DYNAMICS OF A BOLAAMPHIPHILIC LIPID IN A BILAYER LIPOSOME

The ''hemimacrocyclic'', bolaamphiphilic, functional ammonium ion lipid, 1,1'-dotriacontamethylenoxybis(2-hexadecyloxypropane-3-Q), where Q is -N,N-dimethyl-N-[4-nitro-1-(benzoyloxy)-3-benzyl]ammonium bromide, 5-F, was synthesized. Liposomes of 5-F and the (nonfunctional) monopolar lipid, 1,2-dihexadecyloxy-3-propane-N,N,N-trimethylammonium bromide, 4-NF (1:14), were created by sonication. These small (d approximately