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 (ΔGsolv) 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 ΔGsolv 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 π orbitals. After correction
of atomic van der Waals radii, calculated ΔGsolv 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 ΔGsolv. The
obtained datasets of aqueous and organic ΔGsolv for LDF&A provide a key advancement toward accurate
computer modeling of lignin processing into renewable fuels and chemicals.