IL Concentration Research Articles

Inhibition of Aβ16-22 Aggregation by [TEA]+[Ms]- Follows Weakening of the Hydrophobic Core and Sequestration of Peptides in Ionic Liquid Nanodomains.

We developed a coarse-grained model for the protic ionic liquid, triethylammonium mesylate ([TEA]+[Ms]-), to characterize its inhibitory effects on amyloid aggregation using the K16LVFFAE22 fragment of the amyloid-β (Aβ16-22) as a model amyloidogenic peptide. In agreement with previous experiments, coarse-grained molecular dynamics simulations showed that increasing concentrations of [TEA]+[Ms]- in aqueous media led to increasingly small Aβ16-22 aggregates with low beta-sheet contents. The cause of [TEA]+[Ms]-'s inhibition of peptide aggregation was found to be a result of two interrelated effects. At a local scale, the enrichment of interactions between [TEA]+ cations and hydrophobic phenylalanine side chains weakened the hydrophobic cores of amyloid aggregates, resulting in poorly ordered structures. At a global level, peptides tended to localize at the interfaces of IL-rich nanostructures with water. At high IL concentrations, when the IL-water interface was large or fragmented, Aβ16-22 peptides were dispersed in the simulation cell, sometimes sequestered at unaggregated monomeric states. Together, these phenomena underlie [TEA]+[Ms]-'s inhibition of amyloid aggregation. This work addresses the critical lack of knowledge on the mechanisms of protein-ionic liquid interactions and may have broader implications for industrial applications.

Construction of PEO@g-C3N4 supported ionic liquid membrane with interactive network structure for enhanced carbon capture efficiency

Polyethylene oxide (PEO) shows a high CO2-philic due to its dipolar-quadrupolar interaction with CO2 molecules. As a result, it is an excellent candidate for gas separation applications, yet it faces problems such as crystallization and low permeance. Herein, we show a versatile strategy to enhance gas permeation fluxes, which is mainly achieved by hindering the crystallization of PEO and the stacking of nanosheets. Specifically, graphite-like phase carbon nitride (g-C3N4) nanosheets are introduced and interaction networks (PGCN) are constructed by taking full advantage of the dipole-level quadrupole moment interactions between the ether-oxygen groups contained in PEO and CO2. In order to compensate the membrane surface defects for enhancing gas selectivity, we used the suspension coating method to create a PEO@g-C3N4 supported ionic liquid membrane (PGCN/ILX SILM) by coating IL on the surface of membrane. The results show that, when the IL concentration is 30 wt%, the PGCN/IL30 % membrane separates CO2/N2 with a CO2 permeance of 1396 GPU and an optimal selectivity of 58. While overcoming the “Trade-off” effect, it has demonstrated good thermal stability and long-term stable operation for 72 h. The development of this work will generate solutions for overcoming PEO crystallization and achieving efficient CO2 capture.

Effect of water and ionic liquid vapors on the structural properties of gold nanoclusters formed during inert-gas condensation process using molecular dynamics simulations

In this research, process of Au nanocluster formation has been investigated using the inert-gas condensation process in different environments with different concentrations of Ar gas, water vapor, and IL molecules. We have calculated the total energy, relative stability, surface energy, and radial distribution function (RDF) of the different produced clusters at different simulation times. Our results showed that the number of formed clusters increases, whereas their size decreases by increasing the water and IL concentrations in the environment. The water and IL molecules adsorb on the nanoclusters surfaces and hinder the coalescence of the smaller clusters to form bigger clusters. The percentage of the fcc and hcp atoms also decreases by increasing the water and IL concentrations. The produced clusters also become more non-spherical by increasing the IL and water vapor in the environment (with exception of the pure vapors).

