Determination of the Partition Coefficients of Organophosphorus Compounds Using High-Performance Liquid Chromatography.

Octanol/water partition coefficients (log P) for a series of dialkyl alkylphosphonates, dialkyl alkylphosphonothionates, and an alkyl alkylphosphinate have been estimated using reversed-phase high-performance liquid chromatography. The test compounds proved to be readily amenable to the chromatographic procedures employed, although the more lipophilic compounds appeared to be more tolerant to variations in the chromatographic conditions and methods of data handling than were the less lipophilic compounds with regard to the precision and accuracy of the log P values obtained from the retention data. The methodology was validated by carrying out shake-flask experiments with two of the test samples. The rank order of log P values obtained was reasonably predictable, based on the sizes of the alkyl substituents present. The enhancement of lipophilic character attributable to replacement of oxygen by sulfur in the phosphorus oxygen group is also evident from the results. The data for the phosphonates permit the calculation of a value for the hydrophobic fragmental constant for the OPO2 group (f = 2.79).
Prepared in cooperation with Maryland Univ., Baltimore. School of Pharmacy.