Use Of Natural Deep Eutectic Solvents Research Articles

Natural Deep Eutectic Solvents for the Extraction of Spilanthol from Acmella oleracea (L.) R.K.Jansen.

With a growing focus on green chemistry, the extraction of natural products with natural deep eutectic solvents (NADES), which are eutectic mixtures of hydrogen bond donors and acceptors, has become an ever-expanding field of research. However, the use of NADES for the extraction of spilanthol from Acmella oleracea (L.) R.K.Jansen has not yet been investigated. Therefore, in this study, 20 choline chloride-based NADES, and for comparison, ethanol, were used as green extraction agents for spilanthol from Acmella oleracea flower heads. The effects of time, water addition, and temperature on NADES extractions were investigated and analysed by HPLC-DAD quantification. Additionally, UHPLC-DAD-ESI-MSn results for dichloromethane extracts, as well as the isolation of spilanthol and other main constituents as reference compounds, are reported. The best green extraction results were achieved by choline chloride (ChCl) with 1,2-propanediol (P, 1:2 molar ratio, +20% water) at 244.58 µg/mL, comparable to yields with ethanol (245.93 µg/mL). Methylurea (MeU, 1:2, +20% water) also showed promising results as a hydrogen bond donor in combination with choline chloride (208.12 µg/mL). In further experiments with NADES ChCl/P (1:2) and ChCl/MeU (1:2), extraction time had the least effect on spilanthol extraction with NADES, while yield decreased with water addition over 20% and increased with extraction temperature up to 80 °C. NADES are promising extraction agents for the extraction of spilanthol, and these findings could lead to applicable extracts for medicinal purposes, due to their non-toxic constituents.

A novel strategy for extraction of intracellular poly(3-hydroxybutyrate) from engineered Pseudomonas putida using deep eutectic solvents: Comparison with traditional biobased organic solvents

Polyhydroxyalkanoates (PHAs) represent a category of microbial polyesters that offer both biodegradability and biocompatibility, if produced in sufficient quantities, they could serve as an alternative to many conventional plastics in use today. However, these microbial polymers are intracellularly stored, necessitating a more complex downstream extraction and purification process. Downstream processes often constitute the most financially burdensome stage in biomolecule production. One significant drawback of many existing extraction processes is their reliance on harsh organic solvents, such as chloroform, and high temperatures. This study presents and compares two novel downstream processes for the extraction and purification of poly(3-hydroxybutyrate) (PHB), a type of short-chain-length PHA, utilizing bio-based green solvents and natural deep eutectic solvents (NADES), respectively. The soil bacterium Pseudomonas putida, engineered to produce PHB from sugars, was adopted as a model for testing these extraction procedures. Initially, biomass was disrupted using a hypotonic buffer containing lysozyme to enhance the extraction efficiency in the downstream process. After extensive screening, the bio-based solvent ethyl acetate was selected for PHB extraction from P. putida biomass, yielding ∼ 95 wt% of the homo-polymer with a purity of ∼ 97 wt%, results comparable to those achieved with the traditional benchmark solvent, chloroform. Furthermore, a hydrophobic natural deep eutectic solvent (hydrophobic NADES) was synthesized, comprising L-menthol and acetic acid in a 1:3 M ratio, and employed as the extraction solvent in combination with methanol as the anti-solvent. The optimized extraction process resulted in a homo-polymer yield of ∼ 66 wt% with a high purity of ∼ 85 wt%. These results are promising considering the benefits associated with the use of NADES, they are less toxic and much easier to handle than ethyl acetate and have the potential to be recycled. Therefore, it represents a promising avenue for a more sustainable PHB extraction process, devoid of harmful organic solvents.

