Estimating n-octanol-water partition coefficients for neutral highly hydrophobic chemicals using measured n-butanol-water partition coefficients

Abstract

Direct measurement of the n-octanol partition coefficients (KOW) for highly hydrophobic organic chemicals is extremely difficult because of the extremely low concentrations present in the water phase. n-Butanol/water partition coefficients (KBW) are generally much lower than KOW due to the increased solubility of solute in the alcohol saturated aqueous phase, and therefore become easier to measure. We measured the KBW for 25 neutral organic chemicals having measured log KOWs ranging from 2 to 9 and 4 additional highly hydrophobic chemicals, with unmeasured KOWs, having estimated log KOWs ranging from 6 to 18. The measured log KBW and log KOW values were linearly related, r2 = 0.978, and using the regression developed from the data, KOWs were predicted for the 4 highly hydrophobic chemicals with unmeasured KOWs. The resulting predictions were orders of magnitude lower than those predicted by a variety of computational models and suggests the estimates of KOW in the literature for highly hydrophobic chemicals (i.e., log KOW greater than 10) are likely incorrect by several orders of magnitude.