Deep Eutectic System Research Articles

From a eutectic mixture to a deep eutectic system via anion selection: Glutaric acid + tetraethylammonium halides.

In pursuit of understanding structure-property relationships for the melting point depression of binary eutectic mixtures, the influence of the anion on the solid-liquid (S-L) phase behavior was explored for mixtures of glutaric acid + tetraethylammonium chloride, bromide, and iodide. A detailed experimental evaluation of the S-L phase behavior revealed that the eutectic point is shifted toward lower temperatures and higher salt contents upon decreasing the ionic radius. The salt fusion properties were experimentally inaccessible owing to thermal decomposition. The data were inter- and extrapolated using various models for the Gibbs energy of mixing fitted to the glutaric-acid rich side only, which allowed for the assessment of the eutectic point. Fitting the experimental data to a two-parameter Redlich-Kister expansion with Flory entropy, the eutectic depth could be related to the ionic radius of the anion. The anion type, and in particular its size, can therefore be viewed as an important design parameter for the liquid window of other acid and salt-based deep eutectic solvents/systems.

Lipase-Catalyzed Production of Sorbitol Laurate in a "2-in-1" Deep Eutectic System: Factors Affecting the Synthesis and Scalability.

Surfactants, such as glycolipids, are specialty compounds that can be encountered daily in cleaning agents, pharmaceuticals or even in food. Due to their wide range of applications and, more notably, their presence in hygiene products, the demand is continuously increasing worldwide. The established chemical synthesis of glycolipids presents several disadvantages, such as lack of specificity and selectivity. Moreover, the solubility of polyols, such as sugars or sugar alcohols, in organic solvents is rather low. The enzymatic synthesis of these compounds is, however, possible in nearly water-free media using inexpensive and renewable building blocks. Using lipases, ester formation can be achieved under mild conditions. We propose, herein, a “2-in-1” system that overcomes solubility problems, as a Deep Eutectic System (DES) made of sorbitol and choline chloride replaces either a purely organic or aqueous medium. For the first time, 16 commercially available lipase formulations were compared, and the factors affecting the conversion were investigated to optimize this process, owing to a newly developed High-Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) method for quantification. Thus, using 50 g/L of lipase formulation Novozym 435® at 50 °C, the optimized synthesis of sorbitol laurate (SL) allowed to achieve 28% molar conversion of 0.5 M of vinyl laurate to its sugar alcohol monoester when the DES contained 5 wt.% water. After 48h, the de novo synthesized glycolipid was separated from the media by liquid–liquid extraction, purified by flash-chromatography and characterized thoroughly by one- and two-dimensional Nuclear Magnetic Resonance (NMR) experiments combined to Mass Spectrometry (MS). In completion, we provide initial proof of scalability for this process. Using a 2.5 L stirred tank reactor (STR) allowed a batch production reaching 25 g/L in a highly viscous two-phase system.

Improved storage of influenza HA-VLPs using a trehalose-glycerol natural deep eutectic solvent system

Vaccines are typically stored under refrigerated conditions (2–8 °C) to limit potency and efficacy loss. Maintaining the cold chain is costly and prone to vaccine wastage due to unexpected changes in the storage conditions. The development of formulations conferring enhanced stability can extend vaccine shelf-life and facilitate storage under non-refrigerated conditions, thus simplifying the distribution process and reducing vaccine wastage. In this study, the suitability of a natural deep eutectic system (NADES) consisting of trehalose and glycerol (TGly) for storage of influenza hemagglutinin (HA)-displaying virus-like particles (VLPs) was successfully demonstrated. TGly was efficient in maintaining the activity and physical integrity of HA-VLPs for up to 4 h at 50 °C (accelerated stability study), with half-life values ≈ 20–34 h for the best TGly formulations. Importantly, improved storage is achieved at increasingly higher TGly concentrations, hence confirming the importance of TGly content in its protective capacity. In addition, HA-VLPs were stable in TGly for over one month at room temperature (short-term stability study), with no impact on HA titer or particle size distribution. This work highlights the potential of NADES to improve stability of VLP-based vaccines, showing promising protective capacity under non-refrigerated conditions and short-term thermal stress, and thus having a notable impact on vaccine’s cold chain.

