Banca de DEFESA: ESTHER SARAIVA AREAS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : ESTHER SARAIVA AREAS
DATA : 01/02/2018
HORA: 14:00
LOCAL: UFRRJ - Sala 50
TÍTULO:

Synthesis of novel cobalt complexes containing coumarin-b-ketoester hybrid: investigation of the cytotoxicity and reactivity in solution

PALAVRAS-CHAVES:

 Cobalt complexes, coumarins, bioreductive prodrugs.

PÁGINAS: 80
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
RESUMO:

In this work it was synthesized novel cobalt complexes containing a fluorescent hybrid ligand of coumarin-b-ketoester (HL) of the type [Co(L)(Am)](ClO₄)_n, where L is a coumarin derivative in its anionic form and Am is the auxiliary amine: TPA (for 1b-Co^II and 2b-Co^III) or Py₂en (for 2c-Co^III). The synthetic procedure to obtain 1b led to the formation of the Co^II specie (1b-Co^II), which was confirmed by CHN elemental analysis, molar conductivity and X-ray diffraction (XRD). The 1b-Co^II ion complex is a cationic hexacoordinated specie, containing the coumarin in the L^1- form, acting as O,O-donor, and a neutral TPA as N,N',N',N'-donor. XRD results obtained for HL and 1b-Co^II showed that the complexation led to the increase of ligand planarity. For 2b-Co^III, the use of [Co^III(TPA)Cl₂]ClO₄ as a starting material led to the formation of the Co^III complex, however, CHN elemental analysis and ¹H NMR also indicated the presence of the precursors in the isolated solid. The complex 2c-Co^III was obtained from the same methodology used for 1b-Co^II, however, the presence of a more basic amine (Py₂en) favored the Co^III specie. Elemental analysis, molar conductivity, infrared and ¹H NMR spectroscopy data indicated a structure of the type [Co^III(L)(Py₂en)](ClO₄)₂, where L^1- also interacts with the metal through the carbonyl groups of the b-ketoester moiety. DFT calculations showed that the band at 448 nm in the UV-Vis spectra of 1b-Co^II, obtained in buffer solution (pH 7,4), refers to the p-p* transition centered on L^1-, and for 2c-Co^III the band at 455 nm is related to a mixture of p-p* and LMCT transitions. Cyclic voltammetry showed that the complexes exhibit a quasi-reversible process associated with the Co^III/Co^II pair, with E_pc in the order 2c-Co^III < 1b-Co^II < 2b-Co^III, which was associated to the electronic properties of the auxiliary amine. The higher p-acceptor character of the TPA facilitates the electron gain by the cobalt in 1b-Co^II and 2b-Co^III, while Py₂en, which has a larger s-donor character, leads to a lower potential for 2c-Co^III. HL exhibits a cathodic process associated to the reduction of the carbonyl groups, which did not shift after coordination. Reactivity assays of 2c-Co^III in buffer solution (pH 7,4) monitored by fluorescence spectroscopy indicated that the ligand was released in the presence of a reducing agent (sodium ascorbate) for 8.5 h, which was most pronounced in argon atmosphere, suggesting that dissociation of L^1- occurs preferentially after reduction of the metal. 2c-Co^III was stable in buffer solution without reducing agent. The cytotoxicity investigation of HL, 1b-Co^II and 2c-Co^III against B16-F10 (metastatic murine melanoma), 4T1 (murine mammary melanoma) and BHK-21 (non-tumor cell of hamster kidney) showed that the free ligand was not active, but the coordination favored its cytotoxicity in most cases. 2c-Co^III exhibited the best overall activity when compared to 1b-Co^II, presenting selective cytotoxicity to cancer cells (45.9 ± 5.2 mM e 39.1 ± 6.6 mM para B16-F10 e 4T1, respectively) and being inactive against normal cells (71.2 ± 6.2 mM).

MEMBROS DA BANCA:
Presidente - 1579187 - AMANDA PORTO NEVES
Interno - 1475121 - MARCELO HAWRYLAK HERBST
Externo à Instituição - MAURÍCIO LANZNASTER - UFF