PARTITIONING OF SUBSTITUTED PHENOLS IN LIPOSOME-WATER, BIOMEMBRANE-WATER, AND OCTANOL-WATER SYSTEMS

The effect of pH, ionic strength, and compound concentration on the li posome-water distribution ratio has been investigated for 20 chloro- a nd nitrophenols covering a wide range of acidities and hydrophobicitie s. A comparison with membrane vesicles from Rhodobacter sphaeroides sh ows that liposomes composed of zwitterionic phosphatidylcholine are ap propriate model systems for mimicking the biomembrane-water partitioni ng behavior of all phenol species, i.e., neutral phenol, charged pheno xide, and ion pair. At high phenoxide concentrations,the simple partit ion model includes an electrostatic term for the buildup of a surface potential on the liposomes due to sorbed phenoxide. The distribution r atios of the neutral phenol species are very similar in the octanol- a nd the liposome-water system, but the charged phenol species partition significantly better into the anisotropic lipid bilayer than into the bulk phase octanol. The liposome-water distribution ratio is a more s uitable descriptor for the uptake of a hydrophobic ionizable compound into biological membranes than the corresponding octanol-water distrib ution ratio. The reported data form an important base for more realist ic predictions of effective phenol concentrations and phenol-to-phenox ide ratios in biological membranes, which is pivotal for assessing the toxicity, in particular, the uncoupling activity of such compounds.