Binary mixture of ionic liquid and span 80 for oil spill remediation: Synthesis and performance evaluation.

The synthesis of new surfactants helps to mitigate the environmental and financial effects of oil spills by providing efficient cleanup options. Herein, this study provides the development of a binary mixture of Span 80 and Choline myristate [Cho][Mys], a surface-active ionic liquid (SAIL) as green dispersant for oil spill remediation. The synergistic interaction at a 60:40 (w/w) ratio significantly lowered the critical micelle concentration (cmc) to 0.029 mM. Dispersion efficiency tests with Arab crude oil showed optimal performance at a 60:40 ratio of Span 80 and [Cho][Mys] (1:25 dispersant to oil ratio, v/v), achieving 81.16 % dispersion effectiveness in the baffled flask test. The binary mixture demonstrated superior emulsion stability (6 h) and the lowest interfacial tension (1.12 mN/m). Acute toxicity experiments revealed the dispersant's practical non-toxicity with an LC50 value of 600 mg/L. Overall, this environmentally benign surfactant combination shows promise as a safe and effective oil spill dispersant.

Simultaneous Purification of Human Interferon Alpha-2b and Serum Albumin Using Bioprivileged Fluorinated Ionic Liquid-Based Aqueous Biphasic Systems.

Interferon alpha-2b (IFN-α2b) is an essential cytokine widely used in the treatment of chronic hepatitis C and hairy cell leukemia, and serum albumin is the most abundant plasma protein with numerous physiological functions. Effective single-step aqueous biphasic system (ABS) extraction for the simultaneous purification of IFN-α2b and BSA (serum albumin protein) was developed in this work. Effects of the ionic liquid (IL)-based ABS functionalization, fluorinated ILs (FILs; [C​2C​1Im][C​4F​9SO​3] and [N​1112(OH)][C​4F​9SO​3]) vs. mere fluoro-containing IL ([C​4C​1Im][CF​3SO​3]), in combination with sucrose or [N​1112(OH)][H​2PO​4] (well-known globular protein stabilizers), or high-charge-density salt K​3PO​4 were investigated. The effects of phase pH, phase water content (%wt), phase composition (%wt), and phase volume ratio were investigated. The phase pH was found to have a significant effect on IFN-α2b and BSA partition. Experimental results show that simultaneous single-step purification was achieved with a high yield (extraction efficiency up to 100%) for both proteins and a purification factor of IFN-α2b high in the enriched IFN-α2b phase (up to 23.22) and low in the BSA-enriched phase (down to 0.00). SDS-PAGE analysis confirmed the purity of both recovered proteins. The stability and structure of IFN-α2b and BSA were preserved or even improved (FIL-rich phase) during the purification step, as evaluated by CD spectroscopy and DSC. Binding studies of IFN-α2b and BSA with the ABS phase-forming components were assessed by MST, showing the strong interaction between FILs aggregates and both proteins. In view of their biocompatibility, customizable properties, and selectivity, FIL-based ABSs are suggested as an improved purification step that could facilitate the development of biologics.

Multivariate optimization for extraction of 2-methylimidazole and 4-methylimidazole from açaí-based food products using polymeric ionic liquid-based sorbent coatings in solid-phase microextraction coupled to gas chromatography-mass spectrometry.

In this study, polymeric ionic liquids featuring different functional moieties were applied as sorbent coatings in direct-immersion solid-phase microextraction (DI-SPME) for the extraction of 2-methylimidazole (2-MI) and 4-methylimidazole (4-MI) from açaí-based food products followed by gas chromatography-mass spectrometry (GC-MS) analysis. The analytical method was optimized using a sequential experimental design. Variables used in GC-MS such as desorption time, as well as for SPME-DI, including extraction time, extraction temperature, incubation time of extraction, amount of NaCl in the extract, and stirring rate, were optimized. The fitness-for-purpose of the method was verified by the linearity of matrix-matched calibration curves (R2 ≥ 0.9921), adequate recoveries (81.7-89.7 %), and precision (relative standard deviations ≤11.2 %). The method was applied to twenty-five samples of açaí-based food products. 4-MI was found in four samples whereas 2-MI was not detected above the limit of detection. The method was found to be suitable for quality control analysis.

