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 ternary (water-alcohol-vesicle) systems were measured for six short chain alcohols. The vesicles were unilamellar dipalmitoyl phosphatidylcholine (DMPC). The data was used to evaluate the effect of vesicles on the chemical potential of alcohols expressed as the preferential binding parameter of the alcohol-lipid interaction, gamma23. 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) gamma23 was negative. This is indicative of so-called preferential hydration, a condition where the affinity of the membrane for water is higher than the affinity for the alcohol. For the longer alcohols (1-butanol, 1-pentanol, 1-hexanol) gamma23 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. The measured values of gamma23 were compared to the number of alcohol-membrane contacts specified by partitioning coefficients from the literature. It was found that for the small alcohols the number of alcohol-membrane contacts is much larger than the number of preferentially bound solutes. This discrepancy, 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 structural and thermodynamic interpretations of membrane partitioning are discussed.