Evaluation of liposome-water partitioning of organic acids and bases. 1. Development of a sorption model

Liposome-water systems are used increasingly in lieu of the octanol-water s ystem to evaluate and describe the partitioning of organic compounds betwee n biological systems and water. In particular, for hydrophobic ionogenic co mpounds (HIOCs), the liposome-water (and biological membrane-water) distrib ution ratios of the ionic species are generally much greater than the corre sponding octanol-water distribution ratios, even at high electrolyte concen trations where ion pair formation increases the apparent distribution of th e ionized species into octanol. In this paper,we describe a comprehensive m odel that allows one to describe the complete data set of experimental lipo some-water distribution ratios D-lipw measured by equilibrium dialysis as a function of concentration, pH, and ionic strength. Test compounds included acids (chloro- and (alkyl-)nitrophenols) and bases (methylated amines) cov ering a wide range of hydrophobicity and acidity and including several comp ounds of environmental concern. The partitioning model features an electros tatic term to account for the build-up of a surface potential when charged species are sorbed to the lipid bilayer at the lipid-water interface. tonic strength dependence was fully accounted for by the interfacial electrostat ics and the activity coefficients of the charged molecules in the aqueous p hase. Activity coefficients were set to unity for neutral species and for a ll species in the membrane. No ion pair formation needed to be postulated t o explain the experimental data in the proposed model. In addition liposome -water partition coefficients for the neutral and corresponding charged spe cies of HIOCs can be deduced directly from the model parameters.