Design of a pH-switchable supramolecular deep eutectic solvent for the extraction of flavonoids from citrus peel waste and Rutaceae herbs.

The rising demand for natural ingredients across the food, cosmetics, healthcare industries has driven the broader utilization of agricultural and food industry waste as valuable sources of bioactive compounds. A pH-switchable supramolecular deep eutectic solvent (SS-DES) based on geraniol and octanoic acid was first prepared for the simple, rapid, and efficient extraction of flavonoids from citrus peel waste and Rutaceae herbs. In this system, geraniol acted as a hydrophobic building block to construct the hydrophobic SS-DES, thereby effectively resolving the poor compatibility between conventional hydrophilic DESs and lipophilic flavonoids. Furthermore, the application of SS-DES overcame the drawbacks of difficult phase separation, excessive solvent consumption, and low reusability. A series of DESs were successfully prepared, and the key experimental parameters affecting enrichment were systematically investigated and optimized. Among these DESs, the geraniol/octanoic acid (1,1) system containing (2,6-di-O-methyl)-β-cyclodextrin showed the highest enrichment for flavonoids and was successfully applied to citrus peel wastes and Rutaceae medicinal herb samples. The prepared SS-DES was characterized using FT-IR and 1H NMR. Meanwhile, the extraction mechanism of target compounds using the SS-DES were investigated via molecular docking and density functional theory (DFT) calculations. Furthermore, following an evaluation of the environmental impact of the proposed method, the biocompatibility of the SS-DES was further evaluated by in vitro cytotoxicity assays in GES-1 and HK2 cell lines, as well as in vivo acute oral toxicity test. After five adsorption-desorption cycles using AB-8 macroporous resin, the extraction performance of the regenerated SS-DES remained above 91.72%, indicating had satisfactory stability reusability. As a result, the designed SS-DES may hold great potential to replace traditional organic solvents for extracting flavonoids from diverse and complex matrices.