Binding of small alcohols to a lipid bilayer membrane: does the partitioning coefficient express the net affinity?

The total vapor pressures at 26 degreesC of binary (water-alcohol) and tern ary (water-alcohol-vesicle) systems were measured for sis short chain alcoh ols. The vesicles were unilamellar dipalmitoyl phosphatidylcholine (DMPC). The data was used to evaluate the effect of vesicles on the chemical potent ial of alcohols expressed as the preferential binding parameter of the alco hol-lipid interaction, Gamma (23). This quantity is a thermodynamic (model- free) measure of the net strength of membrane-alcohol interactions. For the smaller investigated alcohols (methanol, ethanol and 1-propanol) Gamma (23 ) was negative. This is indicative of so-called preferential hydration, a c ondition where the affinity of the membrane for water is higher than the af finity for the alcohol. For the longer alcohols (1-butanol, 1-pentanol, 1-h exanol) Gamma (23) was positive and increasing with increasing chain length . This demonstrates preferential binding, i.e. enrichment of alcohol in the membrane and a concomitant depletion of the solute in the aqueous bulk. Th e measured values of Gamma (23) were compared to the number of alcohol-memb rane contacts specified by partitioning coefficients from the literature. I t was found that for the small alcohols the number of alcohol-membrane cont acts is much larger than the number of preferentially bound solutes. This d iscrepancy, which is theoretically expected in cases of very weak binding, becomes less pronounced with increasing alcohol chain length, and when the partitioning coefficient exceeds approximately 3 on the molal scale (10(2) in mole fraction units) it vanishes. Based on this, relationships between s tructural and thermodynamic interpretations of membrana partitioning are di scussed. (C) 2001 Elsevier Science B.V. All rights reserved.