| Abstract
| - The effect of pH, ionic strength, and compoundconcentration on the liposome−water distribution ratiohas been investigated for 20 chloro- and nitrophenolscovering a wide range of acidities andhydrophobicities. A comparison with membranevesicles from Rhodobacter sphaeroides showsthatliposomes composed of zwitterionic phosphatidylcholine are appropriate model systems for mimickingthe biomembrane−water partitioning behavior ofall phenol species, i.e., neutral phenol, charged phenoxide, and ion pair. At high phenoxide concentrations, the simple partition model includes an electrostaticterm for the buildup of a surface potential on theliposomes due to sorbed phenoxide. The distributionratios of the neutral phenol species are very similarin the octanol− and the liposome−water system, butthe charged phenol species partition significantlybetter into the anisotropic lipid bilayer than into thebulk phase octanol. The liposome−water distribution ratio is a more suitable descriptor for the uptakeof a hydrophobic ionizable compound into biologicalmembranes than the corresponding octanol−waterdistribution ratio. The reported data form animportant base for more realistic predictions of effectivephenol concentrations and phenol-to-phenoxide ratiosin biological membranes, which is pivotal forassessing the toxicity, in particular, the uncouplingactivity of such compounds.
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