The perspectives of natural deep eutectic solvents in agri-food sector

In the paper

“They are dependent on the chemical nature of its components and on their intermolecular interactions (Liu et al. 2018).”

What the sources say

• Supported

  The ‘Physicochemical Interactions of NADES Components’ section (page not available in our copy) identifies chemical functional groups in the constituents and says their intermolecular hydrogen-bonding network modifies the physicochemical environment. The ‘Conductivity and Viscosity’ section also links a solvent property, viscosity, to intermolecular forces. (LLM, conf=0.90)

  cites Liu et al. 2018 source

In the paper

“Furthermore, NADES were also suggested as solvents for protein (e.g.lysozyme, amylase, photosynthetic enzymes) and DNA stabilization (Choi et al. 2011;Dai et al. 2014;Milano et al. 2017;Xin et al. 2017).”

What the sources say

• Partly supported

  In the paper’s discussion of drought and germination (page unavailable), the authors suggest that proteins could be conserved in NADES and enzymes could remain stable. The solubility discussion reports that salmon DNA dissolves in a tested NADES, but does not suggest that NADES stabilizes DNA. Thus, Choi et al. support the protein-stabilization part, not the DNA-stabilization part. (LLM, conf=0.86)

  cites Choi et al. 2011 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Dai et al. 2014 source
• ?Not checked — no full text of the sourcecites Milano et al. 2017 source

In the paper

“The physicochemical properties of the NADES (viscosity, conductivity, density and polarity) affect their end-use (Choi et al. 2011;Dai et al. 2013b).”

What the sources say

• Partly supported

  In the paper’s main text (page not provided), Choi et al. describe NADES as viscous liquids and show that different NADES dissolve compounds to different degrees. They also propose uses as extraction and reaction solvents. Our copy does not establish that conductivity, density, or polarity affect end-use, so the full list of properties is not supported. (LLM, conf=0.84)

  cites Choi et al. 2011 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Dai et al. 2013b

In the paper

“The authors also observed that the oral administration of rutin with NADES improved bioavailability of this polyphenol compared to the water suspension.”

What the sources say

• Supported

  The Conclusions state that oral rutin in proline/glutamic acid NADES improved bioavailability compared with a water suspension. The Results (§2.3) report approximately twice the relative bioavailability for NADES in mice. (LLM, conf=0.95)

  cites Faggian et al. (2016) source

In the paper

“In this study it was shown that the total vapor pressure was dominated by the constituent with the highest vapor pressure.”

What the sources say

• Supported

  The results passage under “Suitability of HS-GC-MS Method for” explicitly states that the total vapor pressure of the six hydrophobic deep eutectic solvents was dominated by the constituent with the highest vapor pressure. The citing sentence accurately paraphrases that finding. (LLM, conf=0.95)

  cites Dietz et al. (2019) source

In the paper

“Additionally, formulation of resveratrol with NADES increased its matrix metalloproteinase-9 (MMP-9) inhibition activity (Shamseddin et al. 2017), while dissolution of salsalate in NADES allowed in vitro evaluation of its bioactivity (Rozema et al. 2015).”

What the sources say

• Supported

  The Conclusions state that dissolving salsalate in the NADES PCH increased its solubility in cell-culture medium, allowing treatment of cells at concentrations sufficient for full dose-response curves. This directly supports the claim that the formulation enabled in vitro evaluation of salsalate’s bioactivity. (LLM, conf=0.93)

  cites Rozema et al. 2015 source

In the paper

“Dietz et al. (2019) confirmed that the total vapor pressures of six hydrophobic NADES and the partial pressures of their constituents were very low in comparison to vapor pressures of commonly used volatile organic solvents using new and validated HS-GC-MS method.”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Dietz et al. (2019) source

In the paper

“In line with that, the total vapor pressure of investigated NADES were strongly depended on the vapor pressures of the constituents used for their synthesis following the order menthol > thymol > decanoicacid > lidocaine.”

What the sources say

• Supported

  In “Total Vapor Pressures of Hydrophobic DESs and Partial Pressure of the DES Constituents,” the paper says total vapor pressure is dominated by the constituent with the highest vapor pressure and gives the exact order stated in the claim. The paper calls the investigated mixtures hydrophobic DESs. (LLM, conf=0.94)

  cites Dietz et al. (2019) source

In the paper

“Applying the in vivo model with rats, Faggian et al. (2016) managed to achieve a 100% improvement in the absorption of rutin with NADES (proline:glutamic acid (2:1)) in comparison with the water suspension.”

