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

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