Widening the stimuli-responsiveness of aqueous biphasic systems by changing the ionic liquid cation basicity.

Herein we demonstrate the formation of new stimuli-responsive aqueous biphasic systems (ABS), able to respond simultaneously to temperature and pH, or just to one stimulus, therefore allowing the design of more sustainable separation processes. This dual behavior is achieved with ABS formed by mono or dicationic protic ionic liquids as phase-forming components, being defined by the ionic liquid cation chemical structure or its basicity. While ABS comprising monocationic ionic liquids only respond to the effect of temperature, systems comprising dicationic ionic liquids are simultaneously affected by both temperature and pH variations. Dicationic ionic liquids are here identified as the key to unlock a double response to stimuli, which is due to the presence of two pKa values afforded by the cation. The reported findings contribute to increase the customizability of double stimuli-responsive ABS based on ionic liquids, whose development was up to date limited to ionic liquids bearing pH-responsive anions, opening the door towards the development of more sustainable separation processes.

Dynamic In Situ Monitoring of the Salt Counter-ion Effect on Surfactant Effectiveness Using Reconfigurable Janus Emulsions.

A straightforward method for visualization and quantification of surfactant effectiveness within different electrolyte environments based on using reconfigurable Janus emulsions as novel optical probes is reported. More specifically, we investigated the effect of different types and concentrations of salt counter-ions on the surfactant surface excess of commercial ionic and non-ionic surfactants, namely sodium dodecyl sulfate (SDS) and Tween 80 via in situ monitoring the morphological reconfigurations of biphasic Janus emulsions comprising hydrocarbon and fluorocarbon oils. We find that significant variations in interfacial tensions of SDS-stabilized interfaces (up to 15 mN·m-1) can be evoked by titrating mono-, di-, and trivalent cationic counter-ions, which is coherent with the lyotropic (Hofmeister) series. In contrast, the salt counter-ion effect on the surfactant effectiveness was less pronounced for the non-ionic surfactant Tween 80 (∼3 mN·m-1). Our results reveal a facile in situ method for monitoring the central role of electrolyte type and concentration on surfactant effectiveness and, more broadly, illustrate that Janus emulsions serve as powerful optical probes to dynamically study the properties of surfactants at liquid interfaces. We demonstrate the utility of our findings for an electro-induced morphological reconfiguration of Janus droplet morphologies by dynamically tuning Cu2+ concentration in solution using an electrode setup. The latter provides a unique platform for liquid-phase, real-time, and continuous tuning of Janus droplet morphologies, e.g., for their application in sensing and dynamic optical device platforms.

Effect of Zwitterionic Additive on Electrode Protection through Electrochemical Performances of Anatase TiO2 Nanotube Array Electrode in Ionic Liquid Electrolyte.

In this work, a functionalized zwitterionic (ZI) compound 1-butylsulfonate-3-methylimidazole (C1C4imSO3) was synthesized and tested as an additive to LiTFSI/C2C2imTFSI ionic liquid-based electrolytes for lithium-ion batteries. The structure and purity of C1C4imSO3 were confirmed by NMR and FTIR spectroscopy. The thermal stability of the pure C1C4imSO3 was examined by simultaneous thermogravimetric-mass spectrometric (TG-MS) measurements and differential scanning calorimetry (DSC). The LiTFSI/C2C2imTFSI/C1C4imSO3 system was tested as a potential electrolyte for lithium-ion batteries by using anatase TiO2 nanotube array electrode as the anode material. This electrolyte with 3% C1C4imSO3 showed significant improvement of lithium-ion intercalation/deintercalation properties, such as capacity retention and Coulombic efficiency compared to electrolyte without additive.

Solubility and Solvation Properties of Pharmaceutically Active Ionic Liquid Benzocainium Ibuprofenate in Natural Deep Eutectic Solvent Menthol-Lauric Acid.