What the sources say

• Partly supported

  Results §2.3 reports approximately 100% greater extent of rutin absorption with proline/glutamic acid (2:1) NADES than with a water suspension. But Results §2.3 and Experimental §4.4 identify the animals as mice, not rats. (LLM, conf=0.94)

  cites Faggian et al. (2016) sourceExperimental — accuracy not yet measured

In the paper

“According to obtained results of biochemical analysis of animal's blood, investigated NADESs exhibited hepatotoxic effect.”

What the sources say

• Supported

  The Results and Discussion, In vivo analysis section (page not provided), says blood biochemical changes in NADES-treated mice were indicative of hepatocellular injury. The Methods, In vivo assessment section describes the acute toxicity study in mice. (LLM, conf=0.93)

  cites Mbous et al. 2017 source

In the paper

“Hydrophobic NADES consisting of decanoic acid and various quaternary ammonium salts were shown to be efficient for the recovery of volatile fatty acids from diluted aqueous solutions (van Osch et al., 2015), although a few years later van Osch et al.”

What the sources say

• Partly supported

  The paper’s extraction discussion reports that decanoic-acid/quaternary-ammonium-salt DESs extracted volatile fatty acids from diluted aqueous solutions more efficiently than trioctylamine. The Introduction and Conclusions call them hydrophobic DESs, not natural deep eutectic solvents (NADES), so the “NADES” designation is not supported by our copy. The supplied passages have section labels but no page numbers. (LLM, conf=0.86)

  cites van Osch et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Plasma levels of berberine following the administration of three NADES were significantly higher than the plasma level observed with the water suspension.”

What the sources say

• Partly supported

  The Results (§2.3) report significantly higher berberine plasma levels for all three NADES than for water suspension at 30 minutes. The claim omits that time qualifier: the paper reports additional significant differences at 10, 60, and 180 minutes only for NADES B and C, not all three. (LLM, conf=0.83)

  cites Sut et al. 2017 sourceExperimental — accuracy not yet measured

In the paper

“Similar findings were reported for anthocyanins from purple and orange petals of Catharanthus roseus in lactic acid-glucose (LGH) (Dai et al. 2016).”

What the sources say

• Partly supported

  Section 3.1.1 reports extracting anthocyanins from purple and orange Catharanthus roseus petals with LGH. But the stability test used a cyanidin reference-standard solution, not anthocyanins extracted from either petal color (Sections 2.4 and 3.3; page numbers unavailable). The reported stability enhancement therefore does not establish the same result for both petal extracts. (LLM, conf=0.88)

  cites Dai et al. 2016 sourceExperimental — accuracy not yet measured

In the paper

“so these results are in line with the reported relationship between higher viscosity and higher cell lethality (Hayyan et al. 2016).”

What the sources say

• Supported

  In Results and discussion, the paper states that its more viscous NADES mixtures had the lowest average IC50 values across the examined cells and explicitly says that high viscosity is often associated with increased lethality. This supports the cited relationship as an association, not a claim that viscosity alone causes cell death. (LLM, conf=0.94)

  cites Hayyan et al. 2016 source

In the paper

“The authors concluded that the increase in bioavailability is mainly related to the solubilization properties of the applied eutectic mixtures.”

What the sources say

• Supported

  The Discussion states that the similar pharmacokinetic profiles of the tested eutectic mixtures suggest the observed increase in berberine bioavailability is mainly related to their solubilization properties. This matches the citing sentence’s attribution to the authors’ conclusion. (LLM, conf=0.95)

  cites Sut et al. 2017 source

In the paper

“In addition, LD 50 values were determined (LD 50 =1.84and 1.24 g mL -1 , for ChCl:fructose and ChCl:glucose, respectively).”

What the sources say

• Partly supported

  The Results and Discussion, under “In vivo analysis” (page unavailable), says the paper recorded LD50 values for the solvents in mice and points to Table 5. The passages available from our copy do not give the claimed values of 1.84 and 1.24 g mL−1, so those numbers cannot be verified. (LLM, conf=0.80)

  cites Mbous et al. 2017 sourceExperimental — accuracy not yet measured

In the paper

“The authors conclude that the NADES can be administered orally at moderate doses without major health hazards.”

