Density Functional Theory with Implicit Solvents for Accurate Estimation of Aqueous and Organic Solvation Free Energies of Lignin Fragments

Lignin is the main potential source of renewable aromatic chemicals, and solvation free energy (delta G(solv)) is a fundamental thermodynamic parameter for a compound in solution. Here, density functional theory with the electron density-based continuum solvent model (SMD-DFT) is employed to calculate delta G(solv) for 283 neutral lignin depolymerization fragments and analogues (LDF & A) in water and organic solvents (1-octanol, cyclohexane, methyl-isobutyl ketone, and butyl acetate). Calculations for LDF & A are challenging due to the balance of hydrophilic oxygenations and hydrophobic aromatic rings with pi orbitals. After correction of atomic van der Waals radii, calculated delta G(solv) in water for a subset of 18 aromatic monomers is shown to outperform the accuracy of the FreeSolv benchmark. For organic solvents, comparisons through partition coefficients (log P) from several public datasets reveal that SMD-DFT calculations can accurately predict log P after accounting for systematic biases due to solvent admixtures not considered by the calculations. The presented results for LDF & A demonstrate that SMD-DFT provides useful estimates for log P and unprecedented accuracy for aqueous delta G(solv). The obtained datasets of aqueous and organic delta G(solv) for LDF & A provide a key advancement toward accurate computer modeling of lignin processing into renewable fuels and chemicals.