Rapid and Efficient Extraction of Chlorogenic Acid from Honeysuckle Using Microwave-Assisted Deep Eutectic Solvents: Process Optimization and Mechanistic Investigation via Integration of Experiments and Density Functional Theory Calculations

Chlorogenic acid (CA), the principal bioactive constituent of honeysuckle, is conventionally extracted by time-consuming methods using toxic organic solvents, which carry the risk of thermal degradation. This study provides a rapid and efficient microwave-assisted deep eutectic solvent (DES-MAE) method for CA extraction and elucidates its mechanism at the molecular level. Eight DESs were systematically screened, and extraction parameters were optimized via single-factor experiments and response surface methodology (RSM). Density functional theory (DFT) calculations were performed to reveal the DES-CA interaction mechanism. Benzyltrimethylammonium chloride–ethylene glycol with 40% water content was identified as optimal. Under the optimized conditions (640 W, 78 s, and 9.35 mg/mL), the quadratic model (R2 = 0.9879) predicted a CA yield of 39.851 mg/g, which was consistent with the experimental value of 39.431 ± 0.068 mg/g (1.1% relative deviation). DFT calculations revealed four hydrogen bonds and π-π stacking between DES1 and CA, with a binding energy of −25.641 kcal/mol, which far exceeded those of water (−5.277 kcal/mol) and ethanol (−8.946 kcal/mol). The DES-MAE method achieved the highest extraction yield within merely 78 s, compared with 60 min for HRE and 30 min for the pharmacopoeial method. This work provides a rapid, efficient, and mechanistically validated strategy for extracting bioactive compounds from traditional Chinese medicinal materials.