David A. Brent

Modeling octanol—water partition coefficients by reversed-phase liquid chromatography

Abstract The dynamic range of a polycratic reversed-phase liquid chromatographic (RPLC) method for measuring hydrophobicity constants (log k ′ w ) for non-ionic, organic molecules was examined. Evidence is presented that indicates that the differential hydrogen bonding effect present in most RPLC methods has been minimized by selection of appropriate stationary and mobile phase conditions. Thus, values of log k ′ w determined for compounds of different net hydrogen bonding properties (non-congeners) can be compared directly. Results indicate that noncongeners congeners with hydrophobicities varying between −0.20 ≤ log k ′ w ≤ 5.27 can be measured by this procedure. Additionally, the net hydrogen bonding property of any solute molecule can be predicted from the chromatographic experiment. Finally, the suppression of hydrogen-bonding discrimination effects in this method is shown to be a result of the low levels of octanol and alkylamine added to the mobile phase.

Measurement of lipophilicity by high performance liquid chromatography comparison with calculated lipophilicity values

Abstract Reversed-phase high-performance liquid chromatography (HPLC) was used to measure the lipophilicities of a series of biphenyl acids and their non-acid precursors. Values obtained by HPLC for the precursors were as predicted from the calculated lipophilicity values. For biphenyl acids, a systematic deviation in the correlation of calculated log P and log k′ was observed (hydrogen-bond acceptors and non-hydrogen-bonding substituents described two separate lines in the correlaton). An explanation of these results is presented, based on steric effects which control the way the biphenhyl acids interact with the stationary phase.