Efficient actinide sequestration with ionic liquid-based extraction chromatography resins containing Aza-crown ether functionalized diglycolamides.

Two new extraction chromatographic resins (ECRs) were prepared by impregnating two exotic diglycolamide (DGA) ligands (having three or four DGA moieties tethered to aza-crown ether scaffolds) dissolved in an ionic liquid onto an inert solid support. A room temperature ionic liquid (RTIL) was used for enhancing the performance of the ECRs. The ECR containing triaza-9-crown-3 functionalized with three DGA moieties (TAM-3-DGA), and tetraaza-12-crown-4 tethered with four DGA arms (TAM-4-DGA) were evaluated for the separation of Am3+ and Pu4+from nitric acid solutions. The resin capacity for Eu3+ was 9.52 mg/g and 7.24 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. Similarly, the resin capacity for Pu4+was 7.44 mg/g and 5.72 mg/g for TAM-3-DGA and TAM-4-DGA resins, respectively. These maximum loading values corresponded to the formation of a 1:1 metal/ligand complex for the Eu3+ ion and a 1:2 metal/ligand complex for the Pu4+ ion. The sorption of Eu3+and Pu4+on the resins followed a chemisorption phenomenon on both resins. The sorbed Eu3+and Pu4+ions from the resin phase could be efficiently desorbed with complexing ligands such as guanidine carbonate/HEDTA and oxalic acid, respectively.

Synthesis of lipophilic antioxidant tyrosol laurate using imidazolium ionic liquid [Bmim]HSO4 as a catalyst.

Tyrosol is a natural phenolic compound with potent antioxidant properties in the field of food manufacturing. However, the low lipophilicity of tyrosol limited its application. Therefore, the construction of tyrosol laurate (Tyr-L) could effectively overcome the limitations of tyrosol. In this work, four ionic liquids (ILs) were applied for TYr-L preparation. Among them, the 1-butyl-3-methylimidazolium hydrogen sulfate ([Bmim]HSO4) showed the best catalytic performance. The maximum TYr-L yield was achieved (94.24 ± 1.23 %) under the optimal conditions (reaction temperature 119 °C, substrate ratio 1:6.7, IL dosage 9.2 %, and reaction time 12 h). The kinetic and thermodynamic parameters were also evaluated and it was found that Ea, ΔH, ΔS, and ΔG were 80.81 kJ·mol-1, 77.63 kJ·mol-1, -82.08 J·(mol·K)-1, and 109.89 kJ·mol-1, respectively. The acidic [Bmim]HSO4 demonstrated excellent reusability and stability, even after 6 cycles. Furthermore, TYr-L showed superior ABTS radical scavenging ability, which could be further applied in various industrial processes.

Sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent-based capsule phase microextraction device combined with HPLC/post-column derivatization for the determination of lanreotide, a human somatostatin analogue in urine.

In this research, a sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent-based capsule phase microextraction (CPME) device was developed in combination with liquid chromatography-post column derivatization for the first ever reported determination of a somatostatin analogue - lanreotide in human urine. The sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent was encapsulated in the lumen of a polypropylene capillary tube and characterized by FT-IR spectroscopy and SEM with energy dispersive X-ray spectroscopy (EDS). The main steps of the CPME workflow were optimized to obtain high extraction efficiency for the target analyte. After the separation of the analyte on a C8 stationary phase, the peptide was derivatized online with o-phthalaldehyde before the fluorescence detection. The main experimental parameters of CPME and the post-column procedures were systematically investigated and optimized. The method was validated in terms of selectivity, linearity, accuracy, precision, limits of detection (LOD), and limits of quantification (LOQ). The relative bias ranged between 88.8 and 115.6 % for the peptide, while the RSD values for repeatability and intermediate precision were less than 14.3 %. The achieved limit of detection (LOD) was 0.2 µΜ while the limit of quantitation (LOQ) was established as 0.9 µΜ. Finally, the sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent-based microextraction capsules were found to be reusable for at least 20 extractions. The developed method presented adequate overall performance, and it could be applied in the analysis of selected peptide in human urine samples.

