Solvent-free Liquid Research Articles

Ionic Liquids Immobilized Synthesis of New Xanthenes Derivatives and their Antiproliferative, Molecular Docking, and Morphological Studies.

Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry. This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents. The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 was used to synthesize new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst. Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions. The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.

Alkyl-π Functional Molecular Gels: Control of Elastic Modulus and Improvement of Electret Performance.

The development of optoelectronically-active soft materials is drawing attention to the application of soft electronics. A room-temperature solvent-free liquid obtained by modifying a π-conjugated moiety with flexible yet bulky alkyl chains is a promising functional soft material. Tuning the elastic modulus (G') is essential for employing optoelectronically-active alkyl-π liquids in deformable devices. However, the range of G' achieved through the molecular design of alkyl-π liquids is limited. We report herein a method for controlling G' of alkyl-π liquids by gelation. Adding 1 wt % low-molecular-weight gelator formed the alkyl-π functional molecular gel (FMG) and increased G' of alkyl-π liquids by up to seven orders of magnitude while retaining the optical properties. Because alkyl-π FMGs have functional π-moieties in the gel medium, this new class of gels has a much higher content of π-moieties of up to 59 wt % compared to conventional π-gels of only a few wt %. More importantly, the gel state has a 23 % higher charge-retention capacity than the liquid, providing better performance in deformable mechanoelectric generator-electret devices. The strategy used in this study is a novel approach for developing next-generation optoelectronically-active FMG materials.

Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS

BackgroundParallel artificial liquid membrane extraction (PALME) is a 96-well plate setup variant of liquid-phase microextraction. Basic or acidic analytes are extracted in neutral form from the sample, through a supported liquid membrane (SLM), and into aqueous acceptor. PALME is already considered a green extraction technique, but in the current conceptual work, we sought to make it even greener by replacing the use of organic solvents with essential oils (EO). PALME was combined with LC-MS/MS for analysis of plasma samples and multiple drugs of abuse with toxicological relevance (amphetamines, phenethylamines, synthetic cathinones, designer benzodiazepines, ayahuasca alkaloids, lysergic acid diethylamide, and ketamine). ResultsFourteen EO were compared to organic solvents frequently used in PALME. The EO termed smart & sassy yielded the best analyte recovery for all drugs studied and was thus selected as SLM. Then, factorial screening and Box-Behnken were employed to optimize the technique. The extraction time, concentration of base, sample volume, and percentage of trioctylamine significantly impacted analyte recovery. The optimum values were defined as 120 min, 10 mmol/L of NaOH, 150 μL, and 0%, respectively. Once optimized, validation parameters were 1–100 ng mL-1 as linear range, accuracy ±16.4%, precision >83%, 1 ng mL-1 as limit of quantitation, 0.1–0.75 ng mL-1 as limit of detection, matrix effect <20%, and recovery 20–106%. Additionally, EO purchased from different production batches were tested and achieved acceptable reproducibility. Data were in compliance with requirements set by internationally accepted validation guidelines and the applicability of the technique was proven using authentic samples. SignificanceIn this study, the use of an EO provided a solvent-free sample preparation technique suited to extract different classes of drugs of abuse from plasma samples, dismissing the use of hazardous organic solvents. The method also provided excellent sample clean-up, thus being a simple and efficient tool for toxicological applications that is in agreement with the principles of sustainable chemistry.

Luminescent solvent-free liquids based on Schiff-base boron difluoride complexes with polyethylene glycol chains.

A series of Schiff-base boron difluoride complexes with polyethylene glycol chains were synthesized and their photophysical properties were examined. These complexes maintained the solvent-free liquid state even at room temperature and their glass transition temperatures (Tg) were determined to be around -40 °C. The complexes showed blue to yellow luminescence under UV irradiation in the solvent-free liquid state with good emission quantum yields (Φ) of up to 0.26. The luminescence colour could also be tuned by dissolving organic dyes in the blue luminescent liquid sample. Density functional theory (DFT) and time-dependent (TD) DFT calculations were performed to further understand the photophysical properties.

Polymerizable Solvent-free Organic Liquids: A New Approach for Large Area Flexible and Foldable Luminescent Films.

