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What NADES are and why they can make the planet a better place

An irresponsible use of chemical processes for the mass production of consumer goods (such as pharmaceuticals, cosmetics or food) can provoke a huge environmental impact due to the high energy consumption required, the amount of resources needed and the release of harmful substances, namely Volatile Organic Compounds (VOCs) produced by certain solvents. VOCs are a group of reactive air pollutants prone to oxidation reactions, which are detrimental for air quality and can severely affect human health (e.g.: benzene, toluene, formaldehyde) [1].

Did you know?

About 807.000 tonnes of VOCs were emitted by the UK in 2017. Then, could this be considered as an acceptable level of emissions? Undoubtedly, it is a much smaller number than those reported during the last century but there is still a long way to go. Note that Figure 1 shows that one of the major contributor to VOC emissions comes from the use of solvents (depicted in lilac) [2]. This study was chosen as an example to understand better the situation with the VOCs as well as due to the clear and segmented graphical data.

Figure 1. Emission of VOCs in UK according to its different sources (1990-2017) and predictions for the next decade (2020-2030) [2].

What now?

Thus far, the use of environmentally friendly solvents is rather limited and has a number of drawbacks, such as the need of advanced and costly instrumentation or high energy requirements (e.g.: supercritical fluid extraction) [3], and it is therefore necessary to look for new processes that contribute to sustainable development. One of the ways to contribute to this goal is through the use of alternative solvents such as deep eutectic solvents.

Deep Eutectic Solvents (DES) are formed by the combination of a hydrogen bond acceptor species (HBA) and a hydrogen bond donor species (HBD), which can associate by hydrogen bridge interactions resulting in a mixture with a lower melting point than the two substances separately (See Figure 2).

Figure 2. Example of components of a eutectic mixture. A single molecule of choline chloride (HBA) interacts with two molecules of urea (HBD), establishing hydrogen bonds to form the DES in 1:2 proportion.

The formation of these mixtures is visually striking because when the solid components (HBA and HBD) are mixed in the right proportion, they become a liquid without the need of additional solvents (See Figure 3) [4].

Figure 3. Example of formation of a DES from two solid components that become a liquid phase (lower melting point) without the intervention of other solvents.

When the components of the mixture are primary metabolites (e.g.: aminoacids, sugars), they are called Natural Deep Eutectic Solvents (NADES) [5]. As they are made by compounds formed naturally by plants, they are inherently biodegradable and they have become a promising approach to obtain that are of high interest for the cosmetic as well as for the food and pharmaceutical industries.

The added value of NADES is based on the following characteristics (See also Figure 4) [6, 7]:

· Medium polarity, allowing them to dissolve a wide variety of substances.

· Non-volatile nature, which makes them potentially recyclable and decreases greatly the emission of VOCs.

· Improved extraction yields, being similar or higher than conventional organic solvents and with a lower environmental impact.

· Despite having high viscosity, they can be modified by increasing the heat during the extraction process, which also favours the diffusion and extraction yield with overall low energy requirements.

· Improved stability of the products due to the formation of hydrogen bonds between the NADES and the solute.

Figure 4. Summary of the main applications and benefits of the use of NADES.

The application of NADES in the cosmetic field has also been addressed. Some studies showed that extraction of anti-oxidant compounds [8] and colorants [9] with NADES yielded highly stable compounds with increased microbial safety, which make them compatible for cosmetic applications. Additionally, the enhanced bioavailability opens further paths to discover plant extracts that can result beneficial for the skin, contributing to the expansion and diversity of NADES.

Although some of them have been found to be safe in skin models (and can therefore be included in cosmetic formulations), not all NADES are allowed due to mandatory compliance with European Cosmetic Regulation [6]. Some examples of accepted mixtures are PMH (proline:malic acid) or LGH (lactic acid:glucose), provided that the allowed concentrations are used [8].

Due to their recent application as sustainable solvents, published studies on NADES are still scarce. Therefore, research on their recovery and resizing on an industrial scale will allow for a wider application of these compounds in the future [10].


  1. He, Z., et al., Contributions of different anthropogenic volatile organic compound sources to ozone formation at a receptor site in the Pearl River Delta region and its policy implications. Atmos. Chem. Phys., 2019. 19(13): p. 8801-8816.

  2. Lewis, A.C., et al., An increasing role for solvent emissions and implications for future measurements of volatile organic compounds. 2020. 378(2183): p. 20190328.

  3. Manjare, S.D. and K. Dhingra, Supercritical fluids in separation and purification: A review. 2019. 2(3): p. 463-484.

  4. Mbous, Y.P., et al., Applications of deep eutectic solvents in biotechnology and bioengineering-Promises and challenges. Biotechnol Adv, 2017. 35(2): p. 105-134.

  5. Choi, Y.H., et al., Are Natural Deep Eutectic Solvents the Missing Link in Understanding Cellular Metabolism and Physiology? Plant Physiology, 2011. 156(4): p. 1701-1705.

  6. Benoit, C., C. Virginie, and V. Boris, Chapter Twelve - The use of NADES to support innovation in the cosmetic industry, in Advances in Botanical Research, R. Verpoorte, G.-J. Witkamp, and Y.H. Choi, Editors. 2021, Academic Press. p. 309-332.

  7. Hikmawanti, N.P.E., et al., Natural Deep Eutectic Solvents (NADES): Phytochemical Extraction Performance Enhancer for Pharmaceutical and Nutraceutical Product Development. 2021. 10(10): p. 2091.

  8. Dai, Y., et al., Application of natural deep eutectic solvents to the extraction of anthocyanins from Catharanthus roseus with high extractability and stability replacing conventional organic solvents. Journal of Chromatography A, 2016. 1434: p. 50-56.

  9. Dai, Y., R. Verpoorte, and Y.H. Choi, Natural deep eutectic solvents providing enhanced stability of natural colorants from safflower (Carthamus tinctorius). Food Chemistry, 2014. 159: p. 116-121.

  10. Cvjetko Bubalo, M., et al., New perspective in extraction of plant biologically active compounds by green solvents. Food and Bioproducts Processing, 2018. 109: p. 52-73.

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