Abstract
Comparative molecular field analysis (CoMFA) combined with various physicochemical parameters were used to develop three-dimensional quantitative structure–transportability relationships (3-D QSTR) to predict membrane flux for 108 aromatic and heteroaromatic compounds through polydimethylsiloxane (PDMS) membranes in isopropyl alcohol (IPA). Sybyl, a comprehensive computational molecular modeling package, was used to analyze the data. Optimized molecular models were selected using molecular modeling techniques. Partial least-squares (PLS) regression combined with crossvalidation or bootstrapping was used as the statistical method to establish the predictive models. Prediction was good for the steady-state flux using both steric and electrostatic field descriptors combined with a functional group classification technique. Predictive ability was substantially increased in a model using CoMFA descriptors along with log mole fraction solubility for the penetrants in isopropanol, a hydrophobic term, f chex, which is used to estimate the partition coefficient between cyclohexane and water, and the addition of an intramolecular hydrogen bonding (IHB) term. The crossvalidated r 2 and the conventional r 2 for this model were 0.951 and 0.973, respectively. Excellent predictions are demonstrated for the membrane flux of the compounds both inside and outside the data domain.
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Liu, R., Matheson, L.E. Comparative Molecular Field Analysis Combined with Physicochemical Parameters for Prediction of Polydimethylsiloxane Membrane Flux in Isopropanol. Pharm Res 11, 257–266 (1994). https://doi.org/10.1023/A:1018959525339
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DOI: https://doi.org/10.1023/A:1018959525339