, 2`-bipyridine, using as precursor the cis-[RuCl2(dppb)(bipy)]. Standard techniques were used for characterization of the complexes, among them: 31P{1H} NMR and 13C, IR, UVVis, Cyclic Voltammetry, Differential Pulse Voltammetry and X-Ray diffraction. Also, were made cytotoxicity experiments in cells of the type MDA-MB-231 to evaluate the citotoxity of the complexes. In the 31P{1H} NMR spectra of the complexes four doublets were detected with values close to 46, 44, 39 e 38 ppm with exception of the compound [Ru(Gly)(dppb)(bipy)]PF6 that presented only two doublets on 45,3 and 38,5 ppm. This suggests that there is a mixture of diastereoisomers for all compounds, with exception for the complex [Ru(Gly)(dppb)(bipy)]PF6. At the cyclic voltammetry of all compounds, except of compound [Ru(L-Met)(dppb)(bipy)]PF6 (irreversible) is observed a quasi-reversible Ru(III)/Ru(II) redox process with values close to 1100 mV. Also, there is another process of lower intensity above 1200 mV that is better observed by this differential pulse voltammetry that are attributed to redox process of the amino acids. The electronic spectra of the compounds are practically the same, showing bands around 290, 420 and 500 nm (shoulder) that are attributed to intra-ligand π→π* or to dπ(Ru)→π*(bipy) transitions. The diastereoisomers of the compound [Ru(L-Ser)(dppb)(bipy)]PF6 were separated by HPLC. These diastereoisomers were identified by circular dichroism spectroscopy (CD). Crystals of the compounds [Ru(Gly)(dppb)(bipy)]PF6 and [Ru(L-Leu)(dppb)(bipy)]PF6, were obtained and both showed the nitrogen of the amino acid to be trans to the phosphorus atom of the dppb and the oxygen opposite to the nitrogen of the bipyridine. The IC50 of all compounds in the cellular experiments with tumoral lineage were found to be lower than that one of the cisplatin, especially the IC50 of the compound [Ru(L-Met)(dppb)(bipy)]PF6 (5 μM), which is 17,5 time lower than the IC50 of the cisplatin in the same experimental condition. |
publishDate |
2009 |
dc.date.available.fl_str_mv |
2009-10-14 2016-06-02T20:36:20Z |
dc.date.issued.fl_str_mv |
2009-06-17 |
dc.date.accessioned.fl_str_mv |
2016-06-02T20:36:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ALMEIDA, Marcio Aurélio Pinheiro. Ruthenium complexes containing amino, acids with cytotoxic proprieties in tumour cells. 2009. 151 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2009. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/6437 |
identifier_str_mv |
ALMEIDA, Marcio Aurélio Pinheiro. Ruthenium complexes containing amino, acids with cytotoxic proprieties in tumour cells. 2009. 151 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2009. |
url |
https://repositorio.ufscar.br/handle/ufscar/6437 |
dc.language.iso.fl_str_mv |
por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de São Carlos |
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Programa de Pós-Graduação em Química - PPGQ |
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UFSCar |
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BR |
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Universidade Federal de São Carlos |
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