An immobilization of 2-(Aminomethyl) thiazole on multi-walled carbon nanotubes used for rapid extraction of manganese ions in hepatic patients.

A new method based on the immobilization of 2-(Aminomethyl) thiazole on the multi-walled carbon nanotubes (AMTZ@MWCNTs) was used to extract manganese (Mn) in the human blood, serum, and urine samples. First, 20 mg of AMTZ@MWCNTs, 0.2 mL of acetone, and 0.1 g of ionic liquid (IL) were completely mixed and injected into 2.0 mL human samples by a microscale syringe at pH 5.5. After shaking and centrifuging, the Mn ions were extracted and separated through the ultrasound-assisted- ionic liquid-dispersive micro solid-phase extraction (UAS-IL-D-µ-SPE) before being determined by the graphite furnace atomic absorption spectrometry (GF-AAS). According to the results, manganese in the blood of hepatic patients had higher concentrations than healthy people (Aged 25-60, 50 N). The Mn adsorption capacities for the AMTZ@MWCNTs and MWCNTs adsorbents were achieved at 192.5 mg/g and 26.3 mg/g, respectively. In the high enrichment factor (HEF), the limit of detection (LOD), linear range (LR), and mean relative standard division (RSD%) were calculated at 15 ng/L, 0.05-3.8 µg/L, and 2.34, respectively (n = 10). The methodology was validated using certified reference material (CRM) and spiking standard solutions to human samples.

Development of Cholinium-Based API Ionic Liquids with Enhanced Drug Solubility: Biological Evaluation and Interfacial Properties.

We report an efficient sustainable two-step anion exchange synthetic procedure for the preparation of choline API ionic liquids (Cho-API-ILs) that contain active pharmaceutical ingredients (APIs) as anions combined with choline-based cations. We have evaluated the in vitro cytotoxicity for the synthesized compounds using three different cells lines, namely, HEK293 (normal kidney cell line), SW480, and HCT 116 (colon carcinoma cells). The solubility of APIs and Cho-API-ILs was evaluated in water/buffer solutions and was found higher for Cho-API-ILs. Further, we have investigated the antimicrobial potential of the pure APIs, ILs, and Cho-API-ILs against clinically relevant microorganisms, and the results demonstrated the promise of Cho-API-ILs as potent antimicrobial agents to treat bacterial infections. Moreover, the aggregation and adsorption properties of the Cho-API-ILs were observed by using a surface tension technique. The aggregation behavior of these Cho-API-ILs was further supported by conductivity and pyrene probe fluorescence. The thermodynamics of aggregation for Cho-API-ILs has been assessed from the temperature dependence of surface tension. The micellar size and their stability have been studied by dynamic light scattering, transmission electron microscopy, and zeta potential. Therefore, the duality in the nature of Cho-API-ILs has been explored with the upgradation of their physical, chemical, and biopharmaceutical properties, which enhance the opportunities for advances in pharmaceutical sciences.

New ionic liquids based on 5-fluorouracil: Tuning of BSA binding and cytotoxicity.

In this work, we describe the synthesis, interactions with bovine serum albumin, and cytotoxicity of new ionic liquids based on 5-fluorouracil (API-ILs) with different cations (imidazolium, choline, isoquinolinium, guanidinium). The secondary and tertiary structure of BSA in solutions with different concentrations of API-ILs was monitored by the circular dichroism (CD) technique. The addition of API-ILs does not lead to structural changes in BSA. A quenching of fluorescence spectra intensity of BSA in presence of all API-ILs was observed, allowing the quantification of binding between API-ILs and BSA. The preferred localization of both ions in API-ILs differs significantly depending on the structure of the cation according to molecular docking. The aggregation of BSA in presence of API-ILs was analyzed by the dynamic light scattering (DLS) method, revealing a moderate increase in particle size. Cytotoxicity and selectivity of API-ILs on cancer and normal cell lines were estimated, showing a clear modification of the pharmaceutic activity of ionic liquid compared to 5-fluorouracil.

Effects of cationic head group structure on cytotoxicity and mitochondrial actions of amphiphilic ionic liquids.

Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties that make them suitable for a range of industrial applications. Accumulating evidence suggests that certain ILs are cytotoxic and potential environmental pollutants, thus understanding the structural features that promote IL cytotoxicity is important. Amphiphilic ionic liquids (AmILs), a class of ILs with lipophilic N-alkyl chains, containing aromatic head groups are generally more cytotoxic than their aliphatic counterparts, however the impact of other head group properties are less clear. This study therefore sought to provide new structure activity relationship (SAR) insights regarding the role of the cationic head group on AmIL cytotoxicity. A series of AmILs bearing a range of structurally diverse aromatic cations varying in size, charge, and lipophilicity was synthesised and screened against human MDA-MB-231 breast cancer cells. It was found that larger and more lipophilic head groups increased cytotoxicity, although the magnitude of the changes were modest. The mitochondrial effects of representative ILs were assessed. The AmILs induced mitochondrial dysfunction in MDA-MB-231 cells at cytotoxic concentrations, suggesting that they target mitochondria. The new SAR information from this study may assist in the design of AmILs with controlled cytotoxicity.

Efficient extraction performance and mechanisms of Cd2+ and Pb2+ in water by novel dicationic ionic liquids.

Ten novel hydrophobic dicationic ionic liquids (DILs) were synthesized and applied for the extraction of heavy metals in aqueous solutions. Their physicochemical properties were measured at ambient temperature, and the leaching behaviors of the as-prepared DILs in water were assessed by TOC analysis. Metal extraction experiments were carried out to evaluate the extraction performances of the DILs. It was found that the extraction rates of up to 0.45 and 0.53 mg·(g·min)-1 were achieved with 100 mg DILs for 5 mL of 5 mg/L Cd2+ and Pb2+ solutions. Besides, the extraction efficiencies of Cd2+ and Pb2+ were respectively up to 95.48% and 98.46%, when the volumes of the simulated wastewater were expanded by a factor of 20 at a constant extraction phase ratio (1000 mg DILs for 50 mL of 5 mg/L Cd2+ or Pb2+ solutions). The reusability of the novel DILs was successfully proved by the back-extraction experiments with 0.5 M HNO3. Finally, taking Cd2+ extraction as an example, the extraction mechanism based on FTIR analysis and quantum chemical calculations showed that both S and O atoms in the anions of DILs had physical and quasi-chemical interactions with Cd2+, which were stronger than the electrostatic attraction.

Polymeric ionic liquid sorbent coatings in thin film microextraction: Insight into sorbent selectivity for pesticides and cannabinoids.

Polymeric ionic liquid (PIL) sorbent coatings consisting of polymerizable cations and anions were employed as sorbent coatings in thin film microextraction (TFME) for the extraction of pesticides and cannabinoids. The blades consisted of a thin film of PIL sorbents chemically bonded to vinyltrimethoxysilane-functionalized nitinol sheets. The imidazolium- or ammonium-based PIL sorbents contained aromatic benzyl moieties as well as polar hydroxyl groups or aliphatic functional groups within the chemical structure of the IL monomer. The chemical structure of the IL crosslinkers of the PILs were kept constant across each sorbent, except for the anion, which consisted of either bis[(trifluoromethyl)sulfonyl]imide ([NTf2-]), p-styrenesulfonate ([SS-]), or 3-sulfopropyl acrylate ([SPA-]). Temperature, salt content, and methanol content were optimized as extraction conditions to maximize pesticide-cannabinoid selectivity using Doehlert design of experiments (DOE). Effects of these three factors on selectivity and extraction efficiency are discussed. The optimal extraction conditions consisting of sample temperature (31°C), sodium chloride (30% w/v), and methanol content (0.25% v/v) are compared to initial sorbent screening conditions at a sample temperature of 40°C, 15% (w/v) sodium chloride, and 2.5% (v/v) methanol content. PIL sorbent swelling behavior at different salt and methanol content conditions and its effect on extraction efficiency are hypothesized. Selectivity factors for the sorbents indicated that aromatic moieties within the IL monomer may enhance pesticide-cannabinoid selectivity under optimized conditions, but the extraction efficiency of pesticides that are known to coelute with cannabinoids in the chromatographic separation may be enhanced by employing sorbent coatings with [SPA-] anions.

