Determination of the Partition and Distribution Coefficients of Biologically Active Compounds by Reversed-Phase Thin-Layer Chromatography

The relative lipophilicity of bioactive derivatives of 2-[1-(4-alkyl-piperazinyl)]benzothiazoles, 2-[4-(1-alkyl)piperidinyl]benzothiazo-les, 2-(N,N’-dimethyl-1,2-ethanediamino)benzothiazoles, and 2-1-(4-aminopiperidinyl)benzothiazoles has been determined by rever-sed-phase thin-layer chromatography. RM values of these compounds were determined with acetone-buffer mobile phases and extrapolated to 100% aqueous conditions. The lipophilicity was also determined by using optimized structures of the investigated compounds based on quantum mechanical calculations of the chemical structures (HyperChem 7.0). The distribution coefficients of the examined compounds were determined by use of the calculated ‘correction for dissociation’ descriptor. A correction was made based on the dissociation constants of the compounds, which were determined spectrophotometrically. We present a method for calculation of partition coefficients for ionizable compounds at a given pH. This property can be useful in analysis of quantitative structure-activity relationships. The distribution coefficients and the actual partition coefficient (at pH 7.4) were calculated for benzoth-iazole derivatives and for other drugs with different structures. The validity of calculations was checked by comparison with available experimental partition and distribution coefficients.