Application of ionic liquid ultrasound-assisted extraction (IL-UAE) of lycopene from guava (Psidium guajava L.) by response surface methodology and artificial neural network-genetic algorithm

Lycopene-rich guava (Psidium guajava L.) exhibits significant economic potential as a functional food ingredient, making it highly valuable for the pharmaceutical and agro-food industries. However, there is a need to enhance the extraction methods of lycopene to fully exploit its beneficial uses. In this study, we evaluated various ionic liquids to identify the most effective one for extracting lycopene from guava. Among thirteen ionic liquids with varying carbon chains or anions, 1-butyl-3-methylimidazolium chloride demonstrated the highest productivity. Subsequently, a single-factor experiment was employed to test the impact of several parameters on the efficiency of lycopene extraction using this selected ionic liquid. These parameters included extraction time, ultrasonic power, liquid-solid ratio, concentration of the ionic liquid, as well as material particle size. Moreover, models of artificial neural networks using genetic algorithms (ANN-GA) and response surface methodology (RSM) were employed to comprehensively assess the first four key parameters. The optimized conditions for ionic liquid ultrasound-assisted extraction (IL-UAE) were determined as follows: 33 min of extraction time, 225 W of ultrasonic power, 22 mL/g of liquid-solid ratio, 3.0 mol/L of IL concentration, and extraction cycles of three. Under these conditions, lycopene production reached an impressive yield of 9.35 ± 0.36 mg/g while offering advantages such as high efficiency, time savings, preservation benefits, and most importantly environmental friendliness.

Comprehensive Analysis of the Acute Toxicity of Ionic Liquids Using Microtox® Bioassays

The ecotoxicity of a set of 30 ionic liquids, namely 23 aprotic compounds (APILs) and 7 protic compounds (PILs), was analyzed in this work by monitoring the inhibition of the bioluminescence of the bacteria Aliivibrio fischeri with varying concentrations of ILs utilizing the Microtox® standard toxicity test. The study covered ILs that have various synthetic natures, PILs and APILs, with a common anion or cation, and different alkyl chain lengths. The results indicate that both moieties, anion and cation, have an influence on toxicity, these being the ILs with the bis((trifluoromethyl)sulfonyl)imide (TFSI) anion and imidazolium cation, which are the most harmful, while those less toxic correspond to ammonium-based ILs. The alkyl chain length seems to have the most significant impact on toxicity, except for tris(pentafluoroethyl) trifluorophosphate (FAP) anion-based ILs, which, interestingly, showed the opposite behavior. A critical alkyl size (CAS) at C = 6 was observed for the rest of the families, resulting in a significant reduction in the effective concentration (EC) values: the connection between this CAS and toxicity has never been observed before, and it indicates a threshold that marks the end of harmlessness (C < 6) and the start of toxicity (C > 6).

An insight on reaction kinetics of amino-acid-functionalized ionic liquid monoethanolamine glycinate for CO2 capture

ABSTRACT Recently, the application of functionalized ionic liquids in carbon dioxide (CO2) capture has received significant attention. In this research, the absorption kinetics of CO2 into the aqueous amino-acid-functionalized monoethanolamine glycinate ionic liquid in a stirred cell reactor was investigated. Amino acids are less volatile and have good resistance against oxidative degradation. Experiments were accomplished over a temperature range of 298–308 K and solution concentrations ranging from 0.5 to 2.5 M in the pseudo-first-order regime. The dimensionless Hatta number and infinite enhancement factor were calculated to check the fast pseudo-first-order reaction assumption. The reaction rate constant has been evaluated by recording the system pressure reduction rate over time. Increasing the IL concentration and temperature results in a significant increase in the reaction rate. The obtained kinetic constants have the same order of magnitude as those existing for primary amines.

