Physico-chemical interpretation and prediction of the dimyristoyl phosphatidyl choline-water partition coefficient

The dimyristoyl phosphatidyl choline (DMPC)-water partition coefficient (log KDMPC-W) has been proposed as an alternative to the 1-octanol-water system (log K-OW) for describing molecular hydrophobicity. In this study literature values of log KDMPC-W for 49 compounds were collated. Quantitative structure-activity relationships (QSARs) were developed for log KDMPC-W in an attempt to develop a predictive model for its estimation and to investigate its meaning. Despite the considerable differences in molecular structure between DMPC and 1-octanol, log KDMPC-W and log K-OW were found to be very strongly related, suggesting there is little advantage in the use of DMPC over 1-octanol as the non-polar phase in partitioning studies. Aliphatic amines were found to have a greater affinity for DMPC than octanol, a phenomenon that may be explained by their protonated nature. Highly hydrophobic compounds were also poorly discriminated by the DMPC system. Other QSARs for the prediction of log KDMPC-W, not including log K-OW, confirmed the role of molecular branching, size and carbon content on the partition coefficient. (C) 2002 Elsevier Science B.V. All rights reserved.