Removal process and mechanism of lead in Zn-containing rotary hearth furnace dust

To deal with the removal of PbO2 during the purification process of the Zn-containing rotary hearth furnace (RHF) dust, this study adopts a choline chloride-urea (ChCl-urea) based deep eutectic solvent system and water-washed Zn-containing RHF dust as the main target of investigations, preparing ZnO nanoparticles using a Zn-induced PbO2 removal and thermal treatment of the precursor. The effects of the mass ratio of Zn particles and Zn dust (maked as Zn particles - Zn dust), reaction temperature, and reaction time on the removal of PbO2 were also investigated. The ZnO nanoparticles and the PbO2-removed products were characterized by X-ray diffractometry, X-ray fluorescence spectroscopy, scanning and transmission electron microscopy. The results showed that the optimal conditions for efficient removal of PbO2 included the reaction temperature of 80 °C, The Zn particles - Zn dust is 1.6, with a reaction time of 3 h. The final product had a ZnO content of 98.332% with a particle size distribution in the range of 10–100 nm with an average diameter of 39 nm, belonging to the Category-II ZnO nanoparticles. The PbO2 removal mechanism mainly involved the dissolving of PbO2 in ChCl-urea, forming [Pb(ClO·urea)2]2−, and the replacement reaction between Zn particles and [Pb(ClO·urea)2]2−, producing metallic Pb and [ZnClO·urea]−.

Experimental study on ethylene glycol/choline chloride deep eutectic solvent system based nanofluids

With the continuing development in the electric industry, highly efficient heat dissipation is of great significance due to the shrinkage of electric elements and increase in energy input. Working fluid, acting as a heat transfer medium, plays a core role in the thermal management. While, traditionally used working fluids suffer from either low thermal conductivity or relatively narrow liquid range that are unable to meet the growing demands for highly efficient thermal management. In this work, a silica decorated graphene (SDG) was fabricated using a sol-gel method and dispersed in a deep eutectic solvent (DES) system with the aim at addressing the poor thermal conductivity, stability and narrow working temperature range simultaneously. It is verified that the stability of nanofluids can be significantly improved since it could be kept for one week without obvious precipitation and aggregation due to the presence of silica coating on the layer of graphene. On the other hand, an 11.26% thermal conductivity enhancement was obtained by filling only 3.0 wt.% of the SDG. Moreover, viscosity study reveals that the presence of SDG has a slight influence on the rheological property of the nanofluids.

The construction of a new deep eutectic solvents system based on choline chloride and butanediol: The influence of the hydroxyl position of butanediol on the structure of deep eutectic solvent and supercapacitor performance

The precise regulation of the deep eutectic solvents (DESs) system has an important influence on its structure, performance and application. In this work, choline chloride (ChCl) and three kinds of butanediols are used as hydrogen bond acceptors and donors, respectively. The research focuses on the influence of two hydroxyl positions in butanediols on the structure and properties of DES systems with various characterization techniques. The results show that the DES system composed of 1, 2-butanediol and ChCl (the distance of two hydroxyl group is closest) possesses the largest conductivity (1.26 mS cm−1) and the lowest viscosity (56.99 cP). Moreover, using ChCl and 1, 2-butanediol as the electrolyte, the corresponding voltage of activated carbon (AC) based supercapacitor can reach 2 V, the specific capacitance can reach 116 F g−1 and the highest energy density is 16.14 Wh kg−1. More importantly, this work uses the DFT model to design and verify the DES systems in detail, and then explain the mechanism of the influence of the hydroxyl position on the structure and electrochemical performance of the DES system from a theoretical perspective. Obviously, the DES systems having difference structures and DFT calculation proposed in this article provide a significant way and reference for in-depth understanding of DES electrolytes and applications.

Generation of highly amenable cellulose-I\u03b2 via selective delignification of rice straw using a reusable cyclic ether-assisted deep eutectic solvent system

Cellulolytic enzymes can readily access the cellulosic component of lignocellulosic biomass after the removal of lignin during biomass pretreatment. The enzymatic hydrolysis of cellulose is necessary for generating monomeric sugars, which are then fermented into ethanol. In our study, a combination of a deep eutectic (DE) mixture (of 2-aminoethanol and tetra-n-butyl ammonium bromide) and a cyclic ether (tetrahydrofuran) was used for selective delignification of rice straw (RS) under mild conditions (100 °C). Pretreatment with DE-THF solvent system caused ~ 46% delignification whereas cellulose (~ 91%) and hemicellulose (~ 67%) recoveries remained higher. The new solvent system could be reused upto 10 subsequent cycles with the same effectivity. Interestingly, the DE-THF pretreated cellulose showed remarkable enzymatic hydrolysability, despite an increase in its crystallinity to 72.3%. Contrary to conventional pretreatments, we report for the first time that the enzymatic hydrolysis of pretreated cellulose is enhanced by the removal of lignin during DE-THF pretreatment, notwithstanding an increase in its crystallinity. The current study paves way for the development of newer strategies for biomass depolymerization with DES based solvents.