Due to their appealing physiochemical properties, particularly in the pharmaceutical industry, deep eutectic solvents (DESs) and ionic liquids (ILs) are utilized in various research fields and industries. The presented research analyzes the thermodynamic properties of a deep eutectic solvent created from natural molecules, menthol and lauric acid in a 2:1 molar ratio, and an ionic liquid based on two active pharmaceutical ingredients, benzocainium ibuprofenate. Initially, the low solubility of benzocainium ibuprofenate in water was observed, and a hydrophobic natural deep eutectic mixture of menthol:lauric acid in a 2:1 ratio was prepared to improve benzocainium ibuprofenate solubility. In order to determine the solvent properties of DESs and ILs mixtures at different temperatures and their molecular interactions to enhance the solvent performance, the apparent molar volume, limiting apparent molar expansibility, and viscosity B coefficient were estimated in temperature range from 293.15 K to 313.15 K and varying concentration of benzocainium ibuprofenate.

Facile Monitoring of Water Hardness Levels Using Responsive Complex Emulsions.

The cationic content of water represents a major quality control parameter that needs to be followed by a rapid, on-site, and low-cost method. Herein, we report a novel method for a facile monitoring of the mineral content of drinking water by making use of responsive complex emulsions. The morphology of biphasic oil-in-water droplets solely depends on the balance of interfacial tensions, and we demonstrate that changes in the surfactant effectiveness, caused by variations in the mineral content inside the continuous phase, can be visualized by monitoring internal droplet shapes. An addition of metal cations can significantly influence the surfactant critical micelle concentrations and the surface excess values and therefore induce changes in the effectiveness of ionic surfactants, such as sodium dodecyl sulfate. The morphological response of Janus emulsions droplets was tracked via a simple microscopic setup. We observed that the extent of the droplet response was dependent on the salt concentration and valency, with divalent cations (responsive for water hardness), resulting in a more pronounced response. In this way, Ca2+ and Mg2+ levels could be quantitatively measured, which we showcased by determination of the mineral content of commercial water samples. The herein demonstrated device concept may provide a new alternative rapid monitoring of water hardness levels in a simple and cost-effective setup.

Correlation between biomarkers of creatine metabolism and serum indicators of peripheral muscle fatigue during exhaustive exercise in active men.

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 ± 3.7 years; VO2max 49.5 ± 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 ± 8.5%(95% CI, -0.4 to 11.0), and serum creatine elevated by 33.9 ± 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P ≤ 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.

Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study.

In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV-Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ±â€¯0.1) and (3.4 ±â€¯0.1) × 103 M-1, respectively], an intercalative mode also confirmed through viscosity measurements. Ka values, obtained as result of fluorescence titration of BSA with D13 and D15 [Ka = (4.2 ±â€¯0.2) and (2.6 ±â€¯0.2) × 105 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region.

Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels.

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography.

Serum creatine is not a reliable marker of muscular fitness in young adults.

PURPOSE: Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3 ± 2.6 years), while controlling for age, gender, fat-free mass and biomarkers of creatine metabolism as effect modifiers. MATERIALS AND METHODS: Serum creatine, creatinine and guanidinoacetic acid (GAA) levels were measured with liquid chromatography-tandem mass spectroscopy, while handgrip strength was assessed with a hydraulic hand dynamometer. RESULTS: Hierarchical multiple regression revealed that our model as a whole explained 79.9% of the variance in handgrip strength (p < 0.001). However, the evaluation of the contribution of each independent variable revealed that gender and free-fat mass make significant contributions (45.4 and 31.8%, respectively) to our model (p < 0.05), while neither age (0.9%) nor serum creatine (4.5%) or any other lab markers made significant contributions to the model (p > 0.05). CONCLUSIONS: Having higher blood creatine appears to be unrelated with better physical performance in young healthy adults. Serum creatine was not a reliable marker of muscular fitness in this population.

New sample preparation method based on task-specific ionic liquids for extraction and determination of copper in urine and wastewater.