The high demand for light-emitting and display devices made luminescent organic materials as attractive candidates. Solvent-free organic liquids are one of the promising emitters among them due to the salient features. However, the inherent limitations of forming sticky and noncurable surfaces must be addressed to become an alternate emitter for large-area device applications. Herein, we functionalized solvent-free organic liquids having monomeric emission in bulk with polymerizable groups to improve the processability. The polymerizable group on carbazole, naphthalene monoimide, and diketopyrrolopyrrole-based solvent-free liquid emitters enabled on-surface polymerization. These emitters alone and in combinations can be directly coated on a glass substrate without the help of solvents. Subsequent photo or thermal polymerization leads to stable, non-sticky, flexible, foldable, and free-standing large-area films with reasonably high quantum yield. Our demonstration of the tunable and white light-emitting films using polymerizable solvent-free liquids might be a potential candidate in flexible/foldable/stretchable electronics. The new concept of polymerizable liquid can be extended to other functional features suitable for futuristic applications.

A novel organic solvent-free method for manufacturing polyethersulfone hollow fiber membranes using melt extrusion

Hollow fiber membranes are traditionally manufactured using the spinning process, which takes advantage of the phase separation/inversion for the creation of a porous structure. In this work, the use of melt extrusion led to the fabrication of hollow fiber membranes without the use of organic solvents. Following post-treatment, the fabricated partially dense fibers are transformed into porous fibers. In detail, ternary blends of polyethersulfone/poly(ethylene glycol)/poly(N-vinyl pyrrolidone) (PESU/PEG/PVP) were developed by combining a solvent-free liquid mixture of PEG/PVP into PESU. Using a single screw extruder, this blend was melted and extruded using an annular slit nozzle where PEG functioned as a plasticizer, i.e., decreased processing temperatures, while PVP aided in retaining the hollow fiber geometry. These hollow fibers were comprised of uniformly closed pores, occurring due to the expansion and formation of bubbles of evaporating PEG nucleated by PVP during extrusion. By immersing these fibers into an aqueous solution of sodium hypochlorite (NaOCl), PEG and PVP were removed, which led to an open porous structure with pore sizes between 100 nm and 1 μm throughout the membrane. The outer surfaces of the hollow fibers were found to contain a higher PVP content than the inner surface. As PVP and PESU are miscible, i.e., blended in a single phase, treatment with NaOCl led to the creation of open pores on the outer surface with pore sizes between 10 and 150 nm, thus deeming the outer surface functional as a separation layer. The effect of blend composition, extrusion settings, and post-treatment parameters on membrane morphology, water flux, thermal characteristics, and tensile strength was studied, while after the modification, near-pristine PESU membranes were pursued. A water-flux of 28 L/h m2 bar and a molecular weight cut-off (MWCO) of 90%, 75%, and 40% for poly(ethylene oxide) of an average of 1000 kDa, 400 kDa, and 100 kDa molecular weight, respectively, proved that via extrusion it is possible to produce hollow fiber membranes for ultrafiltration without the use of organic solvents.

Thermally Activated Delayed Fluorescent Solvent-free Organic Liquid Hybrids for Tunable Emission Applications.

The synthetic feasibility and excellent luminescence features of organic molecules attracted much attention and were eventually found useful in lighting applications. In this context, a solvent-free organic liquid having attractive thermally activated delayed fluorescence features in bulk along with high processability has prime importance. Herein, we report a series of naphthalene monoimide-based solvent-free organic liquids exhibiting cyan to red thermally activated delayed fluorescence with luminescence quantum yields up to 80% and lifetimes between 10 to 45 µs. An effective approach explored energy transfer between liquid donors with various emitters exhibiting tunable emission colors, including white. The high processability of liquid emitters improved the compatibility with polylactic acid and was used for developing multicolor emissive objects using 3D printing. Our demonstration of the thermally activated delayed fluorescence liquid will be much appreciated as a processable alternate emissive material suitable for large-area lighting, display, and related applications.

Thermodynamic and kinetic aspects of the solvent-free liquid–liquid synthesis of tailor-made glyceride esters

Direct esterification between glycerol and carboxylic acids allows the design of different glycerides according to predetermined applications. Five carboxylic acids (caprylic, capric, lauric, stearic and oleic) which formed a bi-phasic system with glycerol were tested for esterification in a 1:1 M proportion. Two strategies were pursued: on one hand, homogeneous acid catalysis using sulfuric acid or p-toluenesulfonic acid at 100 °C and on the other hand, reactions catalyzed by immobilized lipase B from Candida antarctica at 65 °C. The selectivity and yield for MG was higher at lower temperature and with the use of the enzyme. Lauric acid was the carboxylic acid with the higher yield and selectivity to MG despite the catalyst used. The decrease in the mutual solubility between the carboxylic acid and glycerol seems to favor MG formation. The rate of reaction decreased with the increase in the molecular weight of the carboxylic acid used and the introduction of one unsaturation. From caprylic to lauric acid, the catalyst performance was: p-toluenesulfonic acid > lipase > sulfuric acid whereas for stearic and oleic acids the lipase was superior. Reactant accumulation at the interface is proposed to explain these results. The thermodynamic UNIFAC model was applied to calculate the initial activity coefficients and molar fractions in each phase. It was demonstrated that the thermodynamic activity of the species is a more convenient representation of the effective concentration for kinetic description of a liquid–liquid system. The equilibrium constant of lipase reaction was calculated with an expression based on the activity of compounds. The equilibrium constant for diglycerides formation decreased with the carbon chain length.

