However, unlike previous studies for lignin where the small molecules are reasonably water soluble, the partition coefficients inferred from our simulations are larger and positive, indicating that sorgoleone or its precursors are over a billion-fold enriched in the membrane relative to aqueous solution (Table ). From the permeability calculation, we observe that the rate limiting step from passive permeation of the sorgoleone and its precursor molecules is the membrane extraction step, which is over a million times slower than exchange between leaflets.