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 system to evaluate and describe the partitioning of organic compounds between biological systems and water. In particular, for hydrophobic ionogenic compounds (HIOCs), the liposome-water (and biological membrane-water) distribution ratios of the ionic species are generally much greater than the corresponding octanol-water distribution ratios, even at high electrolyte concentrations where ion pair formation increases the apparent distribution of the ionized species into octanol. In this paper,we describe a comprehensive model that allows one to describe the complete data set of experimental liposome-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) covering a wide range of hydrophobicity and acidity and including several compounds of environmental concern. The partitioning model features an electrostatic 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 electrostatics and the activity coefficients of the charged molecules in the aqueous phase. Activity coefficients were set to unity for neutral species and for all species in the membrane. No ion pair formation needed to be postulated to explain the experimental data in the proposed model. In addition liposome-water partition coefficients for the neutral and corresponding charged species of HIOCs can be deduced directly from the model parameters.