Associação de antibiótico com íons metálicos como estratégia de reposicionamento de fármacos: norfloxacina e ciprofloxacina combinada com íons Co2+ e Zn2+

Abstract

Eight compounds were obtained through hydrothermal synthesis in a Teflon-lined stainless steel reactor and were characterized by single-crystal and powder X-ray diffraction, thermal analysis, and infrared spectroscopy. Four of the structures obtained are identical, not novel, and belong to the category of metal-organic frameworks (MOFs), formed using the fluoroquinolone ciprofloxacin (CIPRO), starting from the metal salts Co(NO3)2·6H2O and Zn(NO3)2·6H2O, and the MOFs [M2+Glutamate)H2O·H2O]n (M2+= Co2+ or Zn2+). Two of the compounds are of the coordination complex type, formed from the reaction between the fluoroquinolone norfloxacin (NOR) and the metal nitrates Co2+and Zn2+.The cobalt complex [Co(NOR)2(H2O)2](NO3)2 is a novel compound, with a crystal structure belonging to space group P-1, and unit cell parameters a = 8.8090(3); b = 8.9412(3); c = 12.7041(4); α = 69.858(3); β = 72.567(3); γ = 70.258(3). The other two obtained compounds are novel structures of coordination polymers with molecular formulas [Co(NOR)2]n and [Zn(NOR)2·6H2O]n, originating from the reaction of norfloxacin with the MOFs [M2+(Glutamate)H2O·H2O]n. These structures belong to space group P2/n, with unit cell parameters for [Co(NOR)2]n being a = 10.7863(12); b = 11.4947(9); c = 13.7355(15); α = 90; β = 96.207(10) and γ = 90, while for [Zn(NOR)2·6H2O]n they are a = 10.39381(17); b = 22.8722(4); c = 14.4048(3); α = 90; β = 94.7703(16); γ = 90. In the novel complex, NOR acts as a bidentate deprotonated ligand, coordinating to the metal through quinolone oxygen atoms and one carboxylate. In the coordination polymers, NOR acts not only as a bidentate ligand via the quinolone oxygen and one carboxylate but also as a unidentate ligand through the terminal nitrogen in the piperazine ring, similar to the coordination polymers with CIPRO. All structures are hexacoordinate and exhibit slightly distorted octahedral geometry. The microbiological activity of the compounds was tested using three microorganisms: a gram- positive bacterium, Staphylococcus aureus; a gram-negative bacterium, Escherichia coli; and a fungus, Candida albicans. None of the compounds showed significant inhibition of fungal growth, whereas all of the synthesized compounds exhibited antibacterial activity against Escherichia coli, with a concentration range of 256 – 0.5 µg/mL. A toxicity test was conducted using the common fruit fly, Drosophila melanogaster, where all compounds demonstrated no toxicity even at a concentration of 3000 ppm.