Hydrophobic Natural Deep Eutectic Solvents for Extraction of Bioactive Compounds: Multiscale Characterization, Quantum Simulations, and Molecular Interaction Studies with Cry j 1 and Amb a 1 Allergens

This study explores the synthesis, characterization, and extraction efficiency of hydrophobic natural deep eutectic solvents (NADESs), along with the allergen-modulating potential of extracted bioactive compounds. Six NADESs were synthesized using binary combinations of camphor, thymol, eugenol, and menthol (1:1 molar ratio) and characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis and differential thermal analysis (TGA/DTA), density functional theory (DFT), and molecular dynamics simulations (MD simulations). Bioactive compounds were extracted from Thujopsis dolabrata wood biomass via ultrasonic-assisted extraction and analyzed using gas chromatography–mass spectrometry (GC–MS). The total essential oil yield, estimated semiquantitatively by summing the peak areas of key terpenoid compounds, ranged from 1.91% to 7.90% across different NADES systems, indicating their varied extraction capacities. Molecular docking was performed to assess their allergen-modulating interactions with Amb a 1 and Cry j 1. All NADESs exhibited single-stage decomposition (110–125 °C) except camphor–menthol, which recrystallized. FTIR and simulations confirmed strong hydrogen bonding in eugenol-based NADESs, particularly menthol–eugenol. Extraction identified 47 bioactive compounds, with 4,5α-Epoxy-3-methoxy-17-methyl-7α-(4-phenyl-1,3-butadienyl)-6β,7β-(oxymethylene) morphinan as the most abundant (9.31–11.16%). It exhibited the highest binding affinity (Cry j 1: −8.60 kcal/mol, Amb a 1: −7.40 kcal/mol) and lowest inhibition concentration (Cry j 1: 0.49 µM, Amb a 1: 3.74 µM), suggesting strong allergen-modulating potential. Hydrophobic interactions and hydrogen bonding drove protein–ligand binding. These findings highlight NADESs as effective, sustainable solvents for extracting bioactive compounds with allergen-modulating potential.