Interaction of small molecules with phospholipid bilayer membranes: A spin label study

Multilamellar spin labelled liposomes were prepared from dipalmitoyl or dimyristoyl phosphatidylcholine, dicetyl phosphate, and the spin probe 12-doxyl stearate methyl ester. The effects of a series of benzene and adamantane derivatives, on fatty acyl chain motion was measured through changes in the electron spin resonance spectra of these liposomes. All the compounds tested, increased lipid chain motion to a variable degree. In general, molecules possessing a polar group were more potent than those lacking such a group and lipophilicity per se correlated poorly with the relative order of these compounds. Within the adamantane series separating the polar group from the cage structure by the insertion of methylene groups further enhanced the capacity of the molecule to increase hydrocarbon chain mobility. These observations are consistent with the hypothesis that the location of the additive within the bilayer is the main determinant of its effectiveness in increasing fatty acyl chain motion.