Natural Deep Eutectic Solvents in Bioactive Compound Extraction

Natural deep eutectic solvents (NADES) have emerged as a transformative class of green solvents formed by mixing naturally derived hydrogen bond donors and acceptors to produce eutectic mixtures with melting points far below those of their individual components. Their unique physicochemical properties—adjustable polarity, low volatility, high thermal stability and enhanced solvation capacity—make them ideally suited to extract diverse bioactive compounds from plant and algal matrices. Unlike conventional organic solvents, NADES can be prepared from biodegradable, non‐toxic constituents such as sugars, organic acids and amino acids, offering an environmentally benign and cost‐effective alternative. By tailoring the molar ratio of components and water content, researchers can fine‐tune solvent viscosity and hydrogen‐bonding networks to improve selectivity and yield for polyphenols, flavonoids, alkaloids and other secondary metabolites. These features have accelerated the development of sustainable extraction processes for the food, pharmaceutical and cosmetic industries, with growing interest in scale-up and integration with techniques such as ultrasound‐assisted or microwave-assisted extraction. Global significance stems from reduced solvent waste, lower energy consumption and compatibility with circular bioeconomy principles, while ongoing studies explore NADES reuse, downstream purification and application in nutraceutical and therapeutic formulations.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Research from all publishers

Ultrasonic-assisted extraction combined with a choline chloride–malic acid NADES has been shown to extract hydroxytyrosol from olive leaves with remarkable efficiency. Optimisation of NADES concentration, extraction time and solid–liquid ratio delivered improved antioxidant, bacteriostatic and anti-inflammatory performance compared with aqueous controls, while density functional theory and spectroscopic analyses elucidated the molecular interactions between solvent and target compound.

An investigation into simultaneous recovery of hydrophilic (ascorbic acid, phlorotannins) and lipophilic (fucoxanthin) constituents from the brown alga Fucus vesiculosus demonstrated that NADES composition and sonication parameters can induce synergistic antioxidant effects. The addition of water to the NADES and extended ultrasound time produced extracts with over two-fold enhancement in radical-scavenging activity compared with conventional maceration, highlighting the capacity of tailored eutectic mixtures to stabilise and preserve multiple classes of bioactives during extraction and storage.

A greener strategy for anthocyanin extraction from blackberry using various NADES formulations revealed that acidic NADES yielded significantly higher total phenolic and flavonoid contents than methanol and ethanol. The recovery efficiencies for key anthocyanins such as cyanidin-3-glucoside and pelargonidin-3-glucoside were maximised by adjusting NADES viscosity and pH, underscoring the importance of hydrogen-bond donor and acceptor selection in targeting specific phytochemical profiles.

Natural Deep Eutectic Solvents in Bioactive Compound Extraction publication trend

The graph below shows the total number of articles in natural deep eutectic solvents in bioactive compound extraction across all publications each year (not limited to Nature Index journals).

Technical terms

Natural deep eutectic solvent (NADES): A mixture of naturally occurring compounds that forms a eutectic system with a melting point lower than its individual components, used as a green extraction medium.

Eutectic point: The specific composition at which the combined melting temperature of two or more components reaches its minimum.

Hydrogen bond donor (HBD) and acceptor (HBA): Chemical species in NADES that form hydrogen bonds, where HBDs provide hydrogen atoms and HBAs accept them, creating a network that dissolves target compounds.

Viscosity: A measure of a fluid’s resistance to flow, which influences mass transfer rates during extraction and can be tuned by water addition.

Polarity: The distribution of electrical charge within a solvent molecule, determining its affinity for polar or non-polar bioactive compounds.

References

1. Ultrasonic assisted natural deep eutectic solvents as a green and efficient approach for extraction of hydroxytyrosol from olive leaves. Industrial Chemistry and Materials (2024).
2. Efficacy of Natural Deep Eutectic Solvents for Extraction of Hydrophilic and Lipophilic Compounds from Fucus vesiculosus. Molecules (2021).
3. Greener extraction of anthocyanins and antioxidant activity from blackberry (Rubus spp) using natural deep eutectic solvents. LWT (2022).
4. Green solvents for the extraction of bioactive compounds from natural products using ionic liquids and deep eutectic solvents. Current Opinion in Food Science (2019).
5. Natural Deep Eutectic Solvents (NADES): Phytochemical Extraction Performance Enhancer for Pharmaceutical and Nutraceutical Product Development. Plants (2021).
6. Natural Deep Eutectic Solvents (NADESs) Combined with Sustainable Extraction Techniques: A Review of the Green Chemistry Approach in Food Analysis. Foods (2022).
7. Deep Eutectic Solvents for the Extraction of Bioactive Compounds from Natural Sources and Agricultural By-Products. Applied Sciences (2021).