M.A. Dzhavakhyan Dr.Sc. (Pharm.), All-Russian Scientific Research Institute of Medicinal and Aromatic Plants (Moscow, Russia) E-mail: O.K. Pavelieva Student, All-Russian Scientific Research Institute of Medicinal and Aromatic Plants (Moscow, Russia)

Various extraction methods with the use of ethanol, ethers and acids are extensively employing in industry. Their use is associated with multi-stage utilization, the need to detect and remove the residual toxic solvents from the target product. Currently, the search for new extractants that meet the principles of "green chemistry", such as the use of renewable plant resources and alternative solvents, is relevant. Deep eutectic solvents (DES) are of interest for modern pharmaceutical technology as an alternative to traditional organic extractants. They are characterized by the formation of strong hydrogen bonds and, due to their extremely low vapor pressure, are widely used in polymer chemistry and synthetic organic chemistry. The prospects for their use are due to their low toxicity, biodegradability, the possibility of selective extraction of a specific substance and renewal of the extractant. In numerous works of foreign scientists, the results of studying the effect of DES on the yield of various groups of biologically active substances (BAS) from both dried and fresh plants are described. The extraction processes with deep eutectic solvents are based on the replacement of solvent molecules with biologically active substances with the cleavage of old hydrogen bonds and the formation of new ones. DES performed well both for the extraction of groups of compounds and for the selective extraction of individual biologically active molecules. At the same time, the use of DES is characterized by the complexity of the choice of the initial substances, the need to select their ratio, and the aggregation instability of some systems. This review presents data on the DES fabrication technology. The most common components, melting points of ready-made mixtures and information on their stability are noted. We analyzed the data on the toxicity of the resulting mixtures and their possible biological activity, since many components are primary metabolites. This review summarizes the existing data on the toxicity and extraction capacity of eutectic solvents over the past 20 years.

