Passive Permeability of Planar Lipid Bilayers to Organic Anions.

The membrane permeability P of organic ions was reported to be governed by the structure of the permeating molecule. Thus far, it is unclear whether the ion structure alters membrane partition or translocation proper across the membrane. Here, we obtained P values for 24 anionic compounds (18 concrete values, 6 upper limits) measuring the current that they carry through folded planar lipid bilayers. The P values range over more than 10 log units. Our measured permeability values correlate well (r = 0.95; logRMSE 0.74) with the hexadecane/water partition coefficients of the respective chemicals predicted by the COSMO-RS theory. Other attempts to predict P from the partition coefficient of the neutral molecule and from the solvation energy (Born energy) that opposes transfer into the membrane once the molecule is charged were unsuccessful. The uncertainties in assigning an effective radius to nonspherical molecules were much too large. The observation underlines that the actual structure of the molecules needs to be considered to predict partition and thus P by the solubility-diffusion model.