Sorgoleone and its precursors were observed to spontaneously integrate into the membrane from aqueous solution in equilibrium simulation. However, interleaflet transitions were sporadic, so transition counting methods to assess permeation were not feasible. REUS was performed to evenly sample along the adsorption/desorption pathway as well as the interleaflet transition pathway. These are each sampled with independent reaction coordinates, implemented using the colvars module 66 within NAMD. The observed barrier to interleaflet transitions are breaking interactions between the quinone headgroup and the surrounding environment featuring lipid headgroups and water. The hydrophobic sorgleone tails follow the headgroup. Thus, measuring progress for the interleaflet transition based strictly on the position of the quinone headgroup is appropriate. However, the primary barrier along the adsorption and desorption pathway are hydrophobic contacts between the lipid tails. Along this pathway, the key metric to track are contacts between the molecule of interest and the surrounding hydrophobic environment, with zero contacts representing the desorbed state.