Thermodynamics-Informed Learning Captures Hierarchical Hydrogen-Bond Networks in Deep Eutectic Solvents

Yanpeng Ye, Chaoran Duan, Mian Xu, S. Mani Sarathy

Deep eutectic solvents (DESs) offer a tunable platform for lignocellulose refining, but their solvation behavior depends on multicomponent hydrogen-bond networks rather than individual constituent properties. We develop TiNN, a thermodynamics-informed neural network that hierarchically represents HBA-HBD association and solute accommodation through a learned free-energy pathway. Trained on 938 records, TiNN achieves a test-set $R^2$ of 0.917 and generalizes to new HBA-HBD combinations and sparse conditions. Ablation identifies solute-specific stabilization as the largest contributor to prediction accuracy, while the importance of hydrogen-bond compatibility depends on the dissolution mechanism. Experimental measurements of glucose, xylan, and Kraft lignin in acidic, basic, and neutral DESs show that TiNN reduces the geometric mean solubility error from more than 23-fold with COSMO-RS to approximately 1.5-fold. Without training on fractionation data, TiNN also distinguishes DES formulations with high and low lignin and hemicellulose removal from corn stover. These results support chemically grounded solvent screening for lignocellulose fractionation.