Passive permeability of dihexadecylphosphate vesicles altered by aliphatic alcohols and omega-diols

Alcohols act as anaesthetics only up to a certain chain length, beyond which their biological activity disappears. Although the molecular nature of general target sites remains unknown, presently available data support the hypothesis that this 'cut-off' in anaesthetic activity could be due to a corresponding cut-off in the absorption of long-chain alcohols into lipid-bilayer portions of nerve membranes. To test this hypothesis, we developed a method based on leakage of Ru(bpy)3(2+) ions across the membrane of dihexadecylphosphate (DHP) vesicles induced by aliphatic alcohols (C1 to C18) and some of their omega-diol. The permeant effects of aliphatic linear alcohols expressed as PD50 values rise to a maximum for n-dodecanol (PD50 = 2 x 10(-3) M 1(-1]. Dodecanol was found to be the alcohol which presents the greatest anaesthetic potency among the series of linear aliphatic alcohols (cut-off anaesthetic effect). The results are discussed in terms of the structural physicochemical and geometrical characteristics of the permeating alcohols.