This paper reports the synthesis of a series of new tetraethylammonium-based amino acid chiral ionic liquids (CILs). Their physico-chemical properties, including melting point, thermal stability, viscosity and ionic conductivity, have been comprehensively studied. The obtained results indicated that the decomposition for these salts proceeds in one step and the temperature of decomposition (T(onset)) is in the range of 168-210 degrees C. Several new CILs prepared in this work showed high ionic conductivity compared to the amino acid ionic liquids (AAILs) found in the literature.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 µM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs.
β-Cyclodextrin-ionic liquid polymer (CD-ILP) was first synthesized by functionalized β-cyclodextrin (CD) with 1-benzylimidazole (BIM) to form monofunctionalized CD (βCD-BIMOTs) and was further polymerized using a toluene diisocyanate (TDI) linker to form insoluble CD-ILP (βCD-BIMOTs-TDI). The βCD-BIMOTs-TDI polymer was characterized using various tools and the results obtained were compared with those derived from the native β-cyclodextrin polymer (βCD-TDI). The SEM result shows that the presence of ionic liquid (IL) increases the pore size, while the thermo gravimetric analysis (TGA) result shows that the presence of IL increases the stability of the polymer. Meanwhile, Brunauer-Emmett-Teller (BET) results show that βCD-BIMOTs-TDI polymer has 1.254 m(2)/g surface areas and the Barret-Joyner-Halenda (BJH) pore size distribution result reveals that the polymer exhibits macropores with a pore size of 77.66 nm. Preliminary sorption experiments were carried out and the βCD-BIMOTs-TDI polymer shows enhanced sorption capacity and high removal towards phenols and As(V).
The supramolecular structure of the inclusion complex of β-cyclodextrin (β-CD) with 1,1',2,2'-tetramethyl-3,3'-(p-phenylenedimethylene) diimidazolium dibromide (TetraPhimBr), a dicationic ionic liquid, has been investigated. The inclusion complex with 1:1 molar ratio was prepared by a kneading method. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) analysis, (1)H NMR and thermogravimetric analysis (TGA) confirmed the formation of the inclusion complex. The results showed that the host-guest system is a fine crystalline powder. The decomposition temperature of the inclusion complex is lower than that of its parent molecules, TetraPhimBr and β-CD individually.
Ionic liquid (IL) surfactants have attracted great interest as promising substitutes for conventional surfactants owing to their exceptional and favorable physico-chemical properties. However, most IL surfactants are not eco-friendly and form unstable micelles, even when using a high concentration of the surfactant. In this study, we prepared a series of halogen-free and biocompatible choline-fatty-acid-based ILs with different chain lengths and degrees of saturation, and we then investigated their micellar properties in aqueous solutions. Characterization of the synthesized surface-active ILs (SAILs) was performed by 1H and 13C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. The surface-active properties of the SAILs were investigated by tensiometry, conductometry, and dynamic light scattering measurements. The critical micelle concentration of the SAILs was found to be 2-4 times lower than those of conventional surfactants. The thermodynamic properties of micellization (ΔG0m, ΔH0m, and ΔS0m) indicate that the micellization process of the SAILs is spontaneous, stable, and entropy-driven at room temperature. The cytotoxicity of the SAILs was evaluated using mammalian cell line NIH 3T3. Importantly, [Cho][Ole] shows lower toxicity than the analogous ILs with conventional surfactants. These results clearly suggest that these environmentally friendly SAILs can be used as a potential alternative to conventional ILs for various purposes, including biological applications.
