Structural requirements for unsaturated fatty acids and fatty alcohols to induce optimal biological responses: an approach using model membranes.

The permeation induced by unsaturated fatty acids and fatty alcohols through the membrane of dihexadecyl phosphate vesicles was quantified, using [Ru(bpy)3(2+)] ions as a permeant probe. In both the free fatty acid and the free fatty alcohol series, the permeation induced by the unsaturated isomers is higher than that of the corresponding saturated analogues. Moreover the permeant effect associated with free fatty acids or free fatty alcohols is under the control of structural and conformational parameters: carbon chain length, number and position of the double bonds, and the geometry Z or E of the double bond. Optimal membrane perturbing effects are observed for compounds having a carbon chain length ranging from 18 to 20 carbon atoms, incorporating two or four Z double bonds in the center of the carbon chain. Good correlation has been found between the membrane perturbing effect quantified as PD50 values and some of the biological properties associated with these fatty lipids. The PD50 values obtained for free fatty alcohols are in fair agreement with anesthetic properties reported by different authors, (Pringle et al., 1981) while PD50 values obtained for free fatty acids show a good correlation with their activity on the superoxide respiratory burst induced by chemotactic peptides. These preliminary results led to the conclusion that as far as a biological activity directly associated with unsaturated fatty acids or alcohols, involved a membrane barrier passage, the measure of their permeant properties using a DHP vesicle model appears to be an excellent criterion for the quantification of optimal biological effects.