What the sources say

• Supported

  The Conclusions state that the compounds used to prepare the study’s NADES can be administered orally at moderate doses without major health hazards. The same section discusses oral administration of the proline/glutamic acid NADES in mice, supporting the claim about this formulation. (LLM, conf=0.91)

  cites Faggian et al. (2016) source

In the paper

“Following the same approach (in vivo model with rats), the same research group (Sut et al. 2017) managed to improve bioavailability of berberin by dissolving it in three NADES (proline:malic acid:lactic acid:water (1:0.2:0.3:0.5),proline:malic acid (1:2) and proline:urea (2:1)).”

What the sources say

• Partly supported

  The Discussion reports increased berberine bioavailability after administration in three NADES, but the Introduction and Methods identify the animals as mice, not rats. The Discussion also gives the proline:malic acid formulation as 2:1, rather than the citing sentence’s 1:2. No page numbers are provided in our copy. (LLM, conf=0.93)

  cites Sut et al. 2017 sourceExperimental — accuracy not yet measured

In the paper

“Apart from food/feed, pharmaceutical and nutraceutical applications, NADES extracts from agro-industrial sources can be considered for the production of green agrochemicals (fertilizers and diverse pesticides) to address the global challenges for sustainable food production (Mouden et al. 2017).”

What the sources say

• Partly supported

  The Introduction and Concluding remarks (page unavailable) propose NADES as green solvents for plant-derived insecticidal crop-protection agents, supporting the pesticide-related part of the claim. Our copy does not support the added specifics that the extracts come from agro-industrial sources or could be used to produce fertilizers and diverse pesticides. (LLM, conf=0.88)

  cites Mouden et al. 2017 sourceExperimental — accuracy not yet measured

In the paper

“Relying on the findings of Faggian et al. (2016) and Sut et al. (2017), the ability of NADES to improve bioavailability opens interesting possibilities for their use as vehicles of bioactive compounds for pharmaceutical and nutraceutical applications.”

What the sources say

• Supported

  The Conclusions report improved bioavailability of rutin administered with a proline/glutamic acid NADES in mice and describe NADES as potential solubilizing and formulating agents for polyphenols. The Introduction identifies their possible use as vehicles for rutin administration, while the paper also discusses pharmaceutical and nutraceutical applications. The citing sentence presents these as possibilities, not established applications. (LLM, conf=0.92)

  cites Faggian et al. (2016) source
• Supported

  The Discussion reports increased berberine bioavailability in mice given NADES formulations compared with an aqueous suspension. The Introduction describes potential pharmaceutical and nutraceutical uses, supporting the citing sentence’s proposed applications rather than claiming they have been established. (LLM, conf=0.91)

  cites Sut et al. (2017) source

In the paper

“The majority of investigated compounds were classified as readily biodegradable compounds (Hou et al. 2013;Huang et al. 2017;Radošević et al. 2015;Wen et al. 2015;Zhao et al. 2015).”

What the sources say

• Supported

  The Results and Discussion (Biodegradability) state that all tested cholinium amino-acid ionic liquids exceeded 60% biodegradation after 28 days in both tests and therefore could be called ‘readily biodegradable.’ This supports the claim that a majority of the compounds investigated in this study received that classification; it does not establish the results of the other studies cited in the same sentence. (LLM, conf=0.94)

  cites Hou et al. 2013 source
• ?Not checked — no full text of the sourcecites Huang et al. 2017 source
• ?Not checked — no full text of the sourcecites Radošević et al. 2015 source

In the paper

“It was proven that proline:glutamic acid (2:1) (Faggian et al. 2016), proline:malic acid:lactic acid:water (1:0.2:0.3:0.5),proline:malic acid (1:2) and proline:urea (2:1) NADES (Sut et al. 2017) can be administered orally at moderate doses without major health hazards on rats.”

What the sources say

• Partly supported

  Faggian et al. is cited for proline:glutamic acid (2:1), not the other formulations. The Conclusions state that its components can be administered orally at moderate doses without major health hazards, and the Experimental Section (§4.4) reports oral administration of the NADES to mice. The paper does not establish safety in rats or report a direct health-hazard assessment. (LLM, conf=0.88)

  cites Faggian et al. 2016 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion identifies the three NADES attributed to Sut et al., and Methods §4.4 reports their oral administration with berberine to mice. The paper does not establish that they can be given to rats without major health hazards: it measured berberine blood levels, not health outcomes. The Discussion also lists the proline–malic acid ratio as 2:1, rather than the claimed 1:2. The proline–glutamic acid mixture is attributed to a different citation in the citing sentence. (LLM, conf=0.88)

  cites Sut et al. 2017 sourceExperimental — accuracy not yet measured

In the paper

“The stabilizing ability of NADES is explained by the existence of intermolecular interactions, mainly hydrogen bonding between solutes and NADES that stabilize solutes molecules and lead to reduction in solutes movement and consequently protect solutes from oxidative degradation(Dai et al. 2016; de los Ángeles Fernández et al. 2018a).”