Three 1-(2-hydroxyethyl)-3-alkylimidazolium chloride room temperature ionic liquids (ILs) [2OHimC(n)][Cl]; (n=0, 1, 4) have been synthesized from the appropriate imidazole precursors and characterized by IR and NMR spectroscopies and elemental analysis. Their anti-microbial activities were investigated using the well-diffusion method. The viabilities of Escherichia coli, Aeromonas hydrophila, Listeria monocytogenes and Salmonella enterica as a function of IL concentrations were studied. The minimal inhibitory concentrations (MICs) and EC₅₀ values for the present ILs were within the concentration range from 60 to 125 mM and 23 to 73 mM. The anti-microbial potencies of the present ILs were compared to a standard antibiotic, gentamicin. The finding affords additional perspective on the level of ILs toxicity to aquatic lifeforms and yet, this characteristic can be readily harnessed to detect microbial growth and activity.
Phenolic acids of oak gall were extracted using ultrasonic-probe assisted extraction (UPAE) method in the presence of ionic liquid. It was compared with classical ultrasonic-bath assisted extraction (CUBAE) and conventional aqueous extraction (CAE) method, with and without the presence of ionic liquid. Remarkably, the UPAE method yielded two-fold higher extraction yield with the presence of ionic liquid, resulting 481.04 mg/g for gallic acids (GA) and 2287.90 mg/g for tannic acids (TA), while a decreased value of 130.36 mg/g for GA and 1556.26 mg/g for TA were resulted with the absence of ionic liquid. Intensification process resulted the highest yield of 497.34 mg/g and 2430.48 mg/g for GA and TA, respectively, extracted at temperature 50 °C with sonication intensity of 8.66 W/cm2 and 10% duty cycle, diluted in ionic liquid, 1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [Bmim][Tf2N] at concentration of 0.10 M with sample-to-solvent ratio 1:10 for 8 h. Peleg's model successfully predicted the UPAE process confirming that extraction capacity is the controlling factor in extracting phenolic acids. Hence, it can be concluded that UPAE method and ionic liquid have synergistic effect as it effectively enhanced the extraction efficiency to increase the bioactive constituents yield.
Over the past decades, Ionic liquids (ILs) have gained considerable attention from the scientific community in reason of their versatility and performance in many fields. However, they nowadays remain mainly for laboratory scale use. The main barrier hampering their use in a larger scale is their questionable ecological toxicity. This study investigated the effect of hydrophobic and hydrophilic cyclic cation-based ILs against four pathogenic bacteria that infect humans. For that, cations, either of aromatic character (imidazolium or pyridinium) or of non-aromatic nature, (pyrrolidinium or piperidinium), were selected with different alkyl chain lengths and combined with both hydrophilic and hydrophobic anionic moieties. The results clearly demonstrated that introducing of hydrophobic anion namely bis((trifluoromethyl)sulfonyl)amide, [NTF2] and the elongation of the cations substitutions dramatically affect ILs toxicity behaviour. The established toxicity data [50% effective concentration (EC50)] along with similar endpoint collected from previous work against Aeromonas hydrophila were combined to developed quantitative structure-activity relationship (QSAR) model for toxicity prediction. The model was developed and validated in the light of Organization for Economic Co-operation and Development (OECD) guidelines strategy, producing good correlation coefficient R2 of 0.904 and small mean square error (MSE) of 0.095. The reliability of the QSAR model was further determined using k-fold cross validation.
Selected Brønsted acidic ionic liquids were tested as homogeneous catalysts for the dehydration of methanol to dimethyl ether. Ionic liquids incorporating an alkanesulfonic acid as a part of the cation, a complex acidic anion, [A(2)H](-), or both, proved to be good catalysts for this process, providing high conversions and selectivities. Homogeneous catalysis in the liquid state represents a novel approach to dimethyl ether synthesis.
