Estudo espectroscópico da interação entre as proteínas séricas humanas Albumina e transferrina com o potencial agente quimioterapêutico cloreto de cis-tetraminodiclorutênio (III)

• Ano de defesa: 2013
• Autor(a) principal: Guedes, Adriana Pereira Mundim
• Orientador(a): Lacerda, Elisângela de Paula Silveira
• Banca de defesa: Lacerda, Elisângela de Paula Silveira, Batista, Alzir Azevedo, Santana, Ricardo Costa de, Vieira, Ernanni Damião
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Ciências Farmacêuticas (FF)
• Departamento: Faculdade Farmácia - FF (RG)
• País: Brasil
• Palavras-chave em Português: Complexos de rutênio (III); Proteínas séricas; Interação; UV-vis; Espectroscopia de fluorescência; Ressonância paramagnética eletrônica (RPE)
• Palavras-chave em Inglês: Ru(III) complex; Serum proteins; Interaction; UV-vis; Fluorescence spectroscopy; Electron paramagnetic resonance spectroscopy (EPR)
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/3363

Motivated by the perspective of ruthenium complexes to be used in cancer treatment, our research group has tested the hipotesis that some complexes of Ru (III) are able to interact with serum proteins, particularly albumin and transferrin. The Complex cis- [RuCl2(NH3)4]Cl (CTRu(III)) have been tested against different kind of tumor cells, obtaining good results. Starting from promising results obtained with this compound, subsequent studies are required to understanding the mechanism by which it exerts specificity for tumor cells. In this article, we report the first application of absorption UV-Vis, Fluorescence and Electron Paramagnetic Resonance (EPR) spectroscopy, to study the complex CTRu(III) interaction with human serum albumin (hsA) and bovine serum albumin (bsA). Fluorescence measurements revealed strong proteinsbound complex with Ksv of 1.32 x 105 and 3.71 x 105 for hsA and bsA, respectively. EPR spectra from mono-nuclear Ru(III) complexes in buffer, showed a significant decrease in the overall signal intensity following the first aquation step, is consistent with the formation of oxo-bridged Ru(III) dimers. EPR spectra revealed that the BSA very rapid binding to the protein via covalent binding through ligand-exchange with protein side chains, likely with histidine imidazoles. On the other hand, the complex binds non-covalently in hsA, probably as a product of the oligomerization of the complex in hemin-biding pocket. Furthermore, two species are slowly formed by covalent binding of the complex with the histidine residues, producing a species of axial symmetry and the other rhombic symmetry. These bonds seem to arise from the interaction of the complex with the histidine residue located in the binding Sudlow’s site II.