Development of Hydrophobic Deep Eutectic Solvents’ Reviewed in New Paper

A review published by scientists from Hangzhou Normal University and led by Weiyang Tang provided an overview of the history and development of hydrophobic deep eutectic solvents (hDESs), which are multicomponent designer solvents that avoid mixing with water (1). Their findings were published in the Journal of Chromatography A (2).

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In 2003, deep eutectic solvents (DESs) were discovered. These are homogenous and transparent mixtures created by combining over two components in a specific molar ratio under certain conditions. They are referent to ionic liquids (ILs), as they have several similar properties, such as wide liquidus range, low volatility, and high solvation ability (3). Moreover, DESs are well-regarded for their chemical stability, non-flammability, and biodegradability; further, their properties can be altered by adjusting the combination of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs). With green chemistry becoming a popular approach to analytical chemistry in the past 20 years, DESs has proven an effective development towards being more energy-efficient and environmentally friendly.

Early DES research focused on hydrophilic DES; however, these solvents typically exhibit poor stability and decompose in water due to hydrogen bonds forming. This makes hydrophilic DESs limited in applications like liquid-phase extraction, which requires high alkalinity and low water content. To address this, dispersants or emulsifiers are often added, though this can result in reduced environmental friendliness and increased laboratory hazards.

Hydrophobic DESs (hDESs), which are immiscible with water, were created to address the challenges that come from typical DESs. While hDESs are effective in different ways, they also come with their own set of challenges, and both the positive and negative factors of each type of DESs should be considered when setting up an experiment.

In this review article, the scientists summarized the work done on hDESs development, including the latest research progress regarding their applications, extraction techniques, and recycling methods. Additionally, it hints at issues that need to be addressed in the future.

Advantages

Using hDESs can facilitate the extraction and separation of various non-polar target compounds from aqueous solutions. They can also be suitable mediums for the dissolution and delivery of non-polar drugs. hDESs possess numerous advantages, such as their high density, strong hydrophobicity, low toxicity, and simple preparation, among other properties.

More iterations have been developed, offering unique advantages and wide applicability as extraction and separation media, such as sufficient efficiency for hydrophobic natural products and satisfactory phase separation capability in aqueous substrates. Additionally, hDESs solve the issue of poor extraction efficiency of traditional hydrophilic DESs for lipophilic natural products. This has promoted the commercial applications of DESs in the field of natural product extraction and separation.

Challenges

Though notable efforts have been made to improve hDESs, there are still several challenges that can inconvenience users. HDESs can face issues like high viscosity, turbidity, and difficulty in phase separation during liquid-phase extraction. The toxicity, vapor pressure, and bioavailability require further investigation, and traditional organic solvents like methanol and chloroform are less expensive compared to the terpenes and organic acids used for preparing hDESs. As such, studying the reuse and recycling of hDESs is critical.

Additionally, there are currently no systematic standards or testing methods to evaluate the toxicological behavior and degradation of hDESs. Research groups have retained mixed results, inferring that the components of some hDESs vary and are case-dependent. Rapid and accurate toxicological evaluation methods must be created, and researchers should also explore hDESs biodegradation mechanisms to ensure their safety for long-term use.

It is crucial to develop novel hDESs, such as designing hDESs with specific properties by introducing functional groups or modulating intermolecular interactions, as well as developing new types of DESs which can switch between hydrophilicity and hydrophobicity through inducible factors. HDESs should also be separated from natural products using efficient and low-energy consumption technologies, and combining multiple DESs can be a new strategy for improving extraction efficiency by achieving separation extraction and separation of natural products with different properties.

Hydrophobic DESs are a viable alternative for replacing organic solvents in liquid-liquid extraction (LLE) or powder extraction. However, there is still more work to be done to enable routine application of DESs-based extraction technologies in industrial settings. To meet current global environmental protection standards, it is necessary to develop environmentally friendly and efficient green extraction and separation technologies. Therefore, designing and developing various new DESs is a crucial process.

References

(1) Devi, M.; Moral, R.; Thakuria, S.; et al. Hydrophobic Deep Eutectic Solvents as Greener Substitutes for Conventional Extraction Media: Examples and Techniques. ACS Omega 2023, 8 (11), 9702–9728. DOI: 10.1021/acsomega.2c07684

(2) Zheng, X.; Yin, F.; Gong, G.; et al. An Overview of Hydrophobic Deep Eutectic Solvents Driven Liquid-Phase Extraction: Applications and Prospects. J. Chromatogr. A 2025, 1748, 465824. DOI: 10.1016/j.chroma.2025.465824

(3) Deep Eutectic Solvent. ScienceDirect 2023. https://www.sciencedirect.com/topics/chemistry/deep-eutectic-solvent (accessed 2025-3-19)