Um estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade

• Ano de defesa: 2013
• Autor(a) principal: Florêncio e Silva, Edvonaldo
• Orientador(a): Costa Júnior, Nivan Bezerra da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Química
• Palavras-chave em Português: Tautomerismo; Análise espectral; Química computacional; Isomerismo dinâmico; Doxorrubicina
• Palavras-chave em Inglês: Chemistry; Spectrum analysis; Tautomerism
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://ri.ufs.br/handle/riufs/6100

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.