Food-protecting films based on soy protein isolate and natural deep eutectic solvents: Antimicrobial and antioxidant properties

Natural deep eutectic solvents (NADES) have just recently emerged as promising plasticizers in food coating applications owing to their excellent anti-frosting properties, low cost, and biosafety. Herein, we report for the first time the use of NADES as bioactive additives of soy protein isolate (SPI) to fabricate functional packaging materials. A neoteric eutectic solvent based on choline chloride/tannic acid (ChCl/TA) and the classical ChCl/citric acid mixture (ChCl/Cit) were explored to be integrated into the protein matrix at really high ratios (150 and 200 wt%). The resulting films were characterized by assessing morphological, physicochemical, and mechanical properties, as well as antioxidant and antimicrobial activities. The films exhibited a hydrophilic surface but limited water swelling (less than 10%), suggesting the formation of a crosslinked network between NADES and SPI. The ChCl/Cit films demonstrated potent antimicrobial activity in bacterial growth inhibition assay on chicken breast as well as in agar diffusion assays with inhibition zone diameters over 20 mm for gram+ and gram-bacteria, while ChCl/TA films showed the highest tensile strength (ranging from 744 to 2740 kPa), superior antioxidant activity (DPPH scavenging activity of ≈82%), and high light barrier properties, advantageous for storing light-sensitive food products. The incorporation of high concentrations of NADES in film production provides a novel and practical approach to improving the properties of protein materials for food packaging applications.

(Betaine: Citric Acid: H2O) a Natural Deep Eutectic Solvent (NaDES)-Mediated Efficient and Green Synthesis of 4-Benzylidene Isoxazol-5-one Derivatives

A biodegradable catalyst based on natural deep eutectic solvents (NaDESs) designed from Betaine and natural acids (Betaine: Citric Acid: H2O) with a molar ratio of (1:1.5:1) has been utilized in one-pot multi-component reaction for the synthesis of Isoxazol-5-ones derivatives in a mild, green and efficient manner. The reaction was carried out under different conditions that are, at 400C, ultrasonic and microwave. The developed method provided many advantages, including an excellent yield of up to 98% in a shorter reaction time, avoiding the use of toxic solvents and an easy handling process. Additionally, the use of NaDESs enabled the conservation of resources due to their simple preparation. The developed process adheres to the requirements of green chemistry by employing a bio-sourced and recyclable catalyst.

NaDES-based biorefinery of Spirulina (Arthrospira platensis): A new path for sustainable high value-added metabolites

To meet the criteria of modern extraction, it is essential to use solvents that simultaneously reach the standards of green chemistry and allow the extraction of a wide spectrum of bio-compounds. Natural Deep Eutectic Solvents (NaDES), as a green solution, meet this difficult task and represent a satisfactory alternative to organic solvents. Microalgae are recognized as a sustainable resource to produce polar and non-polar metabolites, such as carotenoids, free fatty acids (FFA) and phycobiliproteins. Among them, Spirulina (Arthrospira platensis) is one of the most studied, due to its strong potential for food, health and cosmetic. In this work, two biorefinery scenarios were investigated using polar and non-polar NaDES. The first one is a combination of a polar/non-polar sequential solid/liquid extraction together with a liquid–liquid extraction of the polar extract. The second scenario implements an innovative triphasic solid/liquid/liquid approach, based on the simultaneous use of polar and non-polar NaDES in the solid/liquid extraction step. Several NaDES were screened in this study to identify the best polar/non-polar NaDES pair. According to the results, the use of the triphasic approach allowed an increase of the productivity by a factor 4 for chlorophylls and FFA, and by a factor 2 for carotenoids. It was also interesting to note that the phycocyanin-enriched polar fraction achieves much higher levels of purity than the corresponding single-phase extraction for both applied biorefinery scenarios. These results pave the way for the first time for a microalgae biorefinery entirely based on the use of NaDES and industrially credible.

Effects of cryopreservation in the presence of Natural Deep Eutectic Solvents (NADESs) on sperm parameters