The partitioning of β-mannanase derived from Bacillus subtilis ATCC 11774 in aqueous two-phase system (ATPS) was studied. The ATPS containing different molecular weight of polyethylene glycol (PEG) and types of salt were employed in this study. The PEG/salt composition for the partitioning of β-mannanase was optimized using response surface methodology. The study demonstrated that ATPS consists of 25% (w/w) of PEG 6000 and 12.52% (w/w) of potassium citrate is the optimum composition for the purification of β-mannanase with a purification fold (PF) of 2.28 and partition coefficient (K) of 1.14. The study on influences of pH and crude loading showed that ATPS with pH 8.0 and 1.5% (w/w) of crude loading gave highest PF of 3.1. To enhance the partitioning of β-mannanase, four ionic liquids namely 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4), 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim]BF4), 1-butyl-3-methylimidazolium bromide ([Bmim]Br), 1-ethyl-3-methylimidazolium bromide ([Emim]Br) was added into the system as an adjuvant. The highest recovery yield (89.65%) was obtained with addition of 3% (w/w) of [Bmim]BF4. The SDS-PAGE analysis revealed that the β-mannanase was successfully recovered in the top phase of ATPS with the molecular size of 36.7kDa. Therefore, ATPS demonstrated a simple and efficient approach for recovery and purification of β-mannanase from fermentation broth in one single-step strategy.
The production of reducing sugars from sago waste via sequential ionic liquid dissolution-solid acid saccharification was optimized in this study. Ionic liquid dissolution of sago waste with 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) was conducted prior to the solid acid saccharification with Amberlyst 15 (A15). The effect of time, temperature and substrate loading during dissolution reaction; and the effect of time, temperature and catalyst loading during saccharification reaction were examined by applying central composite design (CCD) separately. Both dissolution and saccharification reactions were respectively modeled into quadratic polynomial equations with good predictive accuracies. A high reducing sugars yield of 98.3% was obtained under the optimized conditions, i.e. dissolution at 1.75h, 160°C, 1.5% substrate loading, and saccharification at 0.5h, 130°C, 4% catalyst loading. From comparison studies of different saccharification schemes, the sequential ionic liquid dissolution-solid acid saccharification has proven to be a potential method in reducing sugars production from the lignocellulosic biomass.
Ectoine is a zwitterionic amino acid derivative that can be naturally sourced from halophilic microorganisms. The increasing demands of ectoine in various industries have urged the researches on the cost-effective approaches on production of ectoine. Ionic liquids-based aqueous biphasic system (ILABS) was applied to recover Halomonas salina ectoine from cells hydrolysate. The 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4 was used in the ILABS and the recovery efficiency of ILABS to recover ectoine from H. salina cells lysate was evaluated by determining the effects of phase composition; pHs; crude loading and additional neutral salt (NaCl). The hydrophilic ectoine was targeted to partition to the hydrophilic salt-rich phase. A total yield (YB) of 96.32% ± 1.08 of ectoine was obtained with ILABS of phase composition of 20% (w/w) (Bmim)BF4 and 30% (w/w) sulfate salts; system pH of 5.5 when the 20% (w/w) of crude feedstock was applied to the ILABS. There was no significant enhancement on the ectoine recovery efficiency using the ILABS when NaCl was added, therefore the ILABS composition without the additional neutral salt was recommended for the primary purification of ectoine. Partition coefficient (KE) of 30.80 ± 0.42, purity (PE) of 95.82% and enrichment factor (Ef) of 1.92 were recorded with the optimum (Bmim)BF4/sulfate ILABS. These findings have provided an insight on the feasibility of recovery of intracellular biomolecules using the green solvent-based aqueous system in one single-step operation.
Deep eutectic solvents (DESs) are green solvents developed as an alternative to conventional organic solvents and ionic liquids to extract nitrogen compounds from fuel oil. DESs based on p-toluenesulfonic acid (PTSA) are a new solvent class still under investigation for extraction/separation. This study investigated a new DES formed from a combination of tetrabutylphosphonium bromide (TBPBr) and PTSA at a 1:1 molar ratio. Two sets of ternary liquid-liquid equilibrium experiments were performed with different feed concentrations of nitrogen compounds ranging up to 20 mol% in gasoline and diesel model fuel oils. More than 99% of quinoline was extracted from heptane and pentadecane using the DES, leaving the minutest amount of the contaminant. Selectivity was up to 11,000 for the heptane system and up to 24,000 for the pentadecane system at room temperature. The raffinate phase's proton nuclear magnetic resonance (1H-NMR) spectroscopy and GC analysis identified a significantly small amount of quinoline. The selectivity toward quinoline was significantly high at low solute concentrations. The root-mean-square deviation between experimental data and the non-random two-liquid (NRTL) model was 1.12% and 0.31% with heptane and pentadecane, respectively. The results showed that the TBPBr/PTSADES is considerably efficient in eliminating nitrogen compounds from fuel oil.
