Prediction of flux through polydimethylsiloxane membranes using atomic charge calculations: Application to an extended data set

The maximum steady state flux of 171 compounds through PDMS membranes was predicted using a refinement of a previously developed empirical quantitative structure-transportability relationship (QSTR) produced using the reported flux data for 103 compounds. The model utilized partial atomic charge, solubility, and molecular weight as predictors. The predicted data set includes a variety of substituted benzenes, naphthalenes, thiophenes, benzimidazoles, pyridines, quinolines, isoquinolines, pyrimidines, triazoles and lesser numbers of other heterocyclic classes of compounds over a wide range of polarity. Maximum steady state flux was measured using isopropyl alcohol as solvent. Molecular models of all the compounds were simulated using SYBYL 6.0 molecular modeling software. The atomic charge of each individual compound was computed with the Gast-Huck method using the same software. Results show that the simple QSTR equation is capable of accurately predicting the steady state flux of a variety of compounds. Contribution of atomic charge to mass transport phenomena was further verified by the prediction of the apparent permeability calculated from the steady state flux data. Permeability decreases significantly as the atomic charge of diffusant is increased. Predicted results show that atomic charges can be used to represent the polarity and be correlated to the polarity-related properties of an electrically neutral compound.