Are Natural Deep Eutectic Solvents the Missing Link in Understanding Cellular Metabolism and Physiology?
Open accessAbstract
Over the past decade, metabolomics has developed into a major tool for studying the metabolism of organisms and cells, and through this approach much has been learned about metabolic networks and the reactions of organisms to various external conditions (Lay et al., 2006). Most of this work involves a number of chemometric methods to identify markers in the metabolomic data for various events. But in fact, little work has been done on understanding the meaning of the metabolomic data itself and the role of the total of the compounds observed. Is there any logic in the studying the combination of compounds itself, instead of looking at the correlations between the compounds observed and any disease or applied experimental conditions? NMR-based metabolomics in particular give a clear view of the major compounds present in an organism or cell and enable the direct quantitative comparison of all major compounds. Considering all the information we have collected in recent years using our protocol for NMR-based metabolomics (Kim et al., 2010), we asked ourselves why a few very simple molecules are always present in considerable amounts in all microbial, mammalian, and plant cells. It seems that these compounds must serve some basic function in living cells and organisms. These compounds include sugars, some amino acids, choline, and some organic acids such as malic acid, citric acid, lactic acid, and succinic acid. With the exception of sugars, which may serve as storage products and a source of energy, the other compounds are present in such large amounts that it does not make sense to consider them as only intermediates in metabolic pathways.
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NADES were suggested as solvents for protein and DNA stabilization.
“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).”
From The perspectives of natural deep eutectic solvents in agri-food sector (2020) · cites this paper as Choi et al. 2011
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)
Experimental — accuracy not yet measuredPhysicochemical properties of NADES (viscosity, conductivity, density, and polarity) affect their end-use.
“The physicochemical properties of the NADES (viscosity, conductivity, density and polarity) affect their end-use (Choi et al. 2011;Dai et al. 2013b).”
From The perspectives of natural deep eutectic solvents in agri-food sector (2020) · cites this paper as Choi et al. 2011
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)
Experimental — accuracy not yet measuredNADES were first described by Choi et al. (2011) as a third class of liquids present in living cells, different from water and lipids, that serve as an alternative medium for biosynthesis, transport, and storage of compounds with intermediate polarity.
“Natural deep eutectic solvents (NADES) are firstly described by Choi et al. (2011) as a third class of liquids present in living cells, different from water and lipids, that play an important role as an alternative medium for biosynthesis, transport and storage of compounds with intermediate polarity.”
From The perspectives of natural deep eutectic solvents in agri-food sector (2020) · cites this paper as Choi et al. (2011)
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredNADESs are even more environmentally friendly than DESs due to their natural origin.
“Besides all the advantages of DESs, NADESs are even more environmentally friendly due to their natural origin [13].”
From Application of deep eutectic solvents in analytical chemistry. A review (2017) · cites this paper as [13]
The paper’s concluding discussion (page not specified in our copy) describes NADES as natural, nontoxic, sustainable, and environmentally friendly. It presents them as alternatives to toxic synthetic ionic liquids, but does not say they are more environmentally friendly than DESs or establish that comparison on the basis of natural origin. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNatural deep eutectic solvents (NADESs) were introduced into analytical practice as an alternative type of extraction solvent.
“Recently, natural deep eutectic solvents (NADESs) were introduced into analytical practice as an alternative type of extraction solvent.”
From Application of deep eutectic solvents in analytical chemistry. A review (2017) · cites this paper as [13]
The paper introduces NADES and identifies extraction as a potential use. It does not say they had been introduced into analytical practice as extraction solvents; it presents that application as a possibility, not an established practice. (LLM, conf=0.86)
Experimental — accuracy not yet measured
NADESs have been proposed as an alternative to ILs/DESs because their ingredients come from nature and they are believed to have a real physiological or biological role in nature.
“Natural DESs or ILs, known as NADESs, have been proposed as a different alternative for two reasons: their ingredients are sourced from nature and they are believed to have a real physiological or biological role in nature.”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
NADESs are mixtures of natural compounds (organic acids/bases, amino acids, sugars, sugar alcohols, polyalcohols) that interact via hydrogen bonding and liquefy at specific molar ratios.
“Natural deep eutectic solvents (NADESs) are mixtures of natural compounds, namely, organic acids and bases, amino acids, sugars, sugar alcohols, and polyalcohols that interact through hydrogen bonding and liquefy if combined in specific molar ratios.”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
The nectar of Cleome hassleriana contains sucrose, glucose, and fructose as major components in practically equimolar ratios.