The production of lignin from empty fruit bunch (EFB) has been carried out using liquefaction method with 1-butyl-3-methylimidazolium chloride ([BMIM]Cl) ionic liquid (IL), in presence of sulfuric acid (H2SO4) as a catalyst. Response surface methodology (RSM) based on a factorial Central Composite Design (CCD) was employed to identify the optimum condition for lignin yield. The result indicated that the second order model was adequate for all the independent variables on the response with R(2)=0.8609. The optimum temperature, time, ionic liquid to EFB ratio, and catalyst concentration were 150.5 °C, 151 min, 3:1 wt/wt and 4.73 wt%, respectively for lignin yield=26.6%. The presence of lignin liquefied product was confirmed by UV-Vis and FTIR analysis. It was also demonstrated lignin extraction from lignocellulosic using recycled IL gave sufficient performance.
This study investigates the separation of two heavy metals, Cd(II) and Cu(II), from the mixed synthetic feed using a liquid-liquid extraction. The current study uses tri-octyl methylammonium chloride (Aliquat 336) as the extractant (with tributyl phosphate (TBP) as a phase modifier), diluted in toluene, in order to investigate the selective extraction of Cd(II) over Cu(II) ions. We investigate the use of ethylenediaminetetraacetic acid (EDTA) as a masking agent for Cu(II), when added in aqueous feed, for the selective extraction of Cd(II). Five factors that influence the selective extraction of Cd(II) over Cu(II) (the equilibrium pH (pHeq), Aliquat 336 concentration (Aliquat 336), TBP concentration (TBP), EDTA concentration (EDTA), and organic to aqueous ratio (O:A)) were analyzed. Results from a 25-1 fractional factorial design show that Aliquat 336 significantly influenced Cd(II) extraction, whereas EDTA was statistically significant for the antagonistic effect on the E% of Cu(II) in the same system. Moreover, results from optimization experiment showed that the optimum conditions are Aliquat 336 concentration of 99.64 mM and EDTA concentration of 48.86 mM-where 95.89% of Cd(II) was extracted with the least extracted Cu(II) of 0.59%. A second-order model was fitted for optimization of Cd(II) extraction with a R2 value of 0.998, and ANOVA results revealed that the model adequately fitted the data at a 5% significance level. Interaction between Aliquat 336 and Cd(II) has been proven via FTIR qualitative analysis, whereas the addition of TBP does not affect the extraction mechanism.
Poly(β-cyclodextrin functionalized ionic liquid) immobilized magnetic nanoparticles (Fe3O4@βCD-Vinyl-TDI) as sorbent in magnetic µ-SPE was developed for the determination of selected polycyclic aromatic hydrocarbons (PAHs) in rice samples coupled with gas chromatographic-flame ionization detector (GC-FID). The nanocomposite was characterized by various tools and significant parameters that affected the extraction efficiency of PAHs were investigated. The calibration curves were linear for the concentration ranging between 0.1 and 500 μg kg-1 with correlation determinations (R2) from 0.9970 to 0.9982 for all analytes. Detection limits ranged at 0.01-0.18 μg kg-1 in real matrix. The RSD values ranged at 2.95%-5.34% (intra-day) and 4.37%-7.05% (inter-day) precision for six varied days. The sorbents showed satisfactory reproducibility in 2.9% to 9.9% range and acceptable recovery values at 80.4%-112.4% were obtained for the real sample analysis. The optimized method was successfully applied to access content safety of selected PAHs for 24 kinds of commercial rice available in Malaysia.