Solvent-free protic liquid enabling batteries operation at an ultra-wide temperature range

Nowadays, electrolytes for commercial batteries are mostly liquid solutions composed of solvent and salt to migrate the ions. However, solvents of the electrolyte bring several inherent limitations, either the electrochemical window, working temperature, volatility or flammability. Herein, we report polyphosphoric acid as a solvent-free protic liquid electrolyte, which excludes the demerits of solvent and exhibits unprecedented superiorities, including nonflammability, wider electrochemical stability window (>2.5 V) than aqueous electrolyte, low volatility and wide working temperature range (>400 °C). The proton conductive electrolyte enables MoO3/LiVPO4F rocking-chair battery to operate well in a wide temperature range from 0 °C to 250 °C and deliver a high power density of 4975 W kg−1 at a high temperature of 100 °C. The solvent-free electrolyte could provide a viable route for the stable and safe batteries working under harsh conditions, opening up a route towards designing wide-temperature electrolytes.

Superanionic Solvent-Free Liquid Enzymes Exhibit Enhanced Structures and Activities.

The surface of a carboxylate-enriched octuple mutant of Bacillus subtilis lipase A (8M) is chemically anionized to produce core (8M)-shell (cationic polymer surfactants) bionanoconjugates in protein liquid form, which are termed anion-type biofluids. The resultant lipase biofluids exhibit a 2.5-fold increase in hydrolytic activity when compared with analogous lipase biofluids based on anionic polymer surfactants. In addition, the applicability of the anion-type biofluid using Myoglobin (Mb) that is well studied in anion-type solvent-free liquid proteins is evaluated. Although anionization resulted in the complete unfolding of Mb, the active α-helix level is partially recovered in the anion-type biofluids, and the effect is accentuated in the cation-type Mb biofluids. These highly active anion-type solvent-free liquid enzymes exhibit increased thermal stability and provide a new direction in solvent-free liquid protein research.

Fluorescent DNA thermotropic liquid crystal showing thermostability and water-resistance

Solvent-free soft biomaterials with fluorescent property are highly attractive because of their wide prospective applications in bioimaging and anticounterfeiting. However, in solvent-free condition, developing soft fluorescent DNA materials is very challenging. In this study, a type of fluorescent solvent-free DNA thermotropic liquid crystal (DNA-TPEA) is developed via the electrostatic complexation of DNA and tetraphenylethene-containing ammonium surfactant TPEA. Under UV light, DNA-TPEA could give bright luminescence with good quantum yield, which has been tested as an anticounterfeiting labeling biomaterial working at high temperatures and in aqueous condition. An investigation on the photoluminescence lifetime of DNA-TPEA indicates that the TPEA molecules are in two different environments, and for which a working mechanism is illustrated. This work provides a new strategy for developing fluorescent biomaterials in solvent-free condition by fusing AIE surfactants and biomolecules together via electrostatic force, which gains synthetic convenience compared to the covalent modification of biomolecules with fluorescent proteins.

Emerging Developments on Nanocellulose as Liquid Crystals: A Biomimetic Approach.

Biomimetics is the field of obtaining ideas from nature that can be applied in science, engineering, and medicine. The usefulness of cellulose nanocrystals (CNC) and their excellent characteristics in biomimetic applications are exciting and promising areas of present and future research. CNCs are bio-based nanostructured material that can be isolated from several natural biomasses. The CNCs are one-dimensional with a high aspect ratio. They possess high crystalline order and high chirality when they are allowed to assemble in concentrated dispersions. Recent studies have demonstrated that CNCs possess remarkable optical and chemical properties that can be used to fabricate liquid crystals. Research is present in the early stage to develop CNC-based solvent-free liquid crystals that behave like both crystalline solids and liquids and exhibit the phenomenon of birefringence in anisotropic media. All these characteristics are beneficial for several biomimetic applications. Moreover, the films of CNC show the property of iridescent colors, making it suitable for photonic applications in various devices, such as electro-optical devices and flat panel displays.

