Using REUS calculations, we can quantify this specifically, measuring an energetic difference of ∼ 13 kcal/mol between the adsorbed and desorbed states. Previously it has been reported that phospholipids featuring two acyl chains and thus approximately double the hydrophobic interactions pay a ∼ 20 kcal/mol price to desorb, and fatty acid compound with one acyl chain encounter a barrier around ∼ 10 kcal/mol. The difference of around 3 kcal/mol in additional cost to desorb a sorgoleone from the membrane may be an effect of membrane composition, or potentially additional hydrophobic bulk offered by the quinone headgroup, as the desorption cost for a lipophillic molecule is driven by hydrophobic bulk. Regardless, much of the cost to desorbing sorgoleone clearly represents the effect of drawing the acyl tails into an aqueous solvent environment.