Progress in the application of ionic liquids and deep eutectic solvents for the separation and quantification of per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFASs), often labeled as "forever chemicals," earned this moniker due to their widespread presence in the environment, bioaccumulative tendencies, and resistance to remediation efforts. Employed for decades in various applications, spanning from stain-resistant fabrics to grease-proof food containers and fire-fighting foams, PFASs have evolved into an anthropogenic nightmare. Their adverse impact on human health, including immune dysfunction, infertility, and a spectrum of cancers, is alarming. Conventional water treatment methods, notably in the case of short-chain congeners, struggle to effectively eliminate PFASs, underscoring the pressing need for enhanced adsorbents. In recent years, there has been a prominent surge in the exploration of innovative techniques centered around ionic liquids (ILs) and deep eutectic solvents (DESs) for the removal of PFASs from various sources, including food samples like cooking oil, as well as environmental waters. In this Review, we delve into key advancements and discoveries related to the utilization of ILs and DESs as media for the liquid-liquid extraction of PFASs, as well as their applications as sorbents on solid-state or nanoscale supports. Our exploration encompasses groundbreaking approaches, including the utilization of dicationic ILs for ultra-sensitive mass spectrometric PFAS detection, alongside the innovative application of fluorinated ILs and hydrophobic DESs, enabling highly efficient PFAS sequestration. The landscape of existing PFAS extraction methods is riddled with formidable challenges, including limited selectivity, matrix interferences, subpar extraction efficiency, exorbitant costs, laborious procedures, ecological consequences, and a lack of standardization. Given these challenges, our review unequivocally asserts the pivotal role ILs and DESs will play in shaping the next generation of PFAS remediation strategies. Rigorous characterization of water solubility, toxicity, and biodegradation, along with improved recyclability and thorough techno-economic analyses, are essential for further progress. Future focus must also extend to addressing short-chain PFASs (such as PFBS) and PFAS alternatives (including ADONA, GenX, F-53B), which often pose higher toxicity risks than the compounds they aim to replace. A forward-thinking approach will integrate cutting-edge data-driven techniques, such as machine learning, to enhance our understanding and response to PFAS-related issues. Finally, we advocate seamless integration of PFAS separation with advanced treatment, efficiently isolating and destroying these compounds for a lasting solution to contamination challenges.

Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride.

For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by 1H NMR translation self-diffusometry and is further corroborated by 13C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (pb) and equivalent partition coefficient (K) of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates (R1SEL and R1NS, respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.

Optimization of [P6,6,6,14+]3[GdCl63-] magnetic ionic liquid assisted dispersive liquid-liquid microextraction for selective and sensitive determination of cadmium in environmental water and food.

A simple and green hydrophobic magnetic ionic-liquid assisted dispersive liquid-liquid microextraction (MIL-DLLME) was optimized for the determination of trace cadmium (Cd (II)) in environmental and food samples by flame atomic absorption spectrophotometer. To achieve selective and sensitive extraction of Cd (II), four MILs were prepared and tested. Extraction parameters of the MIL-DLLME including pH, type and volume of the MIL, type and volume of dispersive solvent, extraction cycle, ionic strength and sample volume were investigated in detail and optimized by Box-Behnken design. Under optimum conditions, matrix effect, recovery study, intra-day and inter-day precision were performed for the MIL-DLLM. The analytical characteristics such as limit of detection, limit of quantification and pre-concentration factor were 0.17, 0.56 and 125 ng mL-1, respectively. The validation of the MIL-DLLME was evaluated by analysis of reference materials. Moreover, the accuracy of the results in the analysis of real samples was evaluated by standard addition and quantitative recoveries (91 ± 5-101 ± 2%) were achieved. The results obtained in the analysis of both reference materials and real samples showed that the MIL-DLLME has a selective applicability for cadmium.

Counteraction Effects of Ammonium-Based Ionic Liquids on Urea-Induced Denaturation of α-Lactalbumin: A Comprehensive Molecular Simulation Study.