Natural Deep Eutectic Solvents (NADESs) are being considered as a potential alternative to traditional cryoprotective agents (CPAs) in sperm freezing. The study aimed to assess the effects of NADESs as a CPA on human sperm parameters. A total of 32 normozoospermic semen samples were collected from the Alzahra infertility treatment center (Iran) between July 2021 and September 2022. The samples were categorized into eight different groups: 1) a control (nonfrozen), and groups frozen with 2) SpermFreeze Solution, 3) ChX (Choline chloride and Xylitol), 4) ChS (Choline chloride and D-sorbitol), 5) ChG (Choline chloride and Glucose), 6) ChU (Choline chloride and Urea), 7) EtP (Ethylene glycol and l-proline), and 8) GlyP (Glycerol and l-proline). The study also analyzed the quality of sperm parameters, such as chromatin condensation and integrity, acrosome integrity, and survival, along with the expression of some genes that affect sperm fertility (TRPV1, TRPV4, SPACA3, and OGG1). The study found there were notable variations in sperm parameters (such as viability, chromatin condensation and integrity, and acrosome integrity) among frozen groups with some NADESs compared to the SpermFreeze Solution and control groups (P < 0.05). Analysis of gene expression demonstrated that the levels of TRPV1, TRPV4, SPACA3, and OGG1 genes were superior in the GlyP group compared to the other groups (P < 0.05). Additionally, the ChS and ChU groups exhibited preserved expression of these genes compared with the SpermFreeze Solution group. The use of NADESs led to the discovery of a more appropriate CPA that has low toxicity and is highly effective in maintaining the fertility potential of sperm.

NADES-assisted sample preparation as a greener alternative for mycotoxins determination in apple-based products

While impressive advancements have been reported in mycotoxin analysis over the last decade, very little has been done to realign the sample treatment to the green sample preparation principles, which are arising more and more relevance in the current analytical chemistry. In this regard, this work proposes the first NADES-assisted sample preparation for the extraction of mycotoxins in food samples.Two protocols using dispersive liquid–liquid microextraction (DLLME) and DLLME with solidification of floating organic drop (DLLME-SFO) assisted with a natural deep eutectic solvent (NADES) were developed and assessed as green sample preparation procedures to extract mycotoxins from apple-based products prior to HPLC-MS/MS analysis. The selected mycotoxins were alternariol, alternariol monomethyl ether, tentoxin and ochratoxin A, which are known to occur in these food matrices. The main variables affecting the extraction efficiency, such as volume of dispersive and extraction solvents, as well as the salting-out effect were evaluated and optimized using a central composite design. In addition, both methodologies were examined and compared in terms of greenness using the newly released metric tool AGREEprep. Due to the use of NADES, the DLLME-SFO method achieved a higher greenness score, and it was selected for further characterization. Matrix-matched calibration curves were used, showing a satisfactory linearity (R2 > 0.99). Limits of detection (LODs) and quantification (LOQs) were below 0.25 and 0.8 µg kg−1, respectively. Recoveries were above 72 % for all the mycotoxins studied in both apple juice and apple puree samples. The validated DLLME-SFO-HPLC-MS/MS method was applied to the analysis of commercial apple juice and puree samples. All the samples analysed were contaminated with at least one mycotoxin with a total concentration ranging from 0.4 to 10.5 µg kg−1.

Natural Deep Eutectic Solvents in the Synthesis of Inorganic Nanoparticles.

Natural deep eutectic solvents (NDESs), as a new type of green solvent, are used in many fields, including industry in extraction processes, medicine, pharmaceuticals, metallurgy, electrodeposition, separations, gas capture, biocatalysis and nanotechnology. Mainly due to their properties, such as simple preparation, environmental friendliness, biocompatibility and multifunctionality, they are being used in various fields of industry. This review aims to provide insight into the applications of natural deep eutectic solvents, specifically in nanotechnology processes. It focuses on the description of NDES and how their physicochemical properties are used to obtain functional nanomaterials, including metals, metal oxides and salts. It highlights how the use of NDESs to obtain a wide range of inorganic nanoparticles enables the elimination of disadvantages of traditional methods of obtaining them, including reducing energy consumption and functionalising nanoparticles in situ. In conclusion, recent advances and future directions in the development and applications of NDESs in nanotechnology are discussed with the aim of identifying unexplained scientific questions that can be investigated in the future.

Extraction of Bioactive Components from Chamaenerion angustifolium (L.) Scop. with Choline Chloride and Organic Acids Natural Deep Eutectic Solvents.