In this study, four hydrophilic ionic liquids (ILs) containing 1-alkyl-3-methylimidazolim cation and either salicylate or chloride anions were synthetized and studied as new task-specific ionic liquids (TSILs) suitable for aqueous biphasic system (ABS) formation and selective one-step extraction of copper(II). TSILs are designed so that the anion is responsible for forming the complex with metal(II) and preventing hydrolysis of metal cations at very strong alkaline pH, whereas the cation is responsible for selective extraction of metal(II)-salicylate complexes. It was found that 1-butyl-3-methylimidazolium salicylate could be used for selective extraction of Cu(II) in the presence of Zn(II), Cd(II), and Pb(II) at very alkaline solution without metal hydroxide formation. It was assumed that formation of metal(II)-salicylate complexes prevents the hydrolysis of the metal ions in alkaline solutions. The determined stability constants for Cu(II)-salicylate complexes, where salicylate was derived from different ionic liquids, indicated that there was no significant influence of the cation of the ionic liquid on the stability of the complexes. The ABS based on 1-butyl-3-methylimidazolium salicylate has been applied as the sample preparation step prior to voltammetric determination of Cu(II). The effect of volume of aqueous sample and IL and extraction time were investigated and optimum extraction conditions were determined. The obtained detection limits were 8 ng dm-3. The optimized method was applied for the determination of Cu(II) in tap water, wastewater, and urine. The study indicated that application of the ABS based on 1-butyl-3-methylimidazolium salicylate ionic liquid could be successfully applied as the sample preparation method for the determination of Cu(II) from various environmental samples. Graphical abstract Aqueous biphasic system based on task-specific ionic liquid as a sample pretreatment for selective determination of Cu(II) in biological and environmental sample.

Biological evaluation of selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: Molecular docking study.

In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4-benzoxazin-2-ones. The results obtained showed that compounds 5, 9-11 have good cytotoxic activity against HeLa cells where the lowest IC50 value (10.46 ± 0.82 µM/mL) was measured for compound 10. Additionally, the most active compounds (5, 9-11) showed much better selectivity for MRC-5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α-glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54 ± 0.09 and 40.09 ± 0.49 µM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB-DNA complex through intercalation, suggesting good competition with EB (Ksv = (3.1 ± 0.2), (5.1 ± 0.1), (5.6 ± 0.2), and (6.3 ± 0.2) × 103 M-1 ). A molecular docking study was also performed to better understand the binding modes and to conclude the structure-activity relationships of the synthesized compounds.

Self-assembling, reactivity and molecular dynamics of fullerenol nanoparticles.

In this work structuring of water and insight into intermolecular interactions between water and fullerenol are studied throughout the process of forming nanoagglomerates at different temperatures applying both experimental and computational approaches. The obtained fullerenol nanoparticles (FNPs) are firstly characterized using dynamic light scattering, atomic force microscopy and transmission electron microscopy. The density, electrical conductivity and dynamic viscosity of aqueous fullerenol solutions are measured in the temperature range of 293.15 to 315.15 K. From the experimental density results other important thermodynamic values, such as apparent molar volumes and the partial molar volumes of water and fullerenol, are also calculated. To support the conclusion derived from the experimental density and calculated volumetric parameters, and to better understand the nature of the interactions with water, molecular dynamics simulations and radial distribution functions are also employed.

From Synthesis to Functionality: Tailored Ionic Liquid-Based Electrospun Fibers with Superior Antimicrobial Properties.

Herein, we report an efficient and facile strategy for the preparation of imidazolium-based ionic liquid (IL) monomers ([CnVIm][Br], n = 2, 4, 6, 8, 10, and 12) and their corresponding polymeric ionic liquids (PILs) with potent antimicrobial activities against Gram-negative and Gram-positive bacteria and fungi. The electrospinning technique was utilized to tailor the polymers with the highest antimicrobial potency into porous membranes that can be easily implemented into diverse systems and extend their practical bactericidal application. The antimicrobial mechanism of obtained ILs, polymers, and nanomaterials is considered concerning the bearing chain length, polymerization process, and applied processing technique that provides a unique fibrous structure. The structure composition was selected due to the well-established inherent amphiphilicity that 1-alkylimidazolium ILs possess, coupled with proven antimicrobial, antiseptic, and antifungal behavior. The customizable nature of ILs and PILs complemented with electrospinning is exploited for the development of innovative antimicrobial performances born from the intrinsic polymer itself, offering solutions to the increasing challenge of bacterial resistance. This study opens up new prospects toward designer membranes providing a complete route in their designing and revolutionizing the approach of fabricating multi-functional systems with tunable physicochemical, surface properties, and interesting morphology.