Ionic liquids (ILs) are known to stabilize protein conformations in aqueous medium. Importantly, ILs can also act as refolding additives in urea-driven denaturation of proteins. However, despite the importance of the problem, detailed microscopic understanding of the counteraction effects of ILs on urea-induced protein denaturation remains elusive. In this work, atomistic molecular dynamics (MD) simulations of the protein α-lactalbumin have been carried out in pure aqueous medium, in 8 M binary urea-water solution and in ternary urea-IL-water solutions containing ammonium-based ethyl ammonium acetate (EAA) as the IL at different concentrations (1-4 M). Attempts have been made to quantify detailed molecular-level understanding of the origin behind the counteraction effects of the IL on urea-induced partial unfolding of the protein. The calculations revealed significant conformational changes of the protein with multiple free energy minima due to its partial unfolding in binary urea-water solution. The counteraction effect of the IL was evident from the enhanced structural rigidity of the protein with propensity to transform into a single native free energy minimum state in ternary urea-IL-water solutions. Such an effect has been found to be associated with preferential direct binding of the IL components with the protein and simultaneous expulsion of urea from the interface, thereby providing additional stabilization of the protein in ternary solutions. Most importantly, modified rearrangement of the hydrogen bond network at the interface due to the formation of stronger protein-cation (PC) and protein-anion (PA) hydrogen bonds by breaking relatively weaker protein-urea (PU) and protein-water (PW) hydrogen bonds has been recognized as the microscopic origin behind the counteraction effects of EAA on urea-induced partial unfolding of the protein.

Efficient asymmetric synthesis of ethyl (R)-3-hydroxybutyrate by recombinant Escherichia coli cells under high substrate loading using eco-friendly ionic liquids as cosolvent.

Ionic liquids (ILs) which synthesized from bio-renewable materials have recently attracted much attention for their applications in biocatalysis. Ethyl (R)-3-hydroxybutyrate ((R)-EHB) as a versatile chiral intermediate is of great interest in pharmaceutical synthesis. This study focuses on evaluating the performances of choline chloride (ChCl)-based and tetramethylammonium (TMA)-based neoteric ILs in the efficient synthesis of (R)-EHB via the bioreduction of ethyl acetoacetate (EAA) at high substrate loading by recombinant Escherichia coli cells. It was found that choline chloride/glutathione (ChCl/GSH, molar ratio 1:1) and tetramethylammonium/cysteine ([TMA][Cys], molar ratio 1:1) as eco-friendly ILs not only enhanced the solubility of water-insoluble EAA in the aqueous buffer system, but also appropriately improved the membrane permeability of recombinant E. coli cells, thus boosting catalytic reduction efficiency of EAA to (R)-EHB. In the developed ChCl/GSH- or [TMA][Cys]-buffer systems, the space-time yields of (R)-EHB achieved 754.9 g/L/d and 726.3 g/L/d, respectively, which are much higher than neat aqueous buffer system (537.2 g/L/d space-time yield). Meanwhile, positive results have also been demonstrated in the bioreduction of other prochiral ketones in the established IL-buffer systems. This work exhibits an efficient bioprocess for (R)-EHB synthesis under 325 g/L (2.5 M) substrate loading, and provides promising ChCl/GSH- and [TMA][Cys]-buffer systems employed in the biocatalysis for hydrophobic substrate.

Non-Invasive Transdermal Delivery of Antisense Oligonucleotides with Biocompatible Ionic Liquids.

Nucleic acid drugs, including antisense oligonucleotides (ASOs), have received considerable attention as novel therapeutics for the treatment of intractable diseases. Despite their potential benefits, ASOs are currently administered via injection, which can negatively impact patient quality of life because of the prevalence of severe injection site reactions. Non-invasive transdermal administration of ASOs is desirable but highly challenging owing to the strong barrier imposed by the stratum corneum, which only permits the penetration of small molecules under 500 Da. For ASOs to exert their antisense effect, they must traverse the negatively charged cell membrane and reach the cytoplasm. In this study, we used the solid-in-oil (S/O) dispersion technology to facilitate the skin permeation of ASOs by coating the drug with a hydrophobic surfactant molecule, specifically lipid-based ionic liquid (IL) surfactants with high biocompatibility and transdermal penetration-enhancing properties. To induce the antisense effect, it was important to achieve simultaneous transdermal delivery and intracellular entrapment of ASOs. In vitro investigations indicated that the newly prepared IL-S/O enhanced the transdermal penetration and intracellular delivery of ASOs, thus inhibiting mRNA translation of the target TGF-ß. In addition, in vivo investigations of tumor-bearing mice suggested that the anti-tumor effect of the IL-S/O was similar to that of injection. This study demonstrates the potential of non-invasive transdermal delivery carriers based on biocompatible ILs, which can be applied to a variety of nucleic acid drugs.