Chamaenerion angustifolium (L.) Scop. (fireweed) is a perennial herbaceous plant of the Onagraceae family widely used in folk and scientific medicine. It is a promising source of bioactive components. One of the modern trends in extraction is the use of natural deep eutectic solvents (NADESs) combined with ultrasound-assisted extraction (UAE). However, works devoted to the extraction of biologically active substances from C. angustifolium using NADESs are scarce. The aim of this work is a comprehensive study of UAE of bioactive components from C. angustifolium using NADESs based on choline chloride and malonic, malic, tartaric, and citric acids. The antioxidative properties, total phenols, and flavonoids content were estimated for NADES-based extracts. The reference solvents were water and 90% v/v ethanol. Volatile extracted components were identified using GC-MS. The kinetics of the UAE were studied at 45 °C for 20–180 min with water added to 30 wt% NADES. The power of the ultrasound was 120 W, and the frequency was 40 kHz. It was found that NADES choline chloride + citric acid is more effective for the extraction of bioactive components. For this, NADES UAE conditions were optimized following a Box–Behnken design of the experiment and a response surface methodology. The temperature ranged from 30 to 60 °C, the time of extraction ranged from 20 to 60, and the addition of water ranged from 30 to 70 wt%. We established the optimal extraction conditions: temperature 58 °C, time of extraction 35 min, and 70 wt% water. The obtained results expand the knowledge about the use of NADES for the extraction of biologically active compounds from cheap and available plant raw materials.

Utilization of waste mango peels for extraction of polyphenolic antioxidants by ultrasound-assisted natural deep eutectic solvent

Polyphenols extraction from natural sources has been of immense interest owing to growing demand for natural antioxidants in food, pharmaceutical, and cosmetic applications. Waste mango peels exhibit excellent prospects for target biomolecules. Conventional organic solvents possess intrinsic shortcomings. Thus, in this work, Natural Deep Eutectic Solvents (NADESs) are presented as non-toxic and eco-friendly alternatives for antioxidants recovery from mango peels. The use of NADES combined with ultrasound has been explored. At 20% water content, 50% duty cycle, 2 W/cm3 acoustic density, 30:1 (v/w) liquid: solid ratio, 0.3 mm particle size and 30 min, lactic acid-glucose (5:1), NADES provided highest TPC 69.85 mg GAE/g of MP, TFC 16.5 mg QE/g of MP and DPPH IC50 of 35.37 μg/mL. UA-NADES technique offered 1.4 times TPC, 1.7 times TFC, 1.9 times antioxidant activity also; 50% shorter time, and 25% reduced solvent consumption compared to batch method with 80% ethanol.

Antimicrobial and antiviral activity of selenium sulphide nanoparticles synthesised in extracts from spices in natural deep eutectic solvents (NDES)

Selenium sulphide is a well-known bioactive chemical, but its preparation in nanometric form stabilised in water has not been widely reported. In the article, extracts of cinnamon, curcumin, and pepper obtained using natural deep eutectic solvents (NDES) were used to obtain stable selenium sulphide nanoparticles. The analysis confirmed that selenium sulphide nanoparticles with an average crystallite size of 28–44 nm and a particle size of approximately 500 nm were successfully synthesised. The use of NDES stabilised the SeS2 nanoparticles and increased their bioactivity towards microorganisms. The obtained systems revealed high biocidal and antiviral activity against S. aureus, E. coli, P. aeruginosa, and C. albicans strains, Human influenza virus A/H1N1, and Betacoronavirus 1 (Human coronavirus HCoV-OC43). The SeS2 nanoparticles obtained in the NDES extract of curcuma strongly inhibited the growth of pathogenic fungi and bacteria with minimum biocidal concentration (MBC) values of 117.2, 117.2, 117.2, and 468.8 mg/dm3 against E. coli, P. aeruginosa, S. aureus, and C. albicans, respectively. The suspensions containing selenium sulphide nanoparticles stabilised by spice extracts were also highly active against influenza viruses and B-coronavirus, showing a reduction of over 99%.

Lignocellulosic biomass fractionation with the use of deep natural eutectic solvents

