Chromatographic Retention Factor Obtained on Immobilized Keratin Stationary Phase—What Molecular Properties Does It Encode?

Abstract

Chromatographic retention factors (log kKERATIN) of 33 molecules were obtained on an immobilized keratin stationary phase by Turowski and Kaliszan (J. Pharm. Biomed. Anal. 15, 1997, 1325–1333). Their objective was to develop a novel stationary phase that could be used to investigate the skin permeability coefficient of solutes (log Kp) in vitro. However, log kKERATIN is not a sufficiently good predictor of skin permeability coefficient to be used as a sole descriptor in log Kp models. Turowski and Kaliszan reported that this descriptor can be used in combination with the chromatographic retention factor obtained by Immobilized Artificial Membrane Chromatography (log kIAM) and the results of log Kp predictions using multiple linear regression (MLR) models are moderately satisfying. In this study, the values of log kKERATIN obtained by Turowski and Kaliszan were correlated with a set of descriptors calculated using SwissADME software. It was discovered that log kKERATIN encodes primarily lipophilicity, solubility, and molecular size descriptors, which are important factors governing the ability of compounds to cross the skin barrier. On the other hand, log kKERATIN does not correlate with polar surface area (PSA) and the molecule’s ability to form hydrogen bonds—which are important properties in the context of solutes’ skin permeability. It was concluded that log kKERATIN could be used as a descriptor in MLR models of log kpin combination with other parameters, such as PSA or H-bond descriptors.

Keywords

• immobilized keratin stationary phase
• HPLC
• QSAR models
• skin permeability coefficient
• calculated descriptors