Efficient Purification of R-phycoerythrin from Marine Algae (Porphyra yezoensis) Based on a Deep Eutectic Solvents Aqueous Two-Phase System

R-phycoerythrin (R-PE), a marine bioactive protein, is abundant in Porphyra yezoensis with high protein content. In this study, R-PE was purified using a deep eutectic solvents aqueous two-phase system (DES-ATPS), combined with ammonium sulphate precipitation, and characterized by certain techniques. Firstly, choline chloride-urea (ChCl-U) was selected as the suitable DES to form ATPS for R-PE extraction. Then, single-factor experiments were conducted: the purity (A565/A280) of R-PE was 3.825, and the yield was 69.99% (w/w) under optimal conditions (adding 0.040 mg R-PE to ChCl-U (0.35 g)/K2HPO4 (0.8 g/mL, 0.5 mL) and extracting for 20 min). The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results revealed that the purified R-PE contained three main bands. One band was presented after purification in native-PAGE. The UV-vis spectra showed characteristic absorption peaks at 495, 540, and 565 nm. R-PE displayed an emission wavelength at 570 nm when excited at 495 nm. All spectra results illustrated that the structure of R-PE remained unchanged throughout the process, proving the effectiveness of this method. Transmission electron microscope (TEM) showed that aggregation and surrounding phenomena were the driving forces for R-PE extraction. This study could provide a green and simple purification method of R-PE in drug development.

Development of Polycaprolactone-Based metronidazole matrices for intravaginal extended drug delivery using a mechanochemically prepared therapeutic deep eutectic system.

The engineering of crystalline multi-component drug systems, including cocrystals and salts, is now an established method of modifying the physicochemical properties and dissolution behaviour of an active ingredient. Remarkably, liquid drug systems, including therapeutic ionic liquids and therapeutic deep eutectic solvents (THEDES), remain largely unexplored as an untapped reservoir for drug modification. In this work, the formation of a THEDES containing metronidazole (MET), the preferred first-line treatment for bacterial vaginosis (BV), was explored. The formed THEDES was evaluated for its dissolution behaviour from a simple polycaprolactone (PCL) matrix, in order to achieve an extended release, balanced with an appropriate onset of action, hence offering improved MET intravaginal application. To minimise handling of the liquid THEDES, an end-to-end continuous process that enables feeding of the raw materials in their respective solid forms, and collection of a solidified final formulation is presented. The concurrent THEDES formation and formulation were carried out using a bench scale (approx. 10g) twin-screw hot melt extruder. The chosen parent reagents have shown sufficiently strong reactivity and resulted in successful and complete conversion to THEDES while in the presence of PCL, during the extrusion process. The formulated THEDES-PCL matrix exhibited significantly improved onset of drug release followed by a controlled delivery of MET over a total 7-day period in SVF, proving itself as a viable alternative to oral therapy.

Choline chloride/pentaerythritol: a deep eutectic solvent for the synthesis of pyran and chromene derivatives

A novel deep eutectic solvent system was prepared by mixing choline chloride as a hydrogen-bond acceptor with 2,2-bis(hydroxymethyl)propane-1,3-diol (pentaerythritol) as a hydrogen-bond donor. This green solvent was used for the one-pot synthesis of pyran and chromene derivatives from aromatic aldehydes, 1,3-dicarbonyl compounds, and malononitrile. The solvent was readily recycled and can be reused three times without significant loss of activity or mass. This procedure offers advantages such as environmental friendliness, shorter reaction times, and higher yields.

A review on solvent systems for furfural production from lignocellulosic biomass

Utilizing biomass in biorefineries is a favorable sustainable method to produce platform chemicals, materials and energy. Conversions of lignocellulosic biomass to chemicals have greatly attracted attention recently due to its abundance in nature and high availability at low costs. The potential of lignocellulosic biomass lies in its ability to be transformed to clean energy, biochemical and industrial products. Furfural has been identified as a valuable platform chemical that can be derived from lignocellulosic biomass. Furfural could also be regarded as sustainable alternatives to petrochemical products. Currently, more than 80 furfural-derived chemicals are used in various industries. The main aim of this review was to discuss various solvent systems that emerged for furfural production from lignocellulosic biomass. Conventionally, furfural is produced by reactions in aqueous systems employing H2SO4 as the catalyst. In an effort to improve furfural production, various solvent systems started to emerge, namely organic solvent system, biphasic system, ionic liquid system, and deep eutectic solvent system. Advantages and limitations of each solvent system were discussed herein. In this review, the background of furfural and its reaction pathways were also discussed. Moreover, opportunities, challenges and limitations to advance furfural production in biorefineries were addressed in this review as well.

