Natural deep eutectic solvents for the separation of plant phenolic compounds: Recent advances and mechanistic insights

Natural deep eutectic solvents (NADES) have emerged as promising green media for separating plant-derived phenolic compounds, including polyphenols, flavonoids, and phenolic acids. These compounds possess strong antioxidant and anti-inflammatory activities, yet traditional organic solvent extraction often suffers from high energy demand, low selectivity, and degradation of active components. Recent studies show that NADES achieve efficient and selective separation through synergistic mechanisms such as extensive hydrogen bonding, polarity matching, and ion-π interactions. Their weak acidity and low water activity help prevent oxidation, thereby maintaining phenolic bioactivity while improving extraction efficiency. Process-intensification techniques, especially ultrasound, further mitigate viscosity-induced mass-transfer limitations. However, challenges remain, including high viscosity, nonspecific interactions with complex matrices, and limited molecular-level understanding. Future work should establish rapid solvent-screening frameworks based on molecular descriptors and integrate spectroscopic and molecular simulation tools to support the industrial application of NADES in green phenolic separation.