Toward prediction of alkane/water partition coefficients

摘要

Partition coefficients were measured for 47 compounds in the hexadecane/water (P-hxd) and 1-octanol/water (P-oct) systems. Some types of hydrogen bond acceptor presented by these compounds to the partitioning systems are not well represented in the literature of alkane/water partitioning. The difference, Delta logP, between logP(oct) and logP(hxd) is a measure of the hydrogen bonding potential of a molecule and is identified as a target for predictive modeling. Minimized molecular electrostatic potential (V-min) was shown to be an effective predictor of the contribution of hydrogen bond acceptors to Delta logP. Carbonyl oxygen atoms were found to be stronger hydrogen bond acceptors for their electrostatic potential than heteroaromatic nitrogen or oxygen bound to hypervalent sulfur or nitrogen. Values of V-min calculated for hydrogen-bonded complexes were used to explore polarization effects. Predicted logP(hxd) and Delta logP were shown to be more effective than logP(oct) for modeling brain penetration for a data set of 18 compounds.