Patterns of non-electrolyte permeability

Reflexion coefficients ($\sigma $'s) for epithelial cells of rabbit gall-bladder for 206 non-electrolytes have been measured and analysed. In general, $\sigma $'s decrease from 1$\cdot $0 to 0 with increasing lipid: water partition coefficients, so that the intermolecular forces governing permeation of most non-electrolytes are the same as those governing partition between a bulk lipid phase and water. The two classes of deviations to this pattern are related to the specific structure of cell membranes. First, highly branched molecules have higher $\sigma $'s (permeate more slowly) than expected from partition coefficients, an effect attributed to anisotropy of membrane lipids. Secondly, the smallest, most lipid-insoluble molecules have lower $\sigma $'s (permeate more readily) than expected, and are also anomalous in that: effects of changes in their structure on $\sigma $ disobey Overton's rules; the inverse relation between $\sigma $ and temperature is less steep for them than for other solutes; and their $\sigma $'s are little affected by decreases in pH which increase $\sigma $'s of other solutes. These anomalies are interpreted to mean that small polar solutes in transit through the membrane interact minimally or not at all with hydrocarbon tails of membrane lipids, but instead follow a route formed by localized concentrations of membrane polar groups associated with 'frozen' water molecules, where the coupling phenomena between permeating water, ions, and small polar-electrolytes observed in cell membranes may also occur.