Rapid method for estimating octanol-water partition coefficient (log Poct) from isocratic RP-HPLC and a hydrogen bond acidity term (A)

The linear solvation equation approach has been used to describe the octanol/water lipophilicity scale (logP(oct)) and the isocratic retention factors (log k) obtained using;reversed phase HPLC with acetonitrile. Both the octanol/water partition coefficients and the RP-HPLC retention data: obtained from the literature, showed good correlation with the molecular descriptors such as size, excess molar refractivity, H-bond acidity/basicity, and polarity/dipolarity. However, the impact of the H-bond acidity term was very different on the two lipophilicity scales. The H-bond acidity term was not significant in describing the octanol/water lipophilicity, while the H-bond acidity of the molecules decreased significantly their RP-HPLC retention. As the other terms had very similar impact on the two lipophilicity scales, it made it possible to convert one scale to the other by incorporating only the H-bond acidity of the compounds as is shown by the equation below, where A is the compound H-bond acidity. log P-oct = 2.067(+/- 0.04) log k(40) + 1.094(+/- 0.08) A + 0.517(+/- 0.05) n = 111 r = 0.982 rms = 0.189 Using the simpler hydrogen bond donor counts (HBC) also helped to align the two lipophilicity scales to each other. log P-oct = 1.913(+/-0.07) log k(40) + 0.367(+/-0.07) HBC + 0.720(+/-0.08) n = 111 r = 0.962 rms = 0.272 The validity of the above equations was tested using a test set of 41 drug compounds with our measured data. The log P-oct values were estimated from isocratic RP-HPLC retention data with the H-bond acidity term and counts, with an error of 0.284 and 0.325 log unit, respectively.