What the sources say

• Partly supported

  Section 3.3 (page unavailable) proposes that hydrogen bonding between cyanidin and LGH reduces solute movement and contact with oxygen, thereby reducing oxidative degradation. The paper calls this a hypothesis and discusses a specific cyanidin–NADES system; the claim presents it as an established explanation for NADES and solutes generally. (LLM, conf=0.87)

  cites Dai et al. 2016 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites de los Ángeles Fernández et al. 2018a

In the paper

“It was demonstrated that NADES biodegradation is associated with their chemical nature (Hou et al. 2013;Huang et al. 2017;Radošević et al. 2015;Wen et al. 2015;Zhao et al. 2015).”

What the sources say

• Partly supported

  The Results and Discussion (Biodegradability; page not provided) report that biodegradability varies with the structures of amino acid anions. That supports the chemical-nature relationship, but the compounds studied are cholinium amino acid ionic liquids, not NADES; the paper does not establish the claim for NADES. (LLM, conf=0.88)

  cites Hou et al. 2013 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Huang et al. 2017 source
• ?Not checked — no full text of the sourcecites Radošević et al. 2015 source

In the paper

“Furthermore, choline chloride based NADES were effective in the extraction and solubilization of ochratoxin A, giving a recovery of up to 89% for spiked samples of durum wheat, bread crumbs and biscuits.”

What the sources say

• Supported

  The Results and Discussion report that choline chloride–based eutectic mixtures extracted and solubilized ochratoxin A with up to 89% recovery from spiked wheat. The same section reports testing spiked durum wheat, bread crumbs, and biscuits; their mean recoveries ranged from 70% to 88%. Thus 89% is the reported maximum, not a recovery reported for each product. (LLM, conf=0.88)

  cites Piemontese et al. (2017) source

In the paper

“In comparison to the heating method, the authors gave the advantage to the grinding method as it resulted in NADES of high purity.”

What the sources say

• ?Not checked — no full text of the sourcecites Florindo et al. (2014) source

In the paper

“Referring to all mentioned above, NADES have a great potential for food applications.”

In the paper

“The preparation of NADES by heating and stirring is the most common method in the literature (Florindo et al. 2014).”

What the sources say

• ?Not checked — no full text of the sourcecites Florindo et al. 2014 source

In the paper

“Even when the same preparation method is applied, the difference in reported physicochemical properties of particular NADES can be observed (Lapeña et al. 2019).”

What the sources say

• ?Not checked — no full text of the sourcecites Lapeña et al. 2019 source

In the paper

“there has been a growing interest in natural additives and different phytochemicals serving not only as nutrients, but also as functional food ingredients, including antioxidants, antimicrobials, food aromas and colorants (Kallel et al. 2014).”

What the sources say

• ?Not checked — no full text of the sourcecites Kallel et al. 2014 source

In the paper

“However, Florindo et al. (2014) found that method inappropriate as applied for the preparation of five cholinum chloride:carboxylic acids NADES due to the generation of impurities ranging from 5% to 30%.”

What the sources say

• ?Not checked — no full text of the sourcecites Florindo et al. (2014) source

In the paper

“Majority of NADES combinations are regarded as highly biodegradable and of low toxicity (Paiva et al. 2014;Radošević et al. 2016a;Wen et al. 2015).”

What the sources say

• ?Not checked — no full text of the sourcecites Paiva et al. 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Radošević et al. 2016a
• ?Not checked — no full text of the sourcecites Wen et al. 2015 source

In the paper

“In a number of experiments extraction yields by NADES were higher than that with conventional organic solvents (Dai et al., 2013a;de los Ángeles Fernández et al. 2018a;Jeong et al. 2017;Liu et al. 2017b).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Dai et al., 2013a
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites de los Ángeles Fernández et al. 2018a
• ?Not checked — no full text of the sourcecites Jeong et al. 2017 source

In the paper

“As far as the strength of hydrogen bonds is concerned, it fully correlates with the temperature of phase transition, viscosity, stability and dissolving properties of a given eutectic solvent (Jablonskýa et al. 2018).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Jablonskýa et al. 2018

In the paper

“Simple and ease preparation of NADES with high purity and without waste generation (Pena-Pereira et al. 2015), meets the 12 principles of green chemistry (Anastas and Eghbali 2010).”

