Determination of the hydrophobicity of organic compounds measured as log Po/w through a new chromatographic method

A new chromatographic method to determine the octanol–water partition coefficient (log Po/w) of organic substances is proposed in this paper. This method is based on a previously reported model that relates the retention factor in reversed-phase liquid chromatography with solute (p  ), mobile phase (PmN) and stationary phase (PsN) polarity parameters: log⁡k=(log⁡k)0+p(PmN−PsN). PmN values are calculated through expressions that depend only on the organic solvent fraction in the mobile phase. (log k)0 and PsN parameters are characteristic of the chromatographic system and are determined from the retention of a selected set of 12 compounds. Then, the p value of a solute determined in a properly characterized system is easily derived from the retention factor data. Solute p values are slightly dependent on the chromatographic system but they are linearly related to those obtained in the reference system (Spherisorb ODS-2 column and acetonitrile as organic modifier). Therefore, they can be easily transferred from any experimental system to the reference one. A Quantitative Structure–Property Relationship study reveals that the p parameter in the reference chromatographic system depends, mainly, on the hydrophobicity of the compound, expressed as the n-octanol/water partition coefficient (log Po/w), and five additional structural descriptors which can be easily calculated through the CODESSA program from the chemical structure of the solute. In this work the p descriptors of a wide set of structurally different organic compounds have been determined in several chromatographic systems and transferred to the reference one from these and the CODESSA structural parameters. The log Po/w values have been determined. The obtained values agree with those determined from classical experimental techniques and validate the new method as a useful tool to determine the hydrophobicity of a wide variety of compounds in a broad log Po/w range.