Several chromatographic parameters (RM0 and S obtained from RP-18 TLC with methanol-pH 7.4 phosphate buffer mobile phases by extrapolation to zero concentration of methanol; Rf and RM obtained from RP-18 TLC with acetonitrile-pH 7.4 phosphate buffer 70:30 v/v as a mobile phase) and calculated molecular descriptors (molecular weight-MW; molar volume-VM; polar surface area-PSA; total count of nitrogen and oxygen atoms-(N+O); H-bond donor count-HD; H-bond acceptor count-HA; distribution coefficient-log D; total energy-ET; binding energy-Eb; hydration energy-Eh; energy of the highest occupied molecular orbital-EHOMO; energy of the lowest unoccupied orbital-ELUMO; electronic energy-Ee; surface area-Sa; octanol-water partition coefficient-log P; dipole moment-DM; refractivity-R, polarizability-α) and their combinations (Rf/PSA, RM/MW, RM/VM) were tested in order to generate useful models of solutes' skin permeability coefficient log Kp. It was established that neither RM0 nor S obtained in the conditions used in this study is a good predictor of the skin permeability coefficient. The chromatographic parameters Rf and Rf/PSA were also unsuitable for this purpose. A simple and potentially useful, purely computational model based on (N+O), log D and HD as independent variables and accounting for ca. 83% of total variability was obtained. The evaluation of parameters derived from RM (RM, RM/MW, RM/VM) as independent variables in log Kp models proved that RM/VM is the most suitable descriptor belonging to this group. In a search for a reliable log Kp model based on this descriptor two possibilities were considered: a relatively simple model based on 5 independent variables: (N+O), log D, RM/VM, ET and Eh and a more complex one, involving also Eb, MW and PSA.
Keywords: computational descriptors; skin permeation; thin layer chromatography.