The Permeation of Neutral Molecules, Ions, and Ionic Species Through Membranes: Brain Permeation as an Example

Known descriptors for ions and ionic species (deprotonated carboxylic acid anions and protonated base cations) can be combined with descriptors for neutral species to obtain a general equation for permeation from saline through the blood-brain barrier. The equation can be used to indicate the compound factors that influence permeation and to show how substituent effects on compounds may be altered to increase or decrease the rate of permeation. It is shown that log PS values for carboxylate anions are about 2.0 log units less than those for the neutral carboxylic acids, and that log PS values for protonated base cations are about 1.0 log units less than those for the neutral bases. It is possible to use the obtained general equation to calculate log PS for an acid or a base that is either totally ionized or partly ionized in the saline perfusate. The same method can be used to analyze water-artificial membrane partition coefficients of a set of compounds that include ionized species.