RESUMEN
As green solvents ionic liquids (ILs) show high potential in nuclear industry for extraction and purification of actinides. However, to date relatively little information has been gained on ILs application in microbial processes, for example biosorption of radionuclides. We investigated the effects of three ILs, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), N-ethylpyridinium trifluoroacetate (EtPyCF3COO) and N-ethylpyridinium tetrafluoroborate (EtPyBF4) on the growth and biosorption of uranium by Clostridium sp. The ILs affected the growth of the bacterium as evidenced by decreases in optical density, total gas production, and organic acids production from glucose metabolism. The IC50-48h of three ILs decreased in the order of BMIMPF6 (8.26mM)>EtPyBF4 (7.04mM)>EtPyCF3COO (4.05mM). Uranium biosorption by the bacterial cells decreased by 75% in the presence of 1% (v/v) BMIMPF6 and by about 90% with 1% (v/v) EtPyBF4 or EtPyCF3COO, in comparison to the control without ILs. The diminished biosorption may be attributed to the membrane damages induced by EtPyBF4 and EtPyCF3COO, which can be visualized by Transmission Electron Microscope (TEM) analysis. Energy-dispersive X-ray spectroscopy (EDS) analysis revealed the accumulation of uranium inside peripheral membrane of the cells exposed to uranium alone or with BMIMPF6, while little or no accumulation was observed in the presence of EtPyBF4 and EtPyCF3COO. These results imply that potential toxicity of ILs towards microorganisms is a particularly important issue in limiting its biotechnological applications.
Asunto(s)
Clostridium/efectos de los fármacos , Líquidos Iónicos/toxicidad , Uranio/metabolismo , Absorción , Clostridium/metabolismo , Microscopía Electrónica de Transmisión , Espectrometría por Rayos XRESUMEN
The ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], N-ethylpyridiniumtrifluoroacetate [EtPy][CF3COO] and N-ethylpyridiniumtetrafluoroborate [EtPy][BF4], affected the reduction and precipitation of uranium by Clostridium sp. to a varying degree. Characterization of uranium association with the ionic liquids showed that uranium formed a monodentate complex with the anion BF4(-) and PF6(-) of [EtPy][BF4] and [BMIM][PF6], respectively; and a bidentate complex with carboxylate of [EtPy][CF3COO]. Bioreduction of U(VI) was influenced by the type of complex formed: monodentate complexes were readily reduced whereas the bidentate complex of U(VI) with [CF3COO] was recalcitrant. [EtPy][BF4] affected the rate and extent of precipitation of the reduced uranium; at higher concentration the reduced U(IV) remained in the solution phase. The results suggest that by tuning the properties of ionic liquids they may be valuable candidates for uranium biotreatment.
Asunto(s)
Precipitación Química , Clostridium/metabolismo , Líquidos Iónicos/farmacología , Uranio/metabolismo , Contaminantes Radiactivos del Agua/metabolismo , Biodegradación Ambiental/efectos de los fármacos , Clostridium/efectos de los fármacos , Imidazoles/farmacología , Cinética , Compuestos de Piridinio/farmacología , Soluciones , Uranio/aislamiento & purificación , Contaminantes Radiactivos del Agua/aislamiento & purificación , Espectroscopía de Absorción de Rayos XRESUMEN
Podophyllotoxin (1) has been known to possess anti-tumor activity and is still considered an important lead for research and development of antineoplastic agents. Derivatives of podophyllotoxin, namely etoposide (2), etopophos (3) and teniposide (4) have been developed and are currently used in clinic for the treatment of a variety of malignancies. These agents are also used in combination therapies with other drugs. Due to the drug resistance developed by cancer cells as well as side effects associated with the use of these agents in clinic, the search for new effective anticancer analogues of podophyllotoxin remains an intense area of research. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. These issues provide strong impetus to a search for analogues of 1 with simplified structures, which can be accessible via short synthetic sequences from simple starting materials. Even if such initial compounds might have diminished cytotoxic potencies compared with the parent cyclolignan, the ease of preparation of carefully designed libraries of analogues would lead to more informative SAR studies and expeditious structure optimization. In this regard, during the last two decades considerable efforts have been made to synthesize aza- analogs of podophyllotoxin, i. e. aza-podophyllotoxins, with hetero atoms at different positions of the podophyllotoxin skeleton, while keeping the basic podophyllotoxin structure. Recently, there have been significant efforts towards the convenient synthesis of aza-analogs of 1. The use of multicomponent reactions (MCRs) and the synergies of ultrasound and microwave irradiations have increased the synthetic speed and variety of azapodophyllotoxins which are and will be available to be tested against a diverse population of carcinomas and other diseases. It has been reported that several aza-podophyllotoxins retain a great fraction of the cytotoxicity associated with the parent lignan. This review focuses on the strategies towards synthesis of various aza-podophyllotoxin analogues and their biological activities.
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Técnicas de Química Sintética/métodos , Podofilotoxina/síntesis química , Podofilotoxina/farmacología , Podophyllum/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Podofilotoxina/química , Podofilotoxina/uso terapéuticoRESUMEN
We examined the effects of the ionic liquids (ILs), 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], N-ethylpyridinium tetrafluoroborate [EtPy][BF4], and N-ethylpyridinium trifluoroacetate [EtPy][CF3COO] on Pseudomonas fluorescens, a ubiquitous soil bacterium. In the presence of 0.5- and 1% of [BMIM][PF6] or [EtPy][CF3COO] the growth of bacteria was inhibited, whereas exposing them to 1% [EtPy][BF4] increased the lag period wherein bacteria adapt to growth conditions before continuing to grow. However, at higher concentrations (5% and 10%), no growth was observed. The inhibitory effects were evident by a decrease in the optical density of the culture, a decline in the consumption of the carbon source, citric acid, and a change in the size of the bacterium. At concentrations below 1%, [EtPy][BF4] was metabolized by P. fluorescens in the presence of citric acid. Oxidation of the side alkyl-chain of [EtPy][BF4] caused the accumulation of N-hydroxylethylpyridinium and pyridinium as major degradation products.
Asunto(s)
Imidazoles/toxicidad , Líquidos Iónicos/toxicidad , Pseudomonas fluorescens/efectos de los fármacos , Compuestos de Piridinio/toxicidad , Biodegradación Ambiental , Ácido Cítrico/metabolismo , Concentración de Iones de Hidrógeno , Imidazoles/metabolismo , Líquidos Iónicos/metabolismo , Pseudomonas fluorescens/crecimiento & desarrollo , Pseudomonas fluorescens/metabolismo , Compuestos de Piridinio/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidadRESUMEN
Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic resolution of methyl-4-(tert-butyroxycarbonyl)-piperazine-2-carboxylate using a low cost enzyme alcalase.