“an NMRbased metabolomic study of the nectar of Cleome hassleoriana showed the presence of sucrose, glucose, and fructose as major components in practically equimolar ratios.”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
NADESs have a protective role on proteins.
“The protective role of NADESs on proteins has also been proved [1]”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
Enzymes in NADES solution are activated by dilution with water.
“as well as the activation of enzymes in an NADES solution by dilution with water [1,11].”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
In barley seed aleurone tissue, sucrose and choline were the major low-mass molecules and were present in approximately equimolar amounts.
“In one case, the analysis of the aleurone tissue of barley seeds (Hordeum vulgare) by 1 H NMR spectroscopy showed that the major low mass molecules were sucrose and choline and that they were present in approximately equimolar amounts.”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
Maple syrup consists mainly of sucrose and malic acid.
“The analysis of a plant sap, maple syrup (Acer spp.), showed that it consists mainly of sucrose and malic acid”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
1H NMR metabolomic analyses showed common metabolites such as sucrose, glucose, fructose, malic acid, lactic acid, choline, and betaine at high levels and with similar intensity signals across biological materials.
“This evidence was based on 1 H NMR metabolomic analyses that showed the presence of common metabolites like sucrose, glucose, fructose, malic acid, lactic acid, choline, and betaine at high levels and with similar intensity signals in all kinds of the biological material.”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
Drought, desiccation, and cold resistance are always connected with high levels of osmolytes, and osmolytes include all compounds found to form NADESs.
“For example, drought, desiccation, and cold resistance are always reported to be connected with a high level of osmolytes.Osmolytes encompass all the compounds found to form NADESs [1].”
From Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents (2018) · cites this paper as [1]
NADES were introduced when cellular constituents like fructose, glucose, citric acid, proline, and other metabolites formed a viscous liquid at defined molar ratios.
“NADES were introduced when cellular constituents like fructose, glucose, citric acid, proline, and other metabolites formed a viscous liquid at defined molar ratios [41].”
From Recent Advances in Hydrophobic Deep Eutectic Solvents for Extraction (2019) · cites this paper as [41]
Natural deep eutectic solvents (NADES) can be obtained using abundant natural compounds as DES precursors, including organic acids, sugars, amino acids, and choline derivatives.
“Natural deep eutectic solvents (NADES) can be obtained using abundant natural compounds as DES precursors, including organic acids, sugars, amino acids, and choline derivatives [14].”
From Greenness of procedures using NADES in the preparation of vegetal samples: Comparison of five green metrics (2022) · cites this paper as [14]
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“NADES were introduced when cellular constituents like fructose, glucose, citric acid, proline, and other metabolites formed a viscous liquid at defined molar ratios [41].”
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- Authors
- Choi, Y. H., van Spronsen, J., Dai, Y., Verberne, M., Hollmann, F., Arends, I. W. C. E., Witkamp, G.-J., & Verpoorte, R.
- Affiliations
- Leiden University (NL)
- Natural Products Laboratory, Institute of Biology (Y.H.C., Y.D., M.V., R.V.), Leiden University, 2300 RA Leiden, The Netherlands; and Laboratory for Process Equipment (Y.H.C., J.v.S., G.-J.W.) and Biocatalysis and Organic Chemistry Group, Department of Biotechnology (F.H., I.W.C.E.A.), Delft University of Technology, 2628 CA Delft, The Netherlands
- ORCID
- Venue
- Plant Physiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-08-01
- Volume
- 156
- Issue
- 4
- Pages
- 1701-1705
- ISSN
- 0032-0889 (ISSN-L)
- 1532-2548
- PMC
- PMC3149944
- OpenAlex
- W2036206077
- Cited by
- 1,368
- References
- 24
- Citations by year
- 2026: 142 · 2025: 168 · 2024: 168 · 2023: 154 · 2022: 147 · 2021: 132 · 2020: 120 · 2019: 98 · 2018: 55 · 2017: 56 · 2016: 42 · 2015: 34 · 2014: 17 · 2013: 19 · 2012: 15
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- PLANT PHYSIOLOGY (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemical Engineering › Catalysis › Ionic liquids properties and applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- natural deep eutectic solvents, NMR metabolomics, cellular metabolism, metabolite composition, sugar, amino acids, choline, organic acids, malic acid, citric acid, lactic acid, succinic acid, metabolic networks
- MeSH terms
- Rutin, Solubility, Solvents, Nuclear Magnetic Resonance, Biomolecular, Cleome, Laccase, Ionic Liquids, Plant Cells
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