DFT-based insights into deep eutectic solvent-promoted arbutin extraction: Hydrogen-bonding and electrostatic analysis

The molecular basis of deep eutectic solvent (DES)-mediated extraction of arbutin was investigated using a computational chemistry method for the first time to uncover the impressionable chemical functionality of DESs. The hydrogen-bonding interactions among hydrogen bond acceptors, hydrogen bond donors, and arbutin were investigated based on density functional theory, through electrostatic potential (ESP) distribution, molecular polarity index (MPI), independent gradient model based on Hirshfeld partition (IGMH), and atoms-in-molecules (AIM) analyses. ChCl/LA (1:3) exhibited superior extraction efficiency for arbutin among the examined DESs. The ESP distribution matching study revealed that CA, LA, Gly, and PG displayed a higher overall charge distribution compatibility with ChCl than UR. In the DES–arbutin systems, ChCl/LA (1:3) showed its strongest and most stable binding characteristic with arbutin, as evidenced by the optimal electrostatic matching and the highest MPI value with arbutin. IGMH analysis indicated that both the hydroxyl and carboxyl groups in LA endowed a stronger hydrogen-bonding interaction between arbutin and ChCl/LA compared to that between arbutin and ChCl/Gly and ChCl/UR. This was further supported by the fact that the absolute value of the interaction energy of ChCl/LA (1:3) (−30.33 kcal/mol) was higher than those of other DESs (−15.86 to −26.26 kcal/mol). Moreover, AIM analysis revealed that the highest bond critical point (BCP) electron density of ChCl/LA (1:3)–arbutin was at BCP 236 (O 1 ···H 34 O) = 0.0488 a.u., corresponding to a hydrogen bond energy of −10.1534 kcal/mol, indicating the strongest hydrogen bond interaction. These findings provide a novel molecular-scale rationale for designing effective DESs for natural-product extraction.