Transforming Waste Clamshell into Highly Selective Nanostructured Catalysts for Solvent Free Liquid Phase Oxidation of Benzyl Alcohol

High yield production of benzaldehyde in the solvent-free oxidation of benzyl alcohol by using green catalysts is highly desirable. In this work, calcium hydroxide derived from waste clamshell was used as low-cost and environmentally friendly catalyst support (CaSUP) for Pd and V nanoparticles. The physicochemical properties of the catalysts were analyzed using X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) technique, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The catalytic oxidation of benzyl alcohol to benzaldehyde was studied in a liquid phase reaction by using H2O2 as an oxidizing agent. The effects of catalyst loading, the molar ratio of hydrogen peroxide to benzyl alcohol, temperature and reaction duration were investigated. In the optimized conditions, Pd nanoparticles supported on clamshell-derived supports displayed excellent catalytic conversion (88%) and selectivity to benzaldehyde (89%). Furthermore, the catalyst can be effectively reused without a significant loss in its activity and selectivity. The high yield and stability can be related to the structural and basic properties of the catalyst. These results provide important insights into the benzyl alcohol oxidation process for industrial applications.

Insights into substrate behavior in a solvent-free protein liquid to rationalize its reduced catalytic rate.

When proteins are engineered with a polymer surfactant coating on their surface, they can form a liquid phase by themselves, without the need for a solvent, such as, say, water. However, such solvent-free protein liquids (SFPL), despite their capability to function at temperatures above those in aqueous solutions, exhibit much reduced catalytic rates. A comprehensive understanding of the nature of substrates in such liquids is crucial to reason out the reduced catalytic activity of enzymes as SFPL media, and thus identify the means to improve the same. Employing atomistic molecular dynamics simulations of lipase A from Bacillus subtilis in its SFPL form, we demonstrate that at low concentrations, the substrate molecules are located mostly in the hydrophilic layer of the surfactant shell that ensheaths the enzyme; substrates in this SFPL are present in various conformations with similar propensities as in the aqueous solution. Slower translational diffusion and reorientational dynamics, as well as the reduced tendency of a substrate molecule to closely interact with the enzymes in the SFPL medium have been identified herein as the contributing factors for the reduced activity of enzymes in this hybrid liquid. At high concentrations of substrates corresponding to those used in in vitro experiments, the formation of an enzyme-substrate complex is observed. Microscopic insights reported here can aid in the choice of surfactants to improve the catalytic rate of enzymes in SFPL.

Molecular simulations explain the exceptional thermal stability, solvent tolerance and solubility of protein-polymer surfactant bioconjugates in ionic liquids.

Proteins complexed electrostatically with polymer surfactants constitute a viscous liquid by themselves, called the solvent-free protein liquid (SFPL). A solution of SFPL in a room temperature ionic liquid (PS-IL) offers the protein hyperthermal stability, higher solubility and greater IL tolerance. A generic understanding of these protein-polymer systems is obtained herein through extensive atomistic molecular dynamics simulations of three different enzymes (lipase A, lysozyme and myoglobin) under various conditions. Along with increased intra-protein hydrogen bonding, the surfactant coating around the proteins imparts greater thermal stability, and also aids in screening protein-IL interactions, endowing them IL tolerance. The reduced surface polarity of the protein-polymer bioconjugate and hydrogen bonding between the ethylene glycol groups of the surfactant and the IL cation contribute to the facile solvation of the protein in its PS-IL form. The results presented here rationalize several experimental observations and will aid in the improved design of such hybrid materials for sustainable catalysis.

Donor-acceptor based solvent-free organic liquid hybrids with exciplex emission and room temperature phosphorescence.

Solvent-free organic liquids are well-known for their excellent luminescence features. Hence, the recent developments in this area have marked them as potential emitters with high quantum yield and enhanced processability. The support of an available liquid matrix enables doping to deliver hybrid liquids with intriguing luminescence features. In this direction, we report solvent-free liquid donor-acceptor pairs with exciplex emission and room temperature phosphorescence at very low acceptor loading. The underlying weak intermolecular interactions have been revealed by 2D NMR techniques and theoretical calculations. The formation of large-area thin films by exciplex and phosphorescent liquid hybrids will encourage the development of scalable lighting and display materials.

Functionalization of Biphenylcarbazole (CBP) with Siloxane-Hybrid Chains for Solvent-Free Liquid Materials.