What the sources say

• ?Not checked — no full text of the sourcecites Pena-Pereira et al. 2015 source
• ?Not checked — no full text of the sourcecites Anastas and Eghbali 2010 source

In the paper

“Relying on the results of FT-IR and 1H NMR experiments, Dai et al. (2015) demonstrated that dilution with water caused the interactions HBD-HBA weaken gradually and even disappeared completely at around 50% (v/v) water addition.”

What the sources say

• ?Not checked — no full text of the sourcecites Dai et al. (2015) source

In the paper

“As there is insufficient basic knowledge concerning NADES, trial and error presents a strategy for discovering particular molar ratios of HBA and HBD capable of forming eutectic liquids.”

In the paper

“Apart from their extraction ability, increased stability of natural compounds during extraction and storage (such as phenolic compounds, β-carotene and α-tocopherol) is another advantage of using NADES over traditional solvents (Dai, Verpoorte, and Choi 2014;de los Ángeles Fernández et al. 2018a;Milano et al. 2017;Xin et al. 2017;Zahrina et al. 2018).”

What the sources say

• ?Not checked — no full text of the sourcecites Dai, Verpoorte, and Choi 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites de los Ángeles Fernández et al. 2018a
• ?Not checked — no full text of the sourcecites Milano et al. 2017 source

In the paper

“Referring to the authors, the increased anti-proliferative effect of the ChCl:malic acid extract compared to the other extracts could be partly explained by the effect of the NADES composition itself, since some organic acids, including malic acid, reveal many beneficial pharmacological effects, such as anti-inflammatory activity and antioxidant capacity.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Radošević et al. (2016a)

In the paper

“Available strategies to reduce NADES viscosity are heating and simple dilution of NADES with water (Aroso et al., 2017;Cardellini et al. 2014;Craveiro et al. 2016;Dai et al. 2013b;2015;Xin et al. 2017).”

What the sources say

• ?Not checked — no full text of the sourcecites Aroso et al., 2017 source
• ?Not checked — no full text of the sourcecites Cardellini et al. 2014 source
• ?Not checked — no full text of the sourcecites Craveiro et al. 2016 source

In the paper

“The high viscosity and reduced mobility of NADES at room temperature is associated with the extensive and complex hydrogen bonding between the HBD and HBA ( Yan et al. 2017; Altamash et al. 2018).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Yan et al. 2017
• ?Not checked — no full text of the sourcecites Altamash et al. 2018 source

In the paper

“In comparison to hydrophilic NADES, hydrophobic NADES were shown to possess lower viscosity as a result of eliminating the Coulombic charge interactions (Ribeiro et al. 2015).”

What the sources say

• ?Not checked — no full text of the sourcecites Ribeiro et al. 2015 source

In the paper

“On the other hand, Dai et al. (2014) indicated that higher viscosity of NADES contributed to the higher stability of some natural compounds (e.g.phenolic compounds) due to the hydrogen bonding interactions between solutes and NADES molecules.”

What the sources say

• ?Not checked — no full text of the sourcecites Dai et al. (2014) source

In the paper

“With increasing temperature the viscosity of NADES decreases with increase in the shear rate due to higher intermolecular forces at higher temperatures and the structural breakdown caused by the thermal expansion and shearing effect (Yan et al. 2017).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Yan et al. 2017

In the paper

“The water activity of NADESs decreased in the following sequence: MA:BA > CA:BA >MA:Fru ≅ MA:Glu > U:Fru ≅ U:Glu > CA:CC ≅ CA:Fru > MA:CC >CA:Glu > Glu:CC ≅ Fru:CC in the range between 0.653 and 0.177.”

What the sources say

• ?Not checked — no full text of the sourcecites Gómez et al. (2019) source

In the paper

“The authors demonstrated that pretreatment at 10% (w/v) solids loading followed by enzymatic hydrolysis at 25% (w/v) solids loading is the most effective integrated biorefinery process using NADES pretreated rice straw.”