Synthesis cyclic carbonates with BmimCl-based ternary deep eutectic solvents system

A novel 1-Butyl-3-methylimidazolium chloride (BmimCl)-based ternary deep eutectic solvents system was developed and employed to convert CO2 into cyclic carbonates under mild conditions. Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), thermogravimetric and differential thermal analyses (TG-DTA) were used to character the DESs. Besides, the impacts of reaction parameters and substrate ranges on cycloaddition reaction were also investigated. Under the optimized reaction conditions, the yield of propylene carbonate (PC) was about 98.0 % over BmimCl/Boric acid (BA)/Glutaric acid (GA) (7/1/1, molar ratio). In addition, the BmimCl-based ternary DESs are easy to recycle and indicates excellent reusability. The mechanism of epoxide activated by hydrogen bonds and epoxide ring opening was proposed. The BmimCl-based ternary DESs will be viewed as an innovative system for cycloaddition of CO2 with epoxides and it will supply a novel class of DESs for other possible applications.

Enzymatic hydrolysis and extraction of ginsenoside recovered from deep eutectic solvent-salt aqueous two-phase system

Rare ginsenoside CK was recognized as a popular functional food because of superior pharmacological activity, but it is restricted by further applications by the difficulty in preparation. In this study, deep eutectic solvent (DES)-based aqueous two-phase system (ATPS) was established to transform and extract ginsenoside CK in situ for the first time. The phase formation conditions for preparing ATPS using choline chloride-based DES were studied, and the optimal conditions for extractive bioconversion were explored using conventional single-factor experiments. The conditions for ATPS establishment were as follows: 31.9% (w/w) DES (ChCl-ethylene glycol)/24.5% (w/w) K2HPO4, 55°C, pH 5.0. Under the optimal conditions, 75.79% product and 61.14% β-glucosidase were recovered from the top and bottom phase, respectively. In addition, DES and β-glucosidase can be recovered and recycled again for the next extractive bioconversion of CK. These results indicated that this green and efficient method exhibited considerable value in integrated production and extraction processes, and demonstrated the potential for obtaining highly recycled functional foods and similar products.

Synergistic Catalytic Synthesis of Gemini Lipoamino Acids Based on Multiple Hydrogen-Bonding Interactions in Natural Deep Eutectic Solvents-Enzyme System.

In the previous studies, gemini lipoamino acids (GLAA) were always synthesized by complex multistep organic synthesis, which involved a large number of byproducts and organic solvents. To develop a straightforward, efficient, and renewable synthesis strategy for GLAA, in this study, a type of novel green solvents, natural deep eutectic solvents (NADESs), were adopted as the solvents for these reactions. Five commercial enzymes were involved in the enzyme screening section, and Candida antarctica lipase B (CALB) tended to have the best performance in NADESs systems. The optimization procedure was performed using the Taguchi crossed array method and the highest yield of GLAA (59.14 ± 0.51%) was obtained in choline chloride-glycerol (C-Gly). The purification procedure was carried out with ethyl acetate and water, and the isolate yield ranged from 86.31 ± 2.36 to 91.34 ± 2.26%. With 10 times recycling, the yield of GLAA in C-Gly decreased from 59.14 ± 0.51 to 51.31 ± 0.68%. Interestingly, a synergistic effect of CALB and NADESs was found in the enzymatic synthesis of GLAA, which can be attributed to fatty acids being activated by chloride ions via hydrogen-bonding interactions and resulting in an enhancement in its electron-attracting ability.

Catalytic conversion of fructose into 5-HMF under eco-friendly-biphasic process

One-pot conversion of fructose into valuable 5-hydroxymethyl-2-furaldehyde (5-HMF) was investigated under a deep eutectic solvent-biphasic system.

Thermal Properties of Choline Chloride/Urea System Studied under Moisture-Free Atmosphere

Physical chemistry of an archetypal deep eutectic solvent system, choline chloride/urea, was studied using dry components under moisture-free conditions. The phase diagram reveals that the eutectic...

