Passive transport across bilayer lipid membranes: Overton continues to rule

Abstract
According to Overton's rule, membrane permeability (PM) of a molecule increases with its hydrophobicity. Experiments with a series of carboxylic acids now suggest the opposite: the most hydrophilic acid exhibited the highest PM (1). The experiments, however, do not justify this conclusion for the following reasons: (i) The reported membrane resistance (RM = 1/PM = 1/2.2 × 10−3 cm/s) is much lower than that of near-membrane unstirred layers (UL) (RUL = 1/PUL). As every resistance adds to the total resistance (R = 1/P) (2), we arrive at where D, δ1, and δ2 denote the diffusion coefficient and the thicknesses of the first and …