What the sources say

• ?Not checked — no full text of the sourcecites Kumar et al. (2018) source

In the paper

“Using choline chloride/glycerol treated rice straw, the authors managed to obtain 226.7 g L -1 of reducing sugars with a saccharification efficiency of 87.1% at 20% solids loading and 12 FPU Cellic Ctec2.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kumar et al. (2016)

In the paper

“In their case, all samples reached a water activity higher than 0.900 when 60% of water was incorporated.”

What the sources say

• ?Not checked — no full text of the sourcecites Gómez et al. (2019) source

In the paper

“All tested NADES had higher extraction capacity for vanillin than ethanol, commonly used for the extraction of flavoring compounds.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites González et al. (2017)

In the paper

“Using NADES as solvents, phenolic compounds were successfully extracted from fruits, medicinal plants and food by-products (Ramón et al. 2017).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ramón et al. 2017

In the paper

“High thermal stability of NADES potentially makes them suitable for various food applications which include thermal processing.”

In the paper

“The same authors demonstrated that the incorporation of water to NADES causes a gradual increase in the water activity.”

What the sources say

• ?Not checked — no full text of the sourcecites Gómez et al. (2019) source

In the paper

“In vitro assay using MCF-7 and HeLa tumor cells were applied for the first time by Radošević et al. (2016a) to demonstrate that NADES enhanced the biological activities of extracts from grape skin, which contained phenolic compounds.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Radošević et al. (2016a)

In the paper

“The following NADES satisfied these criteria: thymol and coumarin (2:1), thymol and menthol (1:1), thymol and coumarin (1:1), thymol and menthol (1:2) and 1-tetradecanol and menthol (1:2) (Van Osch et al. 2019).”

What the sources say

• ?Not checked — no full text of the sourcecites Van Osch et al. 2019 source

In the paper

“Gómez et al. (2019) measured a w value of a range of NADES prepared with citric acid (CA), malic acid (MA), glucose (Glu), fructose (Fru), urea (U), β-alanine (BA) and choline chloride (CC).”

What the sources say

• ?Not checked — no full text of the sourcecites Gómez et al. (2019) source

In the paper

“Similar observations were reported by Rajan, Prabhavathy, and Ramesh (2015), who found higher antioxidant and antimicrobial activity of NADES extracts of ginger than those obtained with conventional solvents.”

What the sources say

• ?Not checked — no full text of the sourcecites Rajan, Prabhavathy, and Ramesh (2015) source

In the paper

“It was found that all prepared NADES exhibited the liquid-state behavior at all temperatures over the applied frequency from 0.1-100 rad s -1 (G''>G').”

What the sources say

• ?Not checked — no full text of the sourcecites Altamash et al. (2017 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [2018]

In the paper

“Additionally, formulation of resveratrol with NADES increased its matrix metalloproteinase-9 (MMP-9) inhibition activity (Shamseddin et al. 2017), while dissolution of salsalate in NADES allowed in vitro evaluation of its bioactivity (Rozema et al. 2015).”

What the sources say

• ?Not checked — no full text of the sourcecites Shamseddin et al. 2017 source

In the paper

“Performed in vitro studies on cell cultures demonstrated the variation in cell sensitivity that could be associated with the application of different experimental conditions as well as by the sensitivity of used cell types.”

In the paper

“The important factors for the toxicity estimation include: chemical kinetics (absorption, biotransformation, distribution and excretion) of investigated compounds that have direct influence on the concentration to which cells are exposed in vivo (Eisenbrand et al. 2002).”

What the sources say

• ?Not checked — no full text of the sourcecites Eisenbrand et al. 2002 source

In the paper

“In addition, it was demonstrated that UAE was characterized by longer extraction time in comparison to MAE.”

In the paper

“Their results suggest that a combination of factors, such as the hydrophobicity/hydrophilicity of the HBD, the nature of the ABS components, as well as the tie-line length, allows the preparation of systems in which the HBA:HBD stoichiometry used in NADES preparation is maintained in the phases in equilibrium, thus behaving as de facto ternary systems.”

