Exploring the physicochemical properties of amygdalin in selected solvents: Insights from molecular simulation

Amygdalin, a cyanogenic glycoside with anticancer and pain-relief properties, faces extraction challenges due to toxic solvents and degradation risks. To predict solubility and solvation mechanisms, we investigated amygdalin's solvation free energy in a range of solvents using molecular simulations. We found a solvation strength hierarchy: dimethyl sulfoxide > acetone > ethyl acetate > water > THF > ethanol > methanol > octanol > dichloromethane > toluene. We found that both Coulombic and van der Waals interactions significantly influence solvation. Radial distribution functions and connection matrices confirmed hydrogen bonding and hydrophobic interactions. Spatial and combined distribution functions revealed specific orientations of the tetrahydrofuran and toluene rings and amygdalin's phenyl group. At distances > 600 pm, rings are antiparallel; at < 600 pm, parallel-displaced and perpendicular orientations were observed. These findings facilitate the development of efficient and sustainable amygdalin extraction methods for medical applications, providing a foundation for future research aimed at optimizing extraction protocols and exploring novel therapeutic applications. • Cavity formation free energy rises with solvent self-association strength. • Favorable LJ (or vdW) and Coulombic solute-solvent interactions are important for solvation. • Amygdalin solvation in toluene is driven by π − π interactions.