Electrolyte-induced aggregation of zein protein nanoparticles in aqueous dispersions.

Ion specific effects on the charging and aggregation features of zein nanoparticles (ZNP) were studied in aqueous suspensions by electrophoretic and time-resolved dynamic light scattering techniques. The influence of mono- and multivalent counterions on the colloidal stability was investigated for positively and negatively charged particles at pH values below and above the isoelectric point, respectively. The sequence of the destabilization power of monovalent salts followed the prediction of the indirect Hofmeister series for positively charged particles, while the direct Hofmeister series for negatively charged ones assumed a hydrophobic character for their surface. The multivalent ions destabilized the oppositely charged ZNPs more effectively and the aggregation process followed the Schulze-Hardy rule. For some multivalent ions, strong adsorption led to charge reversal resulting in restabilization of the suspensions. The experimental critical coagulation concentrations (CCCs) could be well-predicted with the theory developed by Derjaguin, Landau, Verwey and Overbeek indicating that the aggregation processes were mainly driven by electrical double layer repulsion and van der Waals attraction. The ion specific dependence of the CCCs is owing to the modification of the surface charge through ion adsorption at different extents. These results are crucial for drug delivery applications, where inorganic electrolytes are present in ZNP samples.

Enhancing Bioactivity of N,N,N-Chelating Rhodium(III) Complexes with Ionic Liquids: Toward Targeted Cancer Therapy.

This study investigates the potential of using ionic liquids as cosolvents to enhance the solubility and activity of poorly soluble rhodium(III) complexes, particularly those with diene, pyridine derivatives, and camphor-derived bis-pyrazolylpyridine ligands, in relation to 5'-GMP, CT-DNA, and HSA as well as their biological activity. Findings indicate that ionic liquids significantly increase the substitution activity of these complexes toward 5'-GMP while only marginally affecting DNA/HSA binding affinities with molecular docking, further confirming the experimental results. Lipophilicity assessments indicated good lipophilicity. Notably, cytotoxicity studies show that Rh2 is selectively effective against HeLa cancer cells, with IL1 and IL10 modulating the cytotoxic effects. Redox evaluations indicate that rhodium complexes induce oxidative stress in cancerous cells while maintaining redox balance in noncancerous cells. By elucidating the role of ionic liquids in modulating these effects, the study proposes a promising avenue for augmenting the efficacy and selectivity of cancer treatments, thus opening new horizons in cancer therapeutics.

Ibuprofen as an Organic Pollutant in the Danube and Effects on Aquatic Organisms.

The presence of emerging substances in surface water is of a great concern knowing they are the main source for community water supply needs. This study describes the development, optimization and application of an analytical method for the determination of ibuprofen in the Danube samples. Caffeine concentrations, as an indicator of human waste, were determined and maximum risk indexes for aquatic organisms were calculated. The Danube samples were collected from ten representative locations. A Solid-phase extraction was used for ibuprofen and caffeine separation and the analysis was performed by High-performance liquid chromatography method. Ibuprofen concentrations ranged (30.62-111.40) ng/L and caffeine (305.94-375.97) ng/L. Low risk on aquatic organisms was determined for ibuprofen and potential sublethal effect for caffeine was obtained. The results indicated that ibuprofen was effectively separated from other substances in the samples under defined chromatographic conditions for short period of time (4 minutes). Applied HPLC method showed good repeatability, accuracy, selectivity and robustness. Further studies including continuous monitoring of caffeine in the Danube are necessary in order to assess the real risks and possible prevention.

Application of biodegradable cholinium ionic liquids for the extraction of 5-hydroxymethylfurfural (HMF) from honey.