Recyclable menthol-based deep eutectic solvent micellar system for extracting phytochemicals from Ginkgo biloba leaves

Abstract With an emphasis on human health, the demand for natural products is progressively increasing and sustainable extraction technologies for phytochemicals are receiving greater attention. In the present study, we established a naturally recyclable two-phase aqueous micellar system comprising menthol-based hydrophobic deep eutectic solvent (DES) in water. Typical representative phytochemicals from Ginkgo biloba leaves included flavonoid glycosides, terpene lactones, and bioflavonoids. These compounds have differing polarities and were selected as targets for the evaluation of our novel menthol-based aqueous DES as a green and sustainable extraction technology for partitioning various compounds. Components of the aqueous DES system and extraction process were systematically studied, and the following optimal conditions were identified: menthol–acetic acid ratio of 1:1 (mol/mol), DES–water ratio of 1:1 (v/v), solid–liquid ratio of 15:1 (mg/mL), extraction power of 200 W, and extraction time of 10 min. The two-phase system easily separated compounds with differing polarity into the upper (DES-rich phase) and lower (water phase) phases after extraction. Analyses of the related mechanisms indicated that micelle formation of menthol-based DES in water was the dominant separating process and that this process provided large contact areas between target compounds and extraction solvent, thereby promoting extraction from G. biloba leaves. Moreover, this aqueous DES system could efficiently be recovered and reused in regeneration studies. This novel menthol-based aqueous DES system provides a sustainable extraction technology for various phytochemicals from plant materials.

Enzymatic glycolipid surfactant synthesis from renewables

Glycolipids are promising nonionic biosurfactants with a wide range of application. In contrast to the traditional surfactants from fossil origin, they are not only exhibiting excellent surfactant and emulsifying properties but are in addition biodegradable and non-toxic to the environment. Glycolipids can be produced by microbial fermentation, by chemical or enzymatical synthesis using renewable resources. In this review, strengths and weaknesses of each production method are compared and enzymatic synthesis is highlighted as the method of choice for the tailor-made synthesis of a wide range of novel glycolipids. As for enzymatical and chemical synthesis solvents with low water activity are needed to favor condensation instead of the hydrolysis reaction, organic solvents or ionic liquids are commonly used. However, the unusual deep eutectic solvent system might be a green alternative worth to consider. In terms of enzymatic catalysis, lipases are well known in literature and already widely used for the production of sugar-acyl-esters. However, β-glucosidases can be alternatively used for glycolipid synthesis which is far less studied. The abilities of both enzymes for glycolipid synthesis are therefore compared and discussed.

Therapeutic deep eutectic system of capric acid and menthol: Characterization and pharmaceutical application

The work outlined herein describes an evaluation of a new green solvent working as a drug solubility enhancer made up of a eutectic system comprising mixtures of capric acid and menthol. Fluconazole and mometasone furoate were tested as two common model drugs. The system suitability in enhancing drug solubility was carried out at three different capric acid: menthol mass ratios of 4:1, 1:1, and 1:4. Characterizing the phase forming mechanics involved in drug-related solubility was illustrated in this work by investigating the surface tension, contact angle, and viscosity of the mixtures at the same aforementioned capric acid: menthol ratios. Moreover, system compatibility with the two model drugs was given considerable attention using DSC and FTIR analysis. The system exhibited a decrease in surface tension (30–60%) and viscosity (30–70%) from initial values compared to common strong solvents in addition to a high wettability as indicated by low values of contact angles (<24 ⁰). Results further confirmed the effectiveness of the eutectic mixture in enhancing drug solubility. A cream preparation comprising the two drugs and their eutectic solvent constituents was evaluated for any acute skin irritation/erosion effect on Albino rabbits.

Air Assisted Dispersive Liquid–Liquid Microextraction (AA-DLLME) Using Hydrophilic–Hydrophobic Deep Eutectic Solvents for the Isolation of Monosaccharides and Amino Acids from Kelp

Air assisted dispersive liquid–liquid microextraction (AA-DLLME) using hydrophilic–hydrophobic deep eutectic solvents (DES) was developed for the simultaneous isolation of monosaccharides and amino acids with wide ranges of polarities from kelp using high performance liquid chromatography (HPLC). A response surface methodology (RSM) on a Box–Behnken design (BBD) model was employed to identify the optimal extraction parameters. Air assisted dispersive liquid-phase microextraction performed using the optimum deep eutectic solvent system, five push–pull cycles, a ratio of solid to liquid equal to 3 mg·mL−1, 10% (w/v) NaCl, and a centrifugation time of 6 min provided the best analytical performance. The optimal extracted concentrations of d-(+)-galactose, l-(-)-fucose, dl-tyrosine, and dl-valine in kelp were 16.7 ± 0.2, 8.6 ± 0.2, 2.6 ± 0.1, and 1.6 ± 0.1 mg·g−1, respectively. The method recoveries for d-(+)-galactose, l-(-)-fucose, dl-tyrosine, and dl-tyrosine were from 87 to 102%, 84 to 103%, 87 to 104%, and 85 to 103%. The relative standard deviations (RSDs) (n = 4) for the intra-day and inter-day determinations were <6.17%.