What the sources say

• ?Not checked — no full text of the sourcecites Farias et al. (2017) source

In the paper

“Later, Wang et al. (2017a) introduced the concept of mechanochemical extraction, which is characterized by a disruption of biomolecular lipid layers and cell walls in a multidirectional, simultaneous mechanical in-liquid smashing, which results in the release of bioactive compounds such as alkaloids, flavonoids, and catechins (Wang et al., 2017a).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wang et al. (2017a)

In the paper

“Hayyan et al. (2013) confirmed the higher toxicity of tested NADES on brine shrimp than that of their individual components, while Radošević et al. (2015) found similar observation in the case of ChCl:oxalic acid NADES on two cell lines.”

What the sources say

• ?Not checked — no full text of the sourcecites Hayyan et al. (2013) source

In the paper

“Extraction yields at optimal MAE parameters obtained by mathematical optimization (temperature 50.58°C, an liquid/solid ratio 24.39 ml g -1 , extraction time 43.50 min) were higher than that obtained by UAE (Wang et al. 2017b).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wang et al. 2017b

In the paper

“Recently, polar NADES have been applied to form aqueous biphasic systems (ABS) for the extraction of proteins (Zeng et al. 2014;Xu et al. 2015;Li et al. 2016;Zhang et al. 2016).”

What the sources say

• ?Not checked — no full text of the sourcecites Zeng et al. 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al. 2015
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Li et al. 2016

In the paper

“Moreover, the molar ratio affected the toxicity of certain NADES (e.g.ChAc:urea, ChCl:citric acid, ChCl:malic acid) (Paiva et al. 2014;Radošević et al. 2016b;Wen et al. 2015).”

What the sources say

• ?Not checked — no full text of the sourcecites Paiva et al. 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Radošević et al. 2016b
• ?Not checked — no full text of the sourcecites Wen et al. 2015 source

In the paper

“NADES extractions are often combined with ultrasound-(UAE) and microwaveassisted (MAE) technologies (Table 3).”

In the paper

“Penetration of NADES into the matrix can be improved by the heat generated during UAE and MAE.”

In the paper

“In the majority of mentioned studies, an extraction temperature of 50°C or lower was shown to be optimal.”

In the paper

“This kind of extractions (ball mill and mechanochemical extraction) demonstrated excellent extraction efficiency compared to the conventional solvents within a very short extraction time.”

What the sources say

• ?Not checked — no full text of the sourcecites Wang et al. 2016 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wang et al. 2017a

In the paper

“By comparing the toxicity of ChCl-and ChAc based NADES, Wen et al. (2015) concluded that the nature of the salt also had the influence on NADES toxicity.”

What the sources say

• ?Not checked — no full text of the sourcecites Wen et al. (2015) source

In the paper

“Intrinsic cell sensitivity presents only one factor for potential toxicity.”

In the paper

“However, despite the promising results obtained in the extraction of proteins, the NADES stability in the aqueous media were not addressed in these papers.”

In the paper

“Moreover, this study showed that intermolecular interaction between the selected NADES and tocols, allowed selective separation of individual tocols in palm oil, where products with fractions rich in tocotrienols and low in tocopherols (particularly α-tocopherol) were favorable.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ng et al. (2015)

In the paper

“In general, heretofore studies have indicated that NADES toxicity is predominantly related to the chemical nature of NADES, being a function of the hydrogen bonding.”

In the paper

“Ng et al. (2015) achieved optimal conditions for liquid-liquid extraction of tocols from palm oil by using choline chloride-malic acid as extraction solvent.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ng et al. (2015)

In the paper

“Several studies demonstrated that the presence of organic acids in NADES increased the deleterious effects (Hayyan et al. 2013;2016;Paiva et al. 2014;Radošević at al. 2016a;2016b).”

What the sources say

• ?Not checked — no full text of the sourcecites Hayyan et al. 2013 source
• ?Not checked — no full text of the sourcecites Paiva et al. 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Radošević at al. 2016a

In the paper

“while Radošević et al. (2015) found similar observation in the case of ChCl:oxalic acid NADES on two cell lines.”

What the sources say

• ?Not checked — no full text of the sourcecites Radošević et al. (2015) source

In the paper

“On the contrary, Wen et al. (2015) observed that investigated NADES exhibited lower phytotoxicity in comparison to their individual components.”

What the sources say

• ?Not checked — no full text of the sourcecites Wen et al. (2015) source

In the paper

“An example was reported by Dai, Verpoorte, and Choi (2014), who reported enhanced stability of carthamin (C-glucosyl quinochalcone), a red pigment in safflower, and a safflower extract in sugar based NADES in comparison to their stability in water or 40% ethanol under different light and temperature conditions, and storage duration.”