Brazil has a privileged position as a leader in the integral use of vegetable biomass because it has the largest biodiversity on the planet. Adding value to a refinery is associated with the treatment and disaggregation of the biomass components. There are processes applied to biomass fractionation to remove or break the layers of lignin and hemicellulose, which allows enzymes to access cellulose more easily. In view of this a great diversity of technological routes can be used, and alternative techniques that have been developed such as the use of the natural deep eutectic solvent (NADES). Thus, the objective of the present work was to perform the fractionation of the bark biomass from E. urograndis species into two fractions: cellulose rich fraction (CRF) and lignin rich fraction (LRF) using NADES. In this process three conditions were applied for biomass fractionation: conventional heating at 100ºC, microwave radiation with power of 600W and 1000 W, and room temperature at 25ºC. The percentages obtained through conventional heating were 72,25% of CRF, 27,75% of LRF; 72,54% of CRF with microwave radiation at a power of 1000W, 27,46% of LRF. The techniques used for characterization of CRF were: Fourier transformed infrared (FTIR) spectroscopy and X-ray diffractometry (XRD) for crystallinity analysis and scanning electron microscopy (SEM). For characterization of LRF the techniques were used: UV-vis and FTIR spectroscopy. The use of NADES a low cost, sustainable organic solvent combined with microwave radiation proved to be efficient for biomass fractionation.

Enhancing the Thermostability of Engineered Laccases in Aqueous Betaine-Based Natural Deep Eutectic Solvents.

In recent years, natural deep eutectic solvents (NADESs) have gained increasing attention as promising nontoxic solvents for biotechnological applications, due to their compatibility with enzymes and ability to enhance their activity. Betaine-based NADESs at a concentration of 25 wt % in a buffered aqueous solution were used as media to inhibit thermal inactivation of POXA1b laccase and its five variants when incubated at 70 and 90 °C. All the tested laccases showed higher residual activity when incubated in NADES solutions, with a further enhancement achieved also for the most thermostable variant. Furthermore, the residual activity of laccases in the presence of NADESs showed a clear advantage over the use of NADESs’ individual components. Molecular docking simulations were performed to understand the role of NADESs in the stabilization of laccases toward thermal inactivation, evaluating the interaction between each enzyme and NADESs’ individual components. A correlation within the binding energies between laccases and NADES components and the stabilization of the enzymes was demonstrated. These findings establish the possibility of preincubating enzymes in NADESs as a facile and cost-effective solution to inhibit thermal inactivation of enzymes when exposed to high temperatures. This computer-aided approach can assist the tailoring of NADES composition for every enzyme of interest.

Extraction of Phenolic Compound using Natural Deep Eutectic Solvent from Biomass Waste

Phenolic compounds are aromatic compounds known for their bioactive substances which can be found in plants. It has been widely used in various applications due to its antibiotics, anti-inflammatory, anti-allergic, and other benefits. There are various methods to extract the phenolic compounds from plants including ionic liquid, liquid-liquid extraction as well as supercritical extraction. However, all of these methods requires energy extensive, laborious processes, advanced technology, and generate toxic waste. Therefore, there is a growing need to find an alternative green extraction method to reduce the environmental impact while improving the efficiency of the extraction process. Thus, natural deep eutectic solvents (NADES), a combination of two or more components that comes from primary metabolites like organic acids, choline chloride, or sugar, are able to form liquids upon mixing with lower melting point of individual constituents due to hydrogen bond interactions were proposed as alternatives to conventional extraction methods. Therefore, this research determined the suitable combination of NADES solvents (hydrogen bond acceptor/donor ratio) for extraction of phenolic compounds from biomass waste which included young and mature coconut shells and coconut husk, banana peel, empty fruit bunch, and palm oil fruit husk. The extracted compound was analysed using fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) to identify the functional groups and type of phenolic compounds present. The best biomass waste was coconut shell and the best NADES combination was choline chloride and ascorbic acid at 1:2 molar ratio. The FTIR analysis of coconut shell extracted by NADES showed peaks at 3404 cm−1 and 3523 cm−1 indicating OH stretching followed by 2915 cm−1, 1388 cm−1 to 1473 cm−1, and 1674 cm−1 showing C-H stretching, sp3 C-H band and C=C stretch respectively. As for GC-MS analysis, 26 compounds were detected and four phenolic compounds were identified at peaks 2, 13, 22, and 25. The research was successful in determining the best biomass waste and NADES combination for highest total phenol. The use of NADES was able to extract more phenolic compound from coconut shell than water due to the hydrogen bond between the choline chloride and ascorbic acid.

Biomass Valorization Using Natural Deep Eutectic Solvents: What's New in France?

