Estudo da interação do As(III) com modelo "zinc finger" da proteína NCp7 HIV-1 e complexos de Bi(III) e Sb(III) com ligantes contendo 2-mercapto-imidazol

Abstract

The ejection of zinc from its coordination site in Zn-finger protein can be promoted by other metal species through competitive binding. This is considered as a promising strategy to inactivate the Zn-finger protein and for the design of new and more efficient drugs. A study of the As(III) interaction with the CCHC zinc finger domain of the NCp7 protein of HIV-1 has been carried out using the fluorescence and circular dichroism spectroscopies. This study allowed a better understanding of the ability of As(III) to promote Zn ejection and brought new insights into the role of glutathione as a biomolecule that can facilitate the ejection of Zn. The exactly mechanism is not yet known, but the fluorescence and circular dichroism data shows the importance of the participation of glutathione in the system formed. The competition between As(III) and Zn(II) was evaluated in phosphate buffers of different pHs. Sb(III) and Bi(III) compounds with 2-mercapto-imidazole- and -mercapto-benzimidazole-type ligands have been synthesized. These complexes involve coordination of the metal specie with the S-atom from thiol group and the N-atom from imidazole, just like occurs in the zinc finger domains. Five new complexes, SbCl(Bzmiz)2.CH3OH, BiCl(Bzmiz).CH3OH, BiCl2(Bzmiz).2H2O, SbCl2(Miz) and BiCl2(Miz) were successfully obtained. Physico-chemical characterization was performed using NMR, FTIR and UV-vis spectroscopies, elementar analyses, conductimetric analyses and thermogravimetric analyses. Four crystals were also obtained from these complexes, except for the SbCl2(Miz) complex. X-Ray diffraction analyses of these crystals are in course.