What the sources say

• ?Not checked — no full text of the sourcecites Dai, Verpoorte, and Choi (2014) source

In the paper

“Qi et al. (2015) were the first to study negative pressure cavitation extraction (NPCE) combined with NADES.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Qi et al. (2015)

In the paper

“The application of betaine NADES for the palm oil deacidification was demonstrated to be successful alternative to the process traditionally performed by steam stripping, which causes the loss of the majority of palm oil's natural antioxidants due to high temperature (Zahrina et al. 2018).”

What the sources say

• ?Not checked — no full text of the sourcecites Zahrina et al. 2018 source

In the paper

“Wei et al. (2015b) found the optimal conditions for the MAE assisted simultaneous extraction of four target flavonoids from Radix Scutellariae to be: extraction temperature 60.4°C, solvent to solid ratio 20:1 mL g -1 and extraction time 11.75 min.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wei et al. (2015b)

In the paper

“The proposed extraction method using NADES improved the extraction efficiency in comparison to water and methanol (Bajkacz and Adamek 2017a).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bajkacz and Adamek 2017a

In the paper

“On the other hand, several studies demonstrated that NADES do not interfere with the analytical determination of solutes, offering the possibilities for solute analytical characterization without time-and cost-consuming purification steps.”

In the paper

“Hence, the use of conventional, hazardous and volatile organic solvents typical of the standard and official methods was successfully substituted with NADES.”

In the paper

“Efficient recovery of extracted flavonoids was achieved using a 30% water solution of acetylcholine chloride/lactic acid ratio (2:1) as an extraction solvent.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bajkacz and Adamek 2017a

In the paper

“However, Benlebna et al. (2018) demonstrated some adverse effects of the oral administration of a high dose of the extract from green coffee beans in NADES extract (betaine:glycerol, 1:2 mole ratio +10% (v/v) of water) in rats.”

What the sources say

• ?Not checked — no full text of the sourcecites Benlebna et al. (2018) source

In the paper

“One cannot extrapolate non toxicity of the individual ingredients to non-toxicity of the NADES.”

In the paper

“conducted comprehensive research on 17 types of NADES based on choline chloride, acetylcholine chloride, choline tartrate, betaine, and carnitine with different compositions in order to tailor a solvent with highest extraction efficiency for targeted flavonoids.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bajkacz and Adamek 2017a

In the paper

“Also, it was demonstrated that these solvents in most cases provide higher extraction efficiency in comparison to the conventional organic solvents.”

In the paper

“It was found that NADES composed of choline chloride and 1,4-butanediol and conditions such as water content of 32.89%, extraction temperature of 94°C, and the extraction time of 44.74 min gave the highest extraction yield obtained at optimal UAE conditions, higher”

What the sources say

• ?Not checked — no full text of the sourcecites Zhang and Wang (2017) source

In the paper

“As discussed above, bioactive components from agri-industrial sources can be recovered using NADES-mediated extraction technologies which follow the principles of green chemistry (Figure 1).”

In the paper

“Wen et al. (2015) found that not all NADES are highly biodegradable.”

What the sources say

• ?Not checked — no full text of the sourcecites Wen et al. (2015) source

In the paper

“Antimicrobial activity of NADES extracts provides the opportunity for the development of pharmaceutical formulations, such as a topical formulation for dermal candidiasis (Espino et al. 2019).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Espino et al. 2019

In the paper

“According to the obtained EC 50 values (98-516 mM), investigated NADES were classified as a harmful material.”

In the paper

“Jeong et al. (2017) determined significantly lower decline in the content of tea catechins extracted with NADES composed of betaine, glycerol, and D-(+)-glucose, 4:20:1 (BGG-4) after 21 days of storage in comparison with their content in the extracts obtained with conventional solvents.”

What the sources say

• ?Not checked — no full text of the sourcecites Jeong et al. (2017) source

In the paper

“Additionally, significant differences in activity were observed between investigated NADES.”

In the paper

“For the most other common NADES constituents such as sugars, organic acids and amino acids no toxicity profiles are known.”

In the paper

“Zhang and Wang (2017) found the optimal deep eutectic solvent-based ultrasound-assisted extraction conditions for extraction of polysaccharides from Chinese yam.”

What the sources say

• ?Not checked — no full text of the sourcecites Zhang and Wang (2017) source

In the paper

“There are only few reports which applied in vivo rat model methods to test the NADES toxicity.”