With the growing interest in more environmentally friendly solvents and processes, the introduction of Natural Deep Eutectic Solvents (NaDES) as low cost, non-toxic and biodegradable solvents represent a new opportunity for green and sustainable chemistry. Thanks to their remarkable advantages, NaDES are now arousing growing interest in many fields of research such as food, health, cosmetics and biofuels. Around the world, NaDES are seen as a promising alternative to commonly used petrochemical solvents. The objective of this review is to draw up a panorama of the existing skills on NaDES in French laboratories and industries for the valuation of natural products. This review therefore focuses on current applications, skills and perspectives, in order to analyze the place of French research in the use of NaDES for the valorization of biomass since 2015.

Utilization of pomegranate peel waste: Natural deep eutectic solvents as a green strategy to recover valuable phenolic compounds

Pomegranate peel is an agro-industrial waste rich in phenolic compounds that can be employed like natural antioxidants in the food and pharmaceutical industry. In this study, five choline chloride-based natural deep eutectic solvents (NADES), which contained glucose, sucrose, glycerol, lactic acid, and citric acid as a hydrogen bond donor, were physicochemically characterized and tested for recovery of phenolics from pomegranate peel. The efficiency of the NADES in extracting phenolics from pomegranate peel has also been compared with that of conventional ethanolic extraction. The choline chloride and lactic acid (CC-LAC) NADES proved to be the most appropriate for the extraction of phenolics from pomegranate peel (4.14 mg EAG mL−1) if compared to the other tested NADES (range 0.81–3.84 mg EAG mL−1) and also if compared with the ethanolic solution (3.55 mg EAG mL−1). The optimization of the extraction conditions of phenolics from pomegranate waste peels using CC-LAC was carried out by multivariate strategies such as factorial design and response surface methodology. The optimal extraction conditions were 20 g of CC-LAC per g of pomegranate peel, 35% of lactic acid in relation to choline chloride, and 25 min of extraction at 45 °C. Under optimal extraction conditions, the phenolic recovery increased by 54.6%, when compared to CC-LAC non-optimized, and by 84.2%, when compared to ethanolic extraction. Our results, therefore, demonstrated that the use of NADES is a simple, cost-effective, more sustainable, and greener alternative for the extraction of the phenolics from pomegranate peel, over conventional extraction methods.

Biocompatible natural deep eutectic solvent-based extraction and cellulolytic enzyme-mediated transformation of Pueraria mirifica isoflavones: a sustainable approach for increasing health-bioactive constituents

The presence of specific gut microflora limits the biotransformation of Pueraria mirifica isoflavone (PMI) glycosides into absorbable aglycones, thus limiting their health benefits. Cellulolytic enzyme-assisted extraction (CAE) potentially solves this issue; however, solvent extraction requires recovery of the hydrophobic products. Here, we established the simultaneous transformation and extraction of PMIs using cellulolytic enzymes and natural deep eutectic solvents (NADESs). The NADES compositions were optimized to allow the use of NADESs as CAE media, and the extraction parameters were optimized using response surface methodology (RSM). The optimal conditions were 14.7% (v/v) choline chloride:propylene glycol (1:2 mol ratio, ChCl:PG) at 56.1 °C for the cellulolytic enzyme (262 mU/mL) reaction in which daidzin and genistin were extracted and wholly transformed to their aglycones daidzein and genistein. The extraction of PMIs using ChCl:PG is more efficient than that using conventional solvents; additionally, biocompatible ChCl:PG enhances cellulolytic enzyme activity, catalyzing the transformation of PMIs into compounds with higher estrogenicity and absorbability.