Amino acid-based ionic liquid as a promising CO2 sorption increasing agent by aqueous MDEA solution

The present study aims to enhance the efficiency of CO2 absorption by aqueous MDEA solutions and reduce the energy consumption of the process by designing combined absorbent systems. For this, a novel ionic liquid based on the amino acid glycine, known as bis(2-hydroxyethyl)dimethylammonium glycinate ([M2E2A][Gly]), was synthesized and investigated as a carbon dioxide sorbent. The composition was confirmed using 1H NMR. The sorption capacity of neat [M2E2A][Gly], its aqueous solutions and amine + IL aqueous mixtures was evaluated gravimetrically at different temperatures and concentrations of comprising components. The study observed an increase in both the sorption capacity and the rate of chemical reaction with carbon dioxide when using this compound as an additive. The H2O/MDEA/[M2E2A][Gly] absorbent (50/30/20 wt%) exhibited the highest sorption capacity of 2.98 mol CO2·kg-1solution. Furthermore, a mechanism of CO2 interaction with the H2O/MDEA/[M2E2A][Gly] absorbent was suggested and confirmed using FTIR spectroscopy. To assess the effect of the IL concentration on the absorbent’s viscosity behavior, studying rheological properties of absorbent with different contents of [M2E2A][Gly] were studied.

Machine Learning-Guided Adaptive Parametrization for Coupling Terms in a Mixed United-Atom/Coarse-Grained Model for Diphenylalanine Self-Assembly in Aqueous Ionic Liquids.

Precise regulation of the peptide self-assembly into ordered nanostructures with intriguing properties has attracted intense attention. However, predicting peptide assembly at atomic resolution is a challenge due to both the structural flexibility of peptides and the associated huge computational costs. A machine learning-guided adaptive parametrization method was proposed for developing a mixed atomic and coarse-grained (CG) model through a multiobjective optimization strategy. Our model incorporates the united-atom (UA) model for diphenylalanine (P) and the polarizable electrostatic-variable coarse-grained (VaCG) model for aqueous ionic liquid [BMIM]+[BF4]- solution. In this mixed model, the coupling van der Waals (vdW) interaction is addressed by introducing virtual sites (VS) in the UA model to interact with solvent CG beads. The coupling parameters, including the electrostatic parameter and vdW parameters, are automatically optimized through ML-guided adaptive parametrization. The performance of this model was tested by some microstructural properties, e.g., the average number of P-P intermolecular hydrogen bonds (HBs) and radius distribution functions (RDFs) between P and different fragments of IL, in comparison with all-atom (AA) simulations. The computational cost is significantly reduced using such a parametrization scheme, which could search tens of thousands of force-field parameter sets, while needing only a small fraction of them to be assessed with molecular dynamics (MD) simulations. We used such a mixed resolution model to investigate the self-assembly in IL-water mixtures with variants of IL concentration (X). The long-range-ordered fibril structure is formed in a pure water system (X = 0). With an increase of IL concentrations, the formation of an ordered self-assembly nanostructure is prohibited, instead forming branched fibril at X = 2 mol % or amorphous aggregates when X > 10 mol %, resulting from the interplay between π-stacking and HB interactions between P and IL. The qualitative agreement between the simulated structures and the observed morphologies in experiments indicates the applicability of ML-guided parametrization strategy in the study of complex systems, such as polymers, lipid bilayers, and polysaccharides.

Efficient CO2 separation by ionic liquid nanoconfined in ultra-thin TCOH@Pebax-1657 MMM

Global climate change has continued to intensify in recent years, and the low efficiency of carbon emission reduction has become an important issue for many countries. Membrane separation technology has gained popularity in CO2 capture due to its ease of operation, environmental friendliness, and smaller area, etc. Two-dimensional (2D) sheet materials are one of the most promising materials for membrane separation technology. MXene has been used for gas separation because of its advantages such as high aspect ratio, excellent flexibility, and rich functional group surface. However, the stacking of massive MXene nanosheets lead to gas transport channel obstruction, causing the gas permeance to decrease. Herein, the hydroxylation of MXene was treated to obtain alkaline MXene nanosheets (TCOH) in this work. The stabilised TCOH and Pebax-1657 were used to make a mixed matrix membrane (MMM), while 1-ethyl-3-methylimidazolyl acetate ([EMIm][AcO], IL) was nanoconfined in the 2D channel of ultra-thin TCOH@Pebax-1657 MMM to construct a novel composite membrane for efficient CO2 capture. The TCOH@Pebax-1657/IL membrane prepared in this experiment has high CO2 permeance and the selectivity of CO2/N2, CO2/CH4 at the IL concentration of 35 wt%. In addition, the film has shown excellent thermal stability and durability over long periods of testing. Since TCOH is rarely used in the field of gas separation, the study will provide fresh idea for the preparation of highly efficient CO2 capture membranes.

