Deep Eutectic Solvents Selection for the Extraction of Phlorizin from <i>Malus hupehensis</i> Using Conductor‐like Screening Model for Real Solvents

Deep eutectic solvents (DESs), composed of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs), are efficient and widely applied solvents for extracting active compounds. Phlorizin (PHL), as the main component of Malus hupehensis, plays a critical role in the preparation of a DES-based extract. The appropriate option of DES is a primary consideration in the extraction of PHL from M. hupehensis. According to the chemical structural characteristics of PHL and solvent, the conductor-like screening model for real solvents is applied to select a DES. Lactic acid (LA) and betaine (BET) with a molar ratio of 2:1 and 40 wt% water are determined, and the extraction results are consistent with the predicted solubility of PHL in selected DESs. Thus, the optimal extraction conditions are identified as liquid-material ratio 40 mL/g, extraction time 50 min, and extraction temperature 60°C, resulting in the maximum yield of 14.07 ± 0.14%. As evidenced by Fourier-transform infrared and proton nuclear magnetic resonance spectra, PHL acts as an HBD and competitively interacts with HBA sites that are occupied by LA. Molecular dynamics simulations demonstrate the hydrogen bonding interactions between PHL and DES, consisting of LA and BET, with the lowest interaction energy of -135.6 kJ/mol. Therefore, the conductor-like screening model for real solvents is an available strategy to rapidly and efficiently select the appropriate DES on the basis of the thermodynamic characteristics. DESs can effectively extract PHL from M. hupehensis, and the DES-based extract of M. hupehensis with antioxidant activity provides a foundation for further application of DESs.