Regression method of the hydrophobicity ruler approach for determining octanol/water partition coefficients of very hydrophobic compounds

A regression method was developed for the hydrophobicity ruler approach, which is an indirect method for determining the octanol/water partition coefficients of very hydrophobic compounds. Two constants introduced into the mathematical model were obtained by regression of the absorption data sampled before the partition equilibrium. A water miscible organic solvent was used to increase the solubility of the very hydrophobic compounds in the aqueous solution so that the hydrophobicity scale was reduced and the equilibration was accelerated. Polydimethylsiloxane/methanol aqueous solution and a series of 21 polychlorinated biphenyls (PCBs) were used to demonstrate the regression method. The PCB compounds with known experimental log Ko/w values served as reference compounds, while the PCB compounds without known log Ko/w values were determined. The distribution coefficients (log Kp/s), uptake and elimination rate constants were obtained from the two regression constants for each compound (reference or unknown). The correlation of the log Kp/s values of the reference PCB compounds with their log Ko/w values was linear (log Ko/w = 2.69 log Kp/s + 0.76, R2 = 0.97). The log Ko/w values were compared with literature values and suggested that some values from the literature far off the calibration line could be inaccurate. The critical experimental factors, the merits of the regression method were discussed.