Influences and mechanisms of imidazolium-based ionic liquids on oil–water interfacial tension and quartz wettability: Experiment and molecular dynamics simulations

Interfacial tension (IFT) and wettability are two key parameters determining pore-scale oil/water distributions and reservoir-scale hydrocarbon production performances. However, how ionic liquid (IL, a green, stable, and efficient chemical) will manipulate IFT and wettability for EOR in sandstone reservoirs has not been sufficiently investigated yet, and the underlying mechanisms at the micro-level are still unknown. In this study, the influences of two typical ILs at various concentrations (i.e., 0.01, 0.1, 1, and 5 mmol/L) on oil–water IFT and alpha-quartz (α-quartz) wettability were investigated. This study shows that low concentrations of ILs can greatly reduce alkane-water IFT, and gemini IL has higher interfacial activity than mono-cationic IL, which is due to the fact that gemini IL with longer alkyl chains is more likely to form conglomerates at lower concentrations. Both the advancing and receding contact angles increase continuously with concentration in ILs solution, which can be given responsibility for the decrease in IFT and the solid–liquid interaction resulting in an increased capacity of alkane droplets to migrate on the α-quartz surface. Additionally, the molecular dynamic simulations examined the micro-wetting process and interaction energy of the IL-alkane-quartz system, and revealed that ILs can effectively reduce interaction energy between octane droplets and α-quartz surface. These insights have promising applications to enhanced oil recovery and oil contamination removal at subsurface.

Impact of diphenhydramine hydrochloride on an aqueous solution of imidazolium based surface-active ionic liquids at different temperatures: Physicochemical, thermodynamic and transport studies

In order to embrace the synergy between drug diphenhydramine hydrochloride (DPH) and ionic liquids 1-decyl-3-methylimidazolium bromide [C10mim][Br] and 1-dodecyl-3-methylimidazolium bromide [C12mim][Br] in aqueous media, we investigated the thermodynamics and transport properties of binary and ternary system. The calculation of quantities such as apparent molar volume (Vϕ), limiting apparent molar volume (Vοϕ), apparent molar isentropic compressibility (Kϕ) and limiting apparent molar isentropic compressibility (Kοϕ) of DPH in aqueous solution of ionic liquids from the volumetric and acoustic data help us to explore the solute–solute as well as solute–solvent interaction existing in the ternary systems. The apparent molar expansivity (Eoϕ), Hepler's constant (∂Eoϕ/∂T)P have been further determined to assist the interpretations earned from the volumetric and acoustic analysis. In addition, using the Jones–Dole equation, viscosity B-coefficients and temperature derivative of B-coefficients (dB/dT) have been determined. By using co-sphere overlap model of ternary mixtures we have studied the different types of interaction prevailing in the DPH and aqueous ionic liquids solution. The dominance of ionic-hydrophilic and hydrophilic-hydrophilic interactions in the ternary system is indicated by the positive and increasing ΔtrVϕ0 and ΔtrKοΦ values with increasing ILs concentration. Finally, the structure making nature of the DPH in aqueous ionic liquid solution is confirmed by the Hepler’s constant and viscosity B- coefficients.

Distribution of alternate site infusion providers in the US.

