Both the equilibrium simulation and REUS along the adsorption/desorption pathway for sorgoleone and precursors indicate that these molecules can freely insert into the membrane with no energy barrier. While we did observe membrane crossing events during our equilibrium simulations (Fig. , Table ), the number of events is not statistically significant on their own. Thus, we supplement these simulations with additional REUS simulations to sample along the leaflet exchange coordinate, moving the quinone head group along distance based reaction coordinates from one leaflet of the membrane to another leaflet. Since this reaction coordinate was sampled with two molecules moving to the midplane, creating a symmetric profile, Figure only reports free energies and diffusivities from the membrane midplane at 0 to the outer edge of the membrane at 25 Å.