Permeability through DOPC/dodecane membranes: measurement and LFER modelling

The permeabilities of 43 ionisable compounds through membranes consisting of 2% dioleylphosphatidylcholine (DOPC) in dodecane at pH values between 3 and 10 have been measured. The observed values are corrected for the effects of ionisation and diffusion through the unstirred water layer in order to obtain estimates of intrinsic permeability. The intrinsic permeabilities are modelled using Abraham's linear free energy relation method. This not only provides a predictive model of membrane permeability, but also reveals the factors determining passive permeation through membranes made from 2% DOPC in dodecane. Hydrogen bonding dominates, acting to strongly inhibit permeation, polarity/polarisability effects are less important, and size acts to enhance permeation.