Computationally guided amino acid-based deep eutectic solvents for one-pot nitrogen functionalization of lignin

Lignin valorization often faces barriers owing to its intrinsic structural heterogeneity, poor aqueous processability, and limited chemical reactivity. To address these obstacles, the conductor-like screening model for real solvents (COSMO-RS) was used to rationally design amino acid-based deep eutectic solvents (AADES) that enable one-pot lignin dissolution, chemical modification, and fractionation. High–throughput screening identified five AADES, and a streamlined process (solid/liquid ratio of 1:8; 100–130 °C; 2–4 h) with staged antisolvent precipitation yielded primary (LA) and secondary (LB) lignin fractions. A lysine-formic acid DES at 120 °C for 4 h yielded > 60 % recovery of the LB fraction, with the highest nitrogen (N) incorporation (2.66 wt% in bulk and 2.30 wt% at the surface) while largely preserving the aromatic lignin backbone. Spectroscopic analysis confirmed carbon–N bond formation via nucleophilic attack at the benzylic (Cα) position of lignin. The weight-average molecular weight of lignin decreased from 3773 to 2839 g mol −1 , with dispersity narrowing from 1.76 to 1.32, accompanied by increased phenolic hydroxyl groups and enhanced thermal stability (T max  = 355–360 °C). Overall, the nucleophilic nature of AADES suppresses lignin condensation while enabling selective N -functionalization, providing a solvent-selection strategy for scalable lignin valorization.