Choline Chloride/Glycerol Promoted Synthesis of 3,3-Disubstituted Indol- 2-ones

Objective:: 3,3-Disubstituted indol-2-one derivatives have wider applications in pharmaceuticals and they are key intermediates for the synthesis of many kinds of drug candidates. The development of an efficient and practical method to prepare this class of compound is highly desirable from both environmental and economical points of views. Methods:: In order to establish an effective synthetic method for preparing 3,3-disubstituted indol- 2-one derivatives, the bis-condensation reaction of isatin and 1H-indene-1,3(2H)-dione was selected as a model reaction. A variety of natural deep eutectic solvents (NADESs) were prepared and used for this reaction. The generality and limitation of the established method were also investigated. Results:: It was found that model reaction can be carried out in natural deep eutectic solvent (NADES) based on choline chloride (ChCl) at 80°C under microwave irradiation. This protocol with a broad substrate applicability afforded various 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene- 1,3(2H)-dione) derivatives in high yields. Conclusion:: A simple and efficient procedure has been developed for synthesis of 2,2'-(2-oxoindoline- 3,3-diyl)bis(1H-indene-1,3(2H)-dione), spiro[indoline-3,7'-pyrano[5,6-c:5,6-c']dichromene]- 2,6',8'-trione, and spiro[indoline-3,9'-xanthene]trione via bis-condensation between isatin with 1,3- indandione, 4-hydroxycoumarin or 1,3-cyclohexanedione in natural deep eutectic solvent (NADES) based on choline chloride (ChCl) and glycerol (Gl) under microwave irradiation. The salient features of this protocol are avoidance of any additive/catalyst and toxic organic solvent, clean reaction profiles, non-chromatographic purification procedure, and high to excellent yield. Furthermore, the use of NADES as green reaction medium reduces burden on environment and makes the present method environmentally sustainable.

A Sustainable Approach for Extracting Non-Extractable Phenolic Compounds from Mangosteen Peel Using Ultrasound-Assisted Extraction and Natural Deep Eutectic Solvents

Mangosteen (Garcinia mangostana L.) peel is a potential source of phenolic compounds with beneficial properties. Natural deep eutectic solvents (NaDES) have been considered an environmentally friendly and cheap alternative to conventional organic solvents. In this work, a green extraction methodology was developed using ultrasound-assisted extraction (UAE) and NaDES for the extraction of antioxidant non-extractable polyphenols (NEPs) from mangosteen peel. To select the best NaDES to extract NEPs from mangosteen peel, seven NaDES were studied. Antioxidant capacity and total phenolic and proanthocyanidin contents were determined for the extracts. The molecular weights for the NEPs present in those extracts were evaluated by size exclusion chromatography. Experimental results showed that choline chloride–lactic acid (1:2) was the NaDES allowing the highest antioxidant proanthocyanidin content in the extracts. A Box–Behnken experimental design was employed to optimize the main parameters in UAE with NaDES: water percentage, ultrasound amplitude, and extraction time. The optimal extraction conditions were 18.8% (v/v) water, 60% ultrasound amplitude, and 15 min as the extraction time. In addition, the cytotoxicity of the NEP extracts obtained under optimal extraction conditions was evaluated. Results indicated for the first time that the use of NaDES in combination with UAE could be a sustainable alternative for the extraction of antioxidant NEPs from mangosteen peel for important applications in the food, pharmaceutical, agrochemical, and cosmetic fields, as the extracts presented low cytotoxicity.

Immobilized MAS1 Lipase-catalyzed Synthesis of n-3 PUFA-rich Triacylglycerols in Deep Eutectic Solvents.

n-3 polyunsaturated fatty acids (PUFA)-rich triacylglycerols (TAG) with many beneficial effects are still difficult to be synthesized efficiently and rapidly by current synthetic techniques. This study reports the fatty acid specificity of immobilized MAS1 lipase and its efficient synthesis of n-3 PUFA-rich TAG by esterification of glycerol with n-3 PUFA in natural deep eutectic solvents (NADES) systems. Immobilized MAS1 lipase showed the highest preference for capric acid [C10:0, the highest specificity constant (1/α)=1] whereas it discriminated strongly against docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) due to their lowest specificity constants (1/α=0.19 and 0.2). Moreover, the highest n-3 PUFA-rich TAG content (55.8%) with similar n-3 PUFA composition to the substrate was obtained in choline chloride/glycerol (CG) system. There was a 1.38-fold increase of TAG content in CG system compared with that in the solvent-free system. Interestingly, immobilized MAS1 lipase exhibited no regiospecificity in the solvent-free and various NADES systems. Besides, the potential reaction mechanism of immobilized MAS1 lipase-catalyzed esterification of glycerol with n-3 PUFA in NADES systems was described. It was found that the use of NADES as solvents could greatly enhance TAG content, and make it easy to separate the product. These results indicated that immobilized MAS1 lipase is a promising biocatalyst for the efficient synthesis of n-3 PUFA-rich TAG by esterification of glycerol with n-3 PUFA in NADES systems.