A FTIR and DFT Combination Study to Reveal the Mechanism of Eliminating the Azeotropy in Ethyl Propionate-n-Propanol System with Ionic Liquid Entrainer.

Ionic liquids (ILs) have presented excellent behaviors in the separation of azeotropes in extractive distillation. However, the intrinsic molecular nature of ILs in the separation of azeotropic systems is not clear. In this paper, Fourier-transform infrared spectroscopy (FTIR) and theoretical calculations were applied to screen the microstructures of ethyl propionate-n-propanol-1-ethyl-3-methylimidzolium acetate ([EMIM][OAC]) systems before and after azeotropy breaking. A detailed vibrational analysis was carried out on the v(C=O) region of ethyl propionate and v(O-D) region of n-propanol-d1. Different species, including multiple sizes of propanol and ethyl propionate self-aggregators, ethyl propionate-n-propanol interaction complexes, and different IL-n-propanol interaction complexes, were identified using excess spectroscopy and confirmed with theoretical calculations. Their changes in relative amounts were also observed. The hydrogen bond between n-propanol and ethyl propionate/[EMIM][OAC] was detected, and the interaction properties were also revealed. Overall, the intrinsic molecular nature of the azeotropy breaking was clear. First, the interactions between [EMIM][OAC] and n-propanol were stronger than those between [EMIM][OAC] and ethyl propionate, which influenced the relative volatilities of the two components in the system. Second, the interactions between n-propanol and [EMIM][OAC] were stronger than those between n-propanol and ethyl propionate. Hence, adding [EMIM][OAC] could break apart the ethyl propionate-n-propanol complex (causing the azeotropy in the studied system). When x([EMIM][OAC]) was lower than 0.04, the azeotropy still existed mainly because the low IL could not destroy the whole ethyl propionate-n-propanol interaction complex. At x(IL) > 0.04, the whole ethyl propionate-n-propanol complex was destroyed, and the azeotropy disappeared.

Rapid extraction of osimertinib and its active metabolite in urine by miniaturized centrifugal spin-column extraction using ionic liquid hybrid hierarchical porous adsorbent.

Osimertinib (OSIM) is widely used as a mainstream drug for the treatment of non-small cell lung cancer (NSCLC). However, the lack of a rapid extraction and detection method for OSIM and its metabolite, AZ-5104, has limited clinical drug metabolism and drug resistance research because the drug is unstable. In this study, a new ionic liquid hybrid hierarchical porous material (IL-HHPM) was synthesized with hierarchical porous structures, including micropores (1.6-2.0 nm), mesopores (2.0-50.0 nm), macropores (50.0-148.7 nm), and multiple functional groups via a one-step hydrothermal method using silanized ionic liquids (IL) as functionalized hybrid monomer. The IL-HHPM has the advantages of a high specific surface area (437.4 ± 4.6 m2 g-1), sizable pore volume (0.74 cm3 g-1), and fast mass transfer, additionally, the IL-HHPM adsorbed OSIM and AZ-5104 via π-π interactions and hydrogen bonding. OSIM and AZ-5104 were rapidly extracted and measured in human urine using rapid and miniaturized centrifugal spin-column extraction (MCSCE), which was based on the IL-HHPM. The optimized factors for the extraction recoveries of OSIM and AZ-5104 were adsorbent dosage (8.0 mg), sample volume (0.5 mL), and operation time (9.0 min), and markedly reduced the adsorbent dosage and operation time. The IL-HHPM-MCSCE-HPLC method displayed good linearity (0.02-5.00 µg mL-1, r ≥ 0.9997), satisfying accuracy (spiked recoveries of 87.7%-100.0%), and good precision (RSDs ≤ 7.0%). The developed method is rapid, sensitive, and reproducible for the simultaneous determination of trace level of OSIM and AZ-5104 in human urine.