Estudos de Filmes de Langmuir e LB de complexo fosfínico de rutênio visando potenciais aplicações biológicas

• Ano de defesa: 2014
• Autor(a) principal: Sandrino, Bianca
• Orientador(a): Wohnrath, Karen
• Banca de defesa: Tominaga, Tania Toyomi , Fujiwara, Sérgio Toshio , Caetano, Wilker , Nascimento, Fábio B. do
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: UNIVERSIDADE ESTADUAL DE PONTA GROSSA
• Programa de Pós-Graduação: Programa Associado de Pós-Graduação em Química - Doutorado
• Departamento: Físico Química, Química Analitica, Química Organica, Química Inorgânica
• País: BR
• Palavras-chave em Português: complexo de rutênio; anticancerígenos; fosfolipídios; filmes de Langmuir
• Palavras-chave em Inglês: ruthenium complex; anticancer; phospholipids; langmuir films
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA INORGANICA
• Link de acesso: http://tede2.uepg.br/jspui/handle/prefix/5

One of the major challenges in drug design is to identify compounds with potential toxicity toward target cells, preferably with molecular-level understanding of their mode of action. In this study, the antitumor property of a ruthenium complex, mer-RuCl3(dppb)(VPy)] (dppb = 1,4-bis (diphenylphosphine) butane and VPy = 4-vinylpyridine),RuVPy) was analyzed. Results showed that this compound led to a mortality rate of 50% of human laryngeal carcinoma HEp-2 cell with 120 ±10 mol L-1, indicating its high toxicity. Toward a better understanding if its mode of action is associated with its interaction with cell membranes, Langmuir monolayers were used as a membrane model. RuVPy had a strong effect on the surface pressure isotherms, especially on the elastic properties of the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) and dipalmitoylphosphatidylserine (DPPS) phospholipids. Results of thermodynamic parameters indicated miscibility between the components is not ideal mixed monolayers. Preferably attractive and repulsive interactions between RuVPy and zwitterionic or anionic phospholipids, respectively, are observed with mixed monolayer of DPPS/RuVPy energetically unfavorable. These data were confirmed polarization - modulated infrared reflection-absorption spectroscopy (PM-IRRAS). In addition, interactions between the positive group from RuVPy and the phosphate group from phospholipids were corroborated by density functional theory (DFT) calculations, allowing the determination of the Ru complex orientation at the air-water interface. Proof of interaction was confirmed by electrochemical results of Langmuir-Blodgett films of the phospholipid/RuVPy mixture. The presence of the RuVPy on the conductor substrate, which presents higher electron density, form "defects" in the monolayer of phospholipids increasing accumulation of electrons in the electrode/solution interface making it more permeable material. Although possible contributions from receptors or other cell components cannot be discarded, the results reported here represent evidence for significant effects on the cell membranes which are probably associated with the high toxicity of RuVPy.