Determination of Octanol/Water Partition Coefficients of Certain Organophosphorus Compounds Using High‐Performance Liquid Chromatography

Abstract

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 PO 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).

Development of novel pesticides based on phytoalexins: Part 2. Quantitative structure–activity relationships of 2‐heteroaryl‐4‐chromanone derivatives

“…For these reasons, the logarithm of the retention factor ( k ) in reversed‐phase HPLC was employed as an alternative hydrophobicity parameter. The relevancy of log k as a hydrophobicity parameter has been shown in the literature 20–25. Retention times ( t R ) were determined on a HP‐1100 HPLC apparatus equipped with an UV absorbance detector (254 nm).…”

“…The relevancy of log k as a hydrophobicity parameter has been shown in the literature. [20][21][22][23][24][25] Retention times (t R ) were determined on a HP-1100 HPLC apparatus equipped with an UV absorbance detector (254 nm). The column was a Description-Eclipse XDB-C 8 (5-mm particle size, 150 mm  4.6 mm), the solvent methanol þ water (60 þ 40 by volume) and the flow rate 1 ml min À1 .…”

Interactions of antisense DNa oliginucletide analogs with phospholid membranes (liposomes)

“…The peak absorbances at 250 nm, for di(deoxyinosine), or at 260 nm, for the longer methylphosphonate oligomers, were corrected for background optical density and used to calculate the partition coefficients. For the phosphorothioates we employed analysis by reversed phase liquid chromatography [36].…”

“…Partition coefficients for oligodeoxynucleoside methylphosphonates from octanol into water at room temperature are shown in Table 3. For comparison, the reported w/o partition coefficient for (dimethyl) methylphosphonate was 4.5 + 1.2 (Mean ± S.D) [36] and that of a 16 mer D-oligo, 5' dCTGACAACATGACTGC 3', has been reported to be 5.7 x 104 [39]. The w/o partition coefficients of the methylphosphonate oligomers were all much greater than that of the model compound (dimethyl) methylphosphonate, implying that deoxynucleoside moieties increase the polarity of the compound.…”

“…We also attempted to determine the w/o partition coefficient of a 14 mer S-oligo antisense to the 5' splice site of 13-globin gene (see Table 1 for sequence).In the case of this phosphorothioate, no detectable partition of the oligomer into octanol could be detected by simple absorbance measurements, so measurements were attempted by liquid chromatography [36]. phonates we used a 15 mer oligonucleotide complementary to peaks were found from octanol fractions.…”