An aqueous two-phase system (ATPS) with ionic liquids (ILs) was used for the isolate of C-phycocyanin (CPC) from Spirulina platensis microalga. Various imidazolium ILs and potassium salts were studied. The effect of ILs-ATPS on the extraction efficiency of CPC was also studied. The experimental parameters like pH, loading volume, algae concentration, temperature, and alkyl chain length of IL were well-covered in this report. The experimental results showed that the extraction efficiency, the partition coefficient, and the separation factor for CPC were 99%, 36.6, and 5.8, respectively, for an optimal pH value of 7 and a temperature of 308 K. The order of extraction efficiency for CPC using IL-ATPS was: 1-octyl-3-methylimidazolium bromide (C8MIM-Br) > 1-hexyl-3-methylimidazolium bromide (C6MIM-Br) > 1-butyl-3-methylimidazolium bromide (C4MIM-Br). The isolation process followed the pseudo second-order kinetic model and the thermodynamic results were obviously spontaneous.
Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.
A promising method of Carbon dioxide (CO2) valorization is to use green microalgae photosynthesis to process biofuel. Two Phase Partitioning Bioreactors (TPPBR) offer the possibility to use non-aqueous phase liquids (NAPL) to enhance CO2 solubility; thus making CO2 available to maximize algae growth. This requires relatively less toxic hydrophobic Ionic Liquids (ILs) that comprise a new class of ionic compounds with remarkable physicochemical properties and thus qualifies them as NAPL candidates. This paper concerns the synthesis of ILs with octyl and butyl chains as well as different cations containing aromatic (imidazolium, pyridinium) and non-aromatic (piperidinum, pyrrolidinium) rings for CO2 absorption studies. The authors measured their respective toxicity levels on microalgae species, specifically, Scenedesmus quadricauda, Chlorella vulgaris and Botryococcus braunii. Results revealed that octyl-based ILs were more toxic than butyl-based analogues. Such was the case for bmim-PF6 at double saturation with an absorbance of 0.11, compared to Omim-PF6 at 0.17, bmim-NTf2 at 0.02, and Omim-NTf2 at 0.14, respectively. CO2 uptake results for ILs bearing octyl-based chains compared to the butyl analog were 54% (nCO2/nIL) (i.e., moles of CO2 moles of IL) and 38% (nCO2/nIL), respectively. Conclusively, 1-butyl-1-methylpiperidinium absorbed 13% (nCO2/nIL) and appeared the least toxic, having an absorbance of 0.25 at 688 nm (double saturation at 7 d) compared to 1-butyl-3-methylimidazolium, which showed the highest toxicity with zero absorbance. Accordingly, these findings suggest that 1-butyl-1-methylpiperidinium is capable of transporting CO2 to a system containing green microalgae without causing significant harm; thus allowing its use in TPPBR technology.
The aim of this study was to investigate and apply supported ionic liquid membrane (SILM) in two-phase micro-electrodriven membrane extraction combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for pre-concentration and determination of three selected antidepressant drugs in water samples. A thin agarose film impregnated with 1-hexyl-3-methylimidazolium hexafluorophosphate, [C6MIM] [PF6], was prepared and used as supported ionic liquid membrane between aqueous sample solution and acceptor phase for extraction of imipramine, amitriptyline and chlorpromazine. Under the optimized extraction conditions, the method provided good linearity in the range of 1.0-1000μgL(-1), good coefficients of determination (r(2)=0.9974-0.9992) and low limits of detection (0.1-0.4μgL(-1)). The method showed high enrichment factors in the range of 110-150 and high relative recoveries in the range of 88.2-111.4% and 90.9-107.0%, for river water and tap water samples, respectively with RSDs of ≤7.6 (n=3). This method was successfully applied to the determination of the drugs in river and tap water samples. It is envisaged that the SILM improved the perm-selectivity by providing a pathway for targeted analytes which resulted in rapid extraction with high degree of selectivity and high enrichment factor.