Estimation of molecular linear free energy relationship descriptors. 4. Correlation and prediction of cell permeation

Purpose. The passage of molecules across cell membranes is a crucial step i n many physiological processes. We therefore seek physical models of this p rocess, in order to predict permeation for new molecules, and to better und erstand the important interactions which determine the rate of permeation. Methods. Several sets of cell permeation data reported by Collander have be en correlated against calculated Linear Free Energy Relation (LFER) descrip tors. These descriptors, taken as the sum of fragmental contributions, cove r the size, polarity, polarizability, and hydrogen bonding capacity of each molecule. Results. For 36 values of permeation into Chara ceratophylla cells, a model (sd = 0.24) dominated by hydrogen bond acidity is found, while for 63 rate s of permeation values into Nitella cells a very similar model yields sd = 0.46. Comparisons between the two cell types are made directly for 17 compo unds in both data sets, indicate differences of a similar magnitude to the standard deviations of the above models. The two data sets can be combined to yield a generic model of rates of permeation into cells, resulting in an sd value of 0.46 for a total of 100 data points. Conclusions. Models allowing accurate prediction of cell permeation have be en constructed using 100 experimental data. We demonstrate that hydrogen bo nd acidity is the dominating factor in determining cell permeation for two distinct species of algal cell.