Passive Transport across Cell Membranes beyond the Overton Rule: Insights from Solute Exchange in Vesicles and Molecular Dynamics of Atropisomers

atropisomer is properly described by the bind-flip mechanism, where the sulfonamide groups first approach the bilayer in a "binding" mode, and then the molecule "flips" to place the macrocycle in a more internal position. Our results show how amphiphilicity and conformation flexibility are critical determinants in the cellular internalization of large molecules.