Thermodynamic and Atomistic Insights into Lignin Solubility from Experimentally Validated Molecular Dynamics Simulations

Lignin solubility is critical for extraction, tailoring processing, and downstream applications. Understanding the factors governing its solubility helps understand the behavior of this chemically heterogeneous aromatic biopolymer that has found increasing use in recent years. This study explores the molecular weight dependence of lignin solubility across different solvents. Molecular dynamics simulations are linked to experimental solubility measurements via a ranking of solvents. This integrated approach combines the strength of atomistic insights from simulations with experimental validation. The free energy of solvation and its enthalpic and entropic contributions are determined, and specific interactions such as hydrogen bonds and π-π stacking are quantified. The results show that differences in lignin solubilization efficiency between organic solvents and water are primarily enthalpy-driven with a smaller entropic contribution. In contrast to simplified solubility parameter approaches, molecular dynamics simulations provide a holistic view of lignin solubility and are shown to be a useful tool for understanding its solubilization mechanisms.