Estimation of Molecular Linear Free Energy Relationship Descriptors. 4. Correlation and Prediction of Cell Permeation

AbstractPurpose. The passage of molecules across cell membranes is acrucial step in many physiological processes. We therefore seek physicalmodels of this process, in order to predict permeation for new molecules,and to better understand the important interactions which determinethe rate of permeation. Methods. Several sets of cell permeation data reported byCollander have been correlated against calculated Linear Free Energy Relation(LFER) descriptors. These descriptors, taken as the sum of fragmentalcontributions, cover the size, polarity, polarizabilty, and hydrogenbonding capacity of each molecule. Results. For 36 values permeation into Chara ceratophyllacells, a model (sd = 0.24) dominated by hydrogen bond acidity is found, whilefor 63 rates of permeation values into Nitella cells a very similar modelyields sd = 0.46. Comparisons between the two cell types are madedirectly for 17 compounds in both data sets, indicate differences of asimilar magnitude to the standard deviations of the above models. Thetwo data sets can be combined to yield a generic model of rates ofpermeation into cells, resulting in an sd value of 0.46 for a total of100 data points. Conclusions. Models allowing accurate prediction of cell permeationhave been constructed using 100 experimental data. We demonstratethat hydrogen bond acidity is the dominating factor in determining cellpermeation for two distinct species of algal cell.