deep eutectic solvent
bioactive compound

  1. Chemat F., Vian M.A., Cravotto G. Green extraction of natural products: concept and principles. International Journal of Molecular Sciences, 2012; 13(7): 8615–8627.
  2. Paiva A. et al. Natural Deep Eutectic Solvents – Solvents for the 21st Century. ACS Sustainable Chemistry & Engineering, 2014; 2(5): 1063–1071.
  3. Smith E.L., Abbott A.P., Ryder K.S. Deep Eutectic Solvents (DESs) and Their Applications. Chemical Reviews, 2014; 114(21): 11060–11082.
  4. Abbott A.P. et al. Deep Eutectic Solvents Formed between Choline Chloride and Carboxylic Acids:  Versatile Alternatives to Ionic Liquids. Journal of the American Chemical Society, 2004; 126(29): 9142–9147.
  5. Dai Y. et al. Ionic Liquids and Deep Eutectic Solvents in Natural Products Research: Mixtures of Solids as Extraction Solvents. Journal of Natural Products, 2013; 76(11): 2162–2173.
  6. Tang B., Zhang H., Row K.H. Application of deep eutectic solvents in the extraction and separation of target compounds from various samples. Journal of Separation Science, 2015; 38(6): 1053–1064.
  7. Abbott A.P. et al. Novel solvent properties of choline chloride/urea mixtures. Chemical Communications, 2003; 1: 70–71.
  8. Imperato G. et al. Low-melting sugar–urea–salt mixtures as solvents for Diels–Alder reactions. Chemical Communications, 2005; 9: 1170–1172.
  9. Ilgen F.,König B. Organic reactions in low melting mixtures based on carbohydrates and l-carnitine -a comparison. Green Chemistry, 2009; 11(6): 848–854.
  10. Ilgen F. et al. Conversion of carbohydrates into 5-hydroxy-methylfurfural in highly concentrated low melting mixtures. Green Chemistry, 2009; 11(12): 1948–1954.
  11. Jhong H.-R. et al. A novel deep eutectic solvent-based ionic liquid used as electrolyte for dye-sensitized solar cells. Electrochemistry Communications - ELECTROCHEM COMMUN, 2009;11: 209–211.
  12. Abbott A.P. et al. Extraction of glycerol from biodiesel into a eutectic based ionic liquid. Green Chemistry, 2007; 9(8): 868–872.
  13. Hayyan M. et al. Assessment of cytotoxicity and toxicity for phosphonium-based deep eutectic solvents. Chemosphere, 2013; 93(2): 455–459.
  14. Hayyan M. et al. Are deep eutectic solvents benign or toxic? Chemosphere, 2013; 90(7): 2193–2195.
  15. Hou X.D. et al. Evaluation of toxicity and biodegradability of cholinium amino acids ionic liquids. PLoS One, 2013; 8(3): e59145.
  16. Frade R.F.M. et al. Toxicological evaluation of magnetic ionic liquids in human cell lines. Chemosphere, 2013;92(1): 100–105.
  17. Zhang Q. et al. Deep eutectic solvents: syntheses, properties and applications. Chemical Society Reviews, 2012; 41(21): 7108–7146.
  18. Dai Y. et al. Natural Deep Eutectic Solvents as a New Extraction Media for Phenolic Metabolites in Carthamus tinctorius L. Analytical Chemistry, 2013; 85(13): 6272–6278.
  19. Dai Y. et al. Tailoring properties of natural deep eutectic solvents with water to facilitate their applications. Food Chemistry, 2015; 187: 14–19.
  20. Bi W., Tian M., Row K.H. Evaluation of alcohol-based deep eutectic solvent in extraction and determination of flavonoids with response surface methodology optimization. Journal of chromatography. A. 2013; 1285: 22–30.
  21. Wibowo D., Lee C.-K. Nonleaching antimicrobial cotton fibers for hyaluronic acid adsorption. Biochemical Engineering Journal. 2010; 53(1): 44–51.
  22. Tang B., Park H.E., Row K.H. Preparation of chlorocholine chloride/urea deep eutectic solvent-modified silica and an examination of the ion exchange properties of modified silica as a Lewis adduct. Anal Bioanal Chem. 2014; 406(17): 4309–4313.
  23. Park H.E., Tang B., Row K.H. Application of Deep Eutectic Solvents as Additives in Ultrasonic Extraction of Two Phenolic Acids from Herba Artemisiae Scopariae. Analytical Letters. 2014; 47(9): 1476–1484.
  24. Xiong Z. et al. Ultrasound-assisted deep eutectic solvent as green and efficient media for the extraction of flavonoids from Radix scutellariae. New Journal of Chemistry. 2019; 43(2): 644–650.
  25. Qi X.-L. et al. Green and efficient extraction of bioactive flavonoids from Equisetum palustre L. by deep eutectic solvents-based negative pressure cavitation method combined with macroporous resin enrichment. Industrial Crops and Products. 2015; 70: 142–148.
  26. Tang B. et al. Deep Eutectic Solvent-Based HS-SME Coupled with GC for the Analysis of Bioactive Terpenoids in Chamaecyparis obtusa Leaves. Chromatographia. 2013; 4: 373–377.
  27. Duan L. et al. Comprehensive Evaluation of Deep Eutectic Solvents in Extraction of Bioactive Natural Products. ACS Sustainable Chemistry & Engineering. 2016; 4(4): 2405–2411.
  28. Gu T. et al. Deep eutectic solvents as novel extraction media for phenolic compounds from model oil. Chemical Communications. 2014; 50(79): 11749–11752.
  29. Wang M. et al. Fast environment-friendly ball mill-assisted deep eutectic solvent-based extraction of natural products. Journal of Chromatography A. 2016; 1443:262–266.
  30. Zhuang B. et al. Deep eutectic solvents as green media for extraction of flavonoid glycosides and aglycones from Platycladi Cacumen. Journal of Pharmaceutical and Biomedical Analysis. 2017; 134:214–219.
  31. Wang M. et al. Ecofriendly Mechanochemical Extraction of Bioactive Compounds from Plants with Deep Eutectic Solvents. ACS Sustainable Chemistry & Engineering. 2017; 5(7): 6297–6303.
  32. Nadia J. et al. Approach for Polygodial Extraction from Pseudowintera colorata (Horopito) Leaves Using Deep Eutectic Solvents. ACS Sustainable Chemistry & Engineering, 2018; 6(1): 862–871.
  33. Ozturk B., Esteban J., Gonzalez-Miquel M. Deterpenation of Citrus Essential Oils Using Glycerol-Based Deep Eutectic Solvents. Journal of Chemical & Engineering Data. 2018; 63(7): 2384–2393.
  34. Obluchinskaya E.D., Daurtseva A.V.; Pozharitskaya O.N.; Flisyuk E.V.; Shikov A.N. Natural deep eutectic solvents as alternatives for extracting phlorotannins from brown algae. Pharm. Chem. J. 2019; 53: 243–247. [ 10.1007/ s11094-019-01987-0].
  35. Zhao, B.-Y.; Xu, P.; Yang, F.-X.; Wu, H.; Zong, M.-H.; Lou, W.-Y. Biocompatible deep eutectic solvents based on choline chloride: characterization and application to the extraction of rutin from Sophora japonica. ACS Sustain. Chem. Eng. 2015; 3: 2746–2755. [].
  36. Tang W., Li G., Chen B., Zhu T., Row K.H. Evaluating ternary deep eutectic solvents as novel media for extraction of flavonoids from Ginkgo biloba. Sep. Sci. Technol. 2016; 52:91–99. [].