1542 Background: Spurred by the pandemic, chemotherapy treatments provided by alternate site infusion providers have been increasing. This diversification has the potential to increase access to care and improve patient satisfaction. However, it is currently unknown how equitably distributed these non-traditional infusion settings are, and whether these newer entrants are entering markets with need or markets with ample supply. In addition, many community oncologists are concerned about the ability to retain control over a patient’s treatment and preserve the profits earned from drug infusions. Further, there are concerns regarding the lack of robust data on the safety of alternate site chemotherapy infusions. Industry analysts anticipate steady expansion in US markets for alternate site infusion with chemotherapy being a strong driver of growth. The objective of this study was to examine the distribution of alternate site infusion services across the US. Methods: Leveraging the Medicare home health infusion (MHHI) provider database from CMS, we calculated the rate of MHHI providers per 1000 Medicare beneficiaries in each US state. We reviewed company information to determine the geographic footprint of 3 alternate site infusion providers. Results: The median MHHI rate was 0.013 per 1000 beneficiaries (CO), the average rate was 0.031, with a minimum of 0 (ND, SD, WY) and a maximum of 0.202 (IL). ND, SD, WY, IN, KY, and OK have the lowest concentration of MHHI providers, whereas OR, KS, WA, NE, CA, and IL have the highest concentration. 3 alternate site infusion providers are Option Care, UnitedHealth’s Optum Infusion Pharmacy, and Coram, CVS Specialty Infusion Services. Option Care has 162 in-person infusion centers located in 45 states. Option Care’s presence is highest in CA (24), FL (9), WA (9), OH (8), VA (8), and TX (7). UnitedHealth’s Optum Infusion Pharmacy has 30 in-person infusion suites located in 20 states, primarily concentrated in FL (6) and CA (4), but also provides home infusions in all 50 states. Like MHHI providers, neither of these alternate-site providers have locations in ND, SD, or WY. Coram announced a pilot with Cancer Treatment Centers of America in 2021 to provide home chemotherapy to patients in GA, but it is unclear if that pilot is ongoing; Coram provides home infusion therapy in 49 states. Conclusions: MHHI and alternate site infusion providers are in markets across the US. If alternate site chemotherapy infusion continues to grow, health system-owned and 3rd party entrant alternate site infusion providers are likely to prosper. Conversely, physician-owned practices could face competition and loss of important drug infusion revenue leading to increased consolidation among independent oncology providers. More research is needed to determine the impact on cost and patient outcomes of alternate site chemotherapy infusions – insights that will impact reimbursement and the rate at which these services continue to grow.

Enhanced gas separation performance of PIM-1 blend membranes incorporating ionic liquid (3-(trimethoxysilyl) propan-1-aminium acetate ([APTMS][Ac])) as filler: Investigation of morphology, compatibility and transport properties

Blend membranes were fabricated by incorporating an ionic liquid, 3-(trimethoxysilyl) propan-1-aminium acetate ([APTMS][Ac]), as a filler into the polymer of intrinsic microporosity PIM-1. The analyses using FTIR spectroscopy, AFM, and SEM confirmed a uniform dispersion and excellent polymer-filler compatibility, even at higher loadings. Gas transport properties were assessed with filler loadings up to 10 wt% of IL, revealing a slight reduction in permeability but an enhancement in selectivity. CO2 permeability of the blend membrane decreased by 37% at 10% filler loading, while the ideal selectivity increased from 19.6 to 29.0 for CO2/CH4 and from 20.9 to 31.7 for CO2/N2 upon increasing [APTMS][Ac] content (0 wt% − 10 wt%). The CO2/CH4 gas mixture selectivity rose by 58.62% and the CO2 permeability dropped by 40.44% compared to the pristine PIM-1 membrane. For the CO2/N2 gas mixture, the selectivity and CO2 permeability were enhanced by 40.11% and reduced by 39.07%, respectively. The permeability reduction can be ascribed to the filling of free volume voids in the PIM-1 polymer matrix by the IL [APTMS][Ac], while the selectivity improvement can be attributed to the strong interaction and high solubility of CO2 in the ionic liquid. The CO2 solubility coefficient increased with the rising IL concentration, indicating the high solubility of the IL in the polymer matrix.

Plasma C18:0-ceramide is a novel potential biomarker for disease severity in myasthenia gravis.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG-specific activities of daily living scale (MG-ADLs) and 15-item MG quality of Life (MG-QOL15). The concentrations of serum interleukin-1β (IL-1β), IL-6, IL-17A, and IL-21 were determined by enzyme-linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow-cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0-Cer, C18:0-Cer, and C24:0-Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0-Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0-Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0-Cer has the potential to be a novel biomarker for disease severity in MG.

Development of a Nonenzymatic Colorimetric Sensor for the Detection of Uric Acid Based on Ionic Liquid-Mediated Nickel Nanostructures.

Uric acid (UA) is a metabolic byproduct of purine nucleotides and is excreted as a urine component. Abnormalities in UA metabolism cause localized inflammation due to crystal deposition and can lead to various diseases. In the current study, we successfully fabricated a biosensor based on 1-H-3-methylimidazolium acetate (ionic liquid, IL)-capped nickel nanoparticles (NiNPs) for the detection of uric acid in test samples. The structures of IL-capped NiNPs and their precursors were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The IL-capped NiNPs possessed intrinsic peroxidase-like properties and displayed selective UA quenching after interacting with 3,3′,5,5′-tetramethylbenzidine (TMB) solution. Different parameters such as pH, time, IL, TMB, and UA concentration were optimized to obtain the best results for the proposed sensor. The UA biosensor shows good responses in the linear range from 1 × 10–8 to 2.40 × 10–6 M, with a lower limit of detection of 1.30 × 10–7 M, a limit of quantification of 4.3 × 10–7 M, and an R2 value of 0.9994. For the colorimetric detection of UA, the proposed sensor gave a short time response of 4 min at room temperature and pH 7.5. The proposed sensing probe detects UA in real serum samples and could be used as a selective sensor for UA in the real sample detection.

Gene Coexpression Connectivity Predicts Gene Targets Underlying High Ionic-Liquid Tolerance in Yarrowia lipolytica.

ABSTRACTMicrobial tolerance to organic solvents such as ionic liquids (ILs) is a robust phenotype beneficial for novel biotransformation. While most microbes become inhibited in 1% to 5% (vol/vol) IL (e.g., 1-ethyl-3-methylimidazolium acetate), we engineered a robust Yarrowia lipolytica strain (YlCW001) that tolerates a record high of 18% (vol/vol) IL via adaptive laboratory evolution. Yet, genotypes conferring high IL tolerance in YlCW001 remain to be discovered. In this study, we shed light on the underlying cellular processes that enable robust Y. lipolytica to thrive in inhibitory ILs. By using dynamic transcriptome sequencing (RNA-Seq) data, we introduced Gene Coexpression Connectivity (GeCCo) as a metric to discover genotypes conferring desirable phenotypes that might not be found by the conventional differential expression (DE) approaches. GeCCo selects genes based on their number of coexpressed genes in a subnetwork of upregulated genes by the target phenotype. We experimentally validated GeCCo by reverse engineering a high-IL-tolerance phenotype in wild-type Y. lipolytica. We found that gene targets selected by both DE and GeCCo exhibited the best statistical chance at increasing IL tolerance when individually overexpressed. Remarkably, the best combination of dual-overexpression genes was genes selected by GeCCo alone. This nonintuitive combination of genes, BRN1 and OYE2, is involved in guiding/regulating mitotic cell division, chromatin segregation/condensation, microtubule and cytoskeletal organization, and Golgi vesicle transport.IMPORTANCE Cellular robustness to cope with stressors is an important phenotype. Y. lipolytica is an industrial robust oleaginous yeast that has recently been discovered to tolerate record high concentrations of ILs, beneficial for novel biotransformation in organic solvents. However, genotypes that link to IL tolerance in Y. lipolytica are largely unknown. Due to the complex IL-tolerant phenotype, conventional gene discovery and validation based on differential gene expression approaches are time-consuming due to a large search space and might encounter a high false-discovery rate. Here, using the developed Gene Coexpression Connectivity (GeCCo) method, we identified and validated a subset of most promising gene targets conferring the IL-tolerant phenotypes and shed light on their potential mechanisms. We anticipate GeCCo being a useful method to discover the genotype-to-phenotype link.

Investigations on the role of ionic liquid on the physicochemical characteristics and toxicological consequences of liposomes

Effect of 1-butyl-3-methylimidazolium chloride ionic liquid ([bmim]Cl, IL) on the monolayer/bilayer of either soy-phosphatidylcholine (SPC) or hydrogenated soy-phosphatidylcholine (HSPC), in combination with 30 ​mol% cholesterol (Chol), were investigated. Impact of IL on monolayers were explored by measuring the surface pressure (π)-area (A) isotherm with a Langmuir-surface balance. Lift-off area (A0) of the monomolecular films gradually increased [A0(HSPC+IL) ​> ​A0(SPC+IL)], collapse pressures (πc) decreased and passed through minima [πc(HSPC+IL) ​> ​πc(SPC+IL)] with increasing IL concentration ([IL]). Minimum molecular area (Amin) increased monotonously and compression moduli (Cs−1) followed the sequence (HSPC+IL) ​> ​(SPC+IL) at a particular π with respect to [IL]. Dynamic light scattering studies were carried out to determine the hydrodynamic diameter (dh), zeta potential (Z.P.) and polydispersity index (PDI) values while fluorescence anisotropy studies, using 7-hydroxycoumarin and 1,6-diphenyl-1,3,5-hexatriene, could reveal the micro-viscosity of liposomes. Increased size and rigidity, induced by IL, suggest the formation of leak-proof, condensed liposomes. Disruption of vesicles induced by IL were observed from transmission electron microscopic (TEM) studies. IL induced disintegration of liposome and kinetics of subsequent formation of adsorbed monolayer were accomplished by surface pressure-time isotherms. IL-induced liposomes were substantially less toxic as revealed by MTT assay. These liposomes are considered to be safely used as effective and controlled drug delivery systems.

Ionic liquids as a tunable solvent and modifier for biocatalysis

ABSTRACT The use of biocompatible ionic liquids (bio-ILs) as a “green” solvent with uniquely tunable cations and anions, specific selectivity, and many other desirable physicochemical properties in biocatalysis has shown great promises to address many challenges. A plethora of studies have demonstrated ILs possess a range of exceptional capabilities in coordinating biocatalysis such as stabilizing enzyme structure, enhancing enzyme-substrate interaction, increasing substrate solubility and product separation/removal, and improving enzyme immobilization/recycling. Therefore, bio-ILs have been explored for biocatalysis in a wide range of homogenous as well as multiphasic systems including biphasic, multiphasic, microemulsion, and whole-cell systems. This review provides an overview of IL-enabled biocatalysis including enzymatic and whole-cell reactions in homogeneous and multiphasic systems. First, the properties of IL concentration, specific ion effect, pH, viscosity, alkyl chain length, hydrophobicity, and polarity on the structures and activities of enzymes are discussed together with characterization techniques to elucidate the mechanisms of IL-enzyme interactions. Second, while homogenous biocatalysis systems containing ILs are briefly introduced and summarized, particular attention is given to multiphasic systems. Furthermore, recent progress in using bio-ILs to modify emerging new enzyme carrier materials including carbonaceous and magnetic nanomaterials, gel microspheres, and membranes as well as their effect on increasing enzyme stability and recycling are highlighted. Finally, we provide our expert opinion for more innovative research in the field and future outlook for the industrial application of ILs in biocatalysis.

Efficient removal of metal ions from the ionic liquid aqueous solution by selective electrodialysis

In this work, due to the fact that the simulate spinning solution containing [Emim]Dep ILs, Mg2+, Ca2+, K+ and Na+, the selective electrodialysis (SED) method was chosen to achieve the separation of ILs and metal ions by the discrepancy of electrostatic action, pore size, hydration energy and etc. Various operating parameters, including the applied voltage drop, pH, ILs concentration, Mg2+/[Emim]+ ratio, type of anions (SO42- and Cl-) were investigated to evaluate the separation ability. What’s more, the separation mechanism of [Emim]+ and metal ions was revealed under different initial concentration of ILs. The critical aggregation concentration of ILs decreased with an increase in the concentration of Mg2+ ion. The transmembrane rate of monovalent ion ([Emim]+, K+ and Na+) was faster than that of divalent metal ions (Mg2+, Ca2+). In the natural spinning solution, PIL, RMg2+ and RCa2+ reached up to 90%, 98% and 96%, respectively. The spectra of FT-IR, 1H NMR and 13C NMR proved that the recycled ILs by the SED method was electrochemically stable. These results demonstrated that the SED process can be employed to separate the metal ions from the IL aqueous solution.

P221 DAPAGLIFLOZIN ASSOCIATED TO SACUBITRIL/VALSARTAN EXERTS ADDITIVE CARDIOPROTECTION IN HUMAN CARDIOMYOCYTES EXPOSED TO DOXORUBICIN AND TRASTUZUMAB THROUGH MYD88, NLRP3 MEDIATED PATHWAYS AND IMPROVEMENT OF MYTOGENESIS

Abstract Introduction The cumulative incidence of cardiac events in breast cancer patients treated with anthracycline and trastuzumab at 1 year after the diagnosis of cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose co–transporter 2 inhibitors showed measurable benefits in reduction of HF hospitalization and cardiovascular mortality. LCZ696 (neprilysin inhibitor + valsartan) as able to lower the risk of cardiovascular events in chronic heart failure. Purpose We hypothesize that dapagliflozin associated to LCZ696 could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab–induced cardiotoxicity Methods Human cardiomyocytes (HL–1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin (50 nM) or LCZ696 (at 100 mM) or both in combination for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of MDA– 4–HNE and Ca2+ were performed through spectrophotometric methods. Anti–inflammatory studies were also performed (expression of NLRP3, TLR4/MyD88 pathways, nuclear expression of NF–kB). Intracellular concentration of IL–1α, IL–1β, IL–2, IL–4, IL–6, IL–8, IL–10, IL–12, IL17–α, IL–18, IFN–γ, TNF–α, G–CSF, and GM–CSF were also performed. Results Dapagliflozin and LCZ696 increased synergistically the cell viability during exposure to doxorubicin and trastuzumab. Combination of dapagliflozin and LCZ696 reduces Ca2+ overload (–68,4% vs cells treated only to anticancer drugs; p < 0,001) and MDA (mean reduction of 57–63,4 % compared to cells exposed only to anticancer drugs; p < 0,05). The expression of MyD88, NLRP3 and NF–kB were strongly reduced after treatment with dapagliflozin and LCZ–696 (–52,5, –43,7 and –57,3 % vs cells exposed only to anticancer drugs, respectively; p < 0.05). Notably, combination of dapagliflozin and LCZ–696 enhanced the expression of IL–10. Expression of IL–1α, IL–1β, IL–6, IL–8, IL17–α and IL–18 was reduced (p < 0.05). Mitogenesis was strictly improved also as demonstrated by confocal microscope analysis Conclusion Dapagliflozin associated to LCZ–696 exerts additive cardioprotective and anti–inflammatory effects compared to each drug alone. Their properties are mediated by the reduction of iCa2+ content that consequently reduces peroxidation and NLRP3– MyD88 expression. These results indicating the potential use of SGLT–2 inhibitors associated to LCZ696 in preclinical models of cardiotoxicity.