We report herein the synthesis of siloxane-functionalized CBP molecules (4,4′-bis(carbazole)-1,1′-biphenyl) for liquid optoelectronic applications. The room-temperature liquid state is obtained through a convenient functionalization of the molecules with heptamethyltrisiloxane chains via hydrosilylation of alkenyl spacers. The synthesis comprises screening of metal-catalyzed methodologies to introduce alkenyl linkers into carbazoles (Stille and Suzuki Miyaura cross-couplings), incorporate the alkenylcarbazoles to dihalobiphenyls (Ullmann coupling), and finally introduce the siloxane chains. The used conditions allowed the synthesis of the target compounds, despite the high reactivity of the alkenyl moieties bound to π-conjugated systems toward undesired side reactions such as polymerization, isomerization, and hydrogenation. The features of these solvent-free liquid CBP derivatives make them potentially interesting for fluidic optoelectronic applications.

Green Stability Indicating Organic Solvent-Free HPLC Determination of Remdesivir in Substances and Pharmaceutical Dosage Forms

A green liquid chromatographic method is considered in this work to minimize the environmental impact of waste solvents. One important principle is to replace or eliminate the use of hazardous organic solvents. Organic impurities in any active pharmaceutical ingredient could arise either during the process of its synthesis, or as degradation products developed throughout the shelf-life. Remdesivir (RDS) is an antiviral drug, approved by the US Food and Drug Adminstration (-FDA), to treat SARS-Cov-2 virus during its pandemic crisis. We studied the stability of remdesivir against several degradation pathways using the organic solvent-free liquid chromatographic technique. Separation was performed on RP-C18 stationary phase using mixed-micellar mobile phase composed of a mixture of 0.025 M Brij-35, 0.1 M sodium lauryl sulfate (SLS), and 0.02 M disodium hydrogen phosphate, adjusted to pH 6.0. The mobile phase flow rate was 1 mL min−1, and detection was carried out at a wavelength of 244 nm. We profiled the impurities that originated in mild to drastic degradation conditions. The method was then validated according to International Conference of Harmonization (ICH) guidelines within a linearity range of 5–100 μg mL−1 and applied successfully for the determination of the drug in its marketed dosage form. A brief comparison was established with reported chromatographic methods, including a greenness assessment on two new metrics (GAPI and AGREE). This study is the first to be reported as eco-friendly, solvent-free, and stability indicating LC methodology for RDS determination and impurity profiling.

Photoswitchable solvent-free DNA thermotropic liquid crystals toward self-erasable shape information recording biomaterials.

Soft thermotropic liquid crystals (TLCs) have advantages on processability and shape memory compared to hard solids and fluids. The development of photoswitchable soft TLCs based on biomolecules would afford reworkable shape information recording biomaterials for the areas requiring biocompatibility and degradability. In recent years, anhydrous DNA TLCs composed of DNA and ammonium surfactants have been receiving continuous attention. However, the photoswitchable phase transition has not been realized for soft DNA TLCs at room temperature, owing to the absence of functional ammonium surfactant. Herein, a new type of azobenzene-containing surfactant would be applied to the fabrication of soft DNA TLCs with photoresponsive physical properties. The double-chain design of the used surfactant and the use of DOAB as a dopant guarantee the soft state of DNA TLCs at r.t., which also facilitates the azobenzene isomerization by reducing the packing density of surfactants. With the assistance of photoisomerization of azobenzene, the reported DNA TLCs achieve reversible liquid crystal-isotropic liquid transition at temperatures below clearing points even at room temperature. The repeatable shape information recording and self-erasing tests indicate these DNA TLCs would be good shape information recording biomaterials in the future. This work also provides a useful strategy for designing photoresponsive soft biomaterials based on rigid biomolecules like DNA.

Organic solvent-free elevated temperature liquid–liquid extraction combined with a new switchable deep eutectic solvent-based dispersive liquid–liquid microextraction of three phenolic antioxidants from oil samples

An organic solvent-free extraction procedure using elevated temperature liquid–liquid extraction/ dispersive liquid–liquid microextraction based on deep eutectic solvent has been performed for the extraction of three synthetic phenolic antioxidants from oil samples. In the developed approach, firstly the antioxidants were extracted into an aqueous alkaline solution in an elevated temperature. Then, a few microliters of deep eutectic solvent formed from tetrabutylammonium chloride and hydroquinone was dissolved in the alkaline solution and a homogenous solution was obtained. In the following it was dispersed into an acidic solution. In this step, an acid–base reaction was occurred and the analytes were migrated into the fine droplets of the deep eutectic solvent. The extracted analytes were determined by gas chromatography-flame ionization detector. Validation data showed that low limits of detection (0.13–0.42 ng/mL) and quantification (0.36–1.41 ng/mL), high extraction recovery (74–89%) and enrichment factor (370–445), and good precision (relative standard deviation ≤ 7.4%) can be obtained by the developed method. Finally, the method was used for quantification of the antioxidants in several edible oil samples.