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

Abstract

Chromatographic retention factors (log k_KERATIN) 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 K_p) in vitro. However, log k_KERATIN is not a sufficiently good predictor of skin permeability coefficient to be used as a sole descriptor in log K_p 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 k_IAM) and the results of log K_p predictions using multiple linear regression (MLR) models are moderately satisfying. In this study, the values of log k_KERATIN obtained by Turowski and Kaliszan were correlated with a set of descriptors calculated using SwissADME software. It was discovered that log k_KERATIN 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 k_KERATIN 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 k_KERATIN could be used as a descriptor in MLR models of log k_pin combination with other parameters, such as PSA or H-bond descriptors.