5-Hydroxymethylfurfural (HMF), a Maillard reaction product, can be formed when honey is subjected to heat treatment or a long storage time, becoming volatile and toxic depending on its concentration. The fact that, until today, there is no literature data on the extraction of 5-hydroxymethylfurfural (HMF) from honey using ionic liquids directed the investigation of the influence of biodegradable cholinium ionic liquids on the formation of aqueous biphasic systems and the application of these systems for the extraction of HMF from honey. The influence of anions of synthesised ionic liquids on the construction of biphasic systems in which an inorganic salt was used as a salting agent was investigated. Then, the extraction of HMF in these systems was examined, and the mechanisms of HMF extraction using ionic liquids were explained using computer simulations. Examining the effect of cholinium ionic liquids (choline chloride ([Ch][Cl]), cholinium nicotinate ([Ch][Nic]), cholinium propionate ([Ch][Prop]), and cholinium butyrate ([Ch][But])) on the formation of aqueous biphasic systems by comparing the phase diagrams, it was concluded that the ability of ionic liquids to form an aqueous biphasic system with tripotassium phosphate (K3PO4) decreases in the following order: [Ch][But] ≈ [Ch][Prop] > [Ch][Nic] > [Ch][Cl]. By applying all tested aqueous biphasic systems for the extraction of HMF from honey, an extraction efficiency of more than 89% was achieved. Complete extraction was achieved using the extraction system with [Ch][But], while the weakest ability to extract HMF was exhibited by the system with [Ch][Cl]. The mechanisms of HMF extraction using ionic liquids are explained on the basis of the optimised structures of the ionic liquid systems with HMF, together with the visualisation of non-covalent interactions, and on the basis of the calculated binding energies ΔGbin, which can be used as a good predictor of the extraction potential of newly synthesised ionic liquids.

Influence of side-chain length on antifungal efficacy of N-alkyl nicotinamide-based compounds.

This article presents fungicidal properties of 9 synthesized nicotinamide-bromides with different alkyl side chain lengths toward Fusarium graminearum, Sclerotinia sclerotiorum, and Botrytis cinerea which were examined. The fungicidal properties were determined by the measurement of the radial growth of fungi, followed by the calculation of the antifungal index. The obtained results were correlated with the descriptors from DFT calculations to determine structural features that affect the fungicidal properties of nicotinamides. Based on the experimental and theoretical results, it was confirmed that F. graminearum is most resistant to the change of lipophilicity of compounds, while S. sclerotiorum is most sensitive. For all investigated compounds, the growth rate decreased with the increase of carbon atoms in the side chain until tetradecylnicotinamidium bromide, [C14Nic][Br], while the further prolongation of the alkyl side chain increased the growth rate of fungus. This behavior was explained by the distinguished hydrophobic and hydrophilic surfaces in [C14Nic][Br] due to interactions between keto oxygen and bromide anion absent in the case of nicotinamides with a longer chain.

Influence of Sodium Salicylate on Self-Aggregation and Caffeine Solubility in Water-A New Hypothesis from Experimental and Computational Data.

The present study analyzed experimental data from volumetric and viscosimetric measurements and computational simulations to understand caffeine hydration and aggregation properties in 0.1 mol∙kg-1 of sodium salicylate aqueous solution. Sodium salicylate reduces the bitter taste and increases the solubility of caffeine in water, which is the main reason for their combination in food products. The results noted in volumetric and viscosimetric measurements indicate that sodium salicylate promotes the self-aggregation of caffeine in water. After self-aggregation, the hydration number of caffeine significantly increases. Molecular simulations have allowed us to hypothesize how salicylate increases caffeine solubility. At the molecular level, relocating salicylate moiety from the parallel stacking (π-π) aromatic complex with caffeine and its hydration could be the main reason for increasing the solubility of caffeine in water. The presented study provides clear guidelines on the choice of additives to increase caffeine's solubility in aqueous media. The choice of salicylate as an additive to increase the solubility of caffeine is very important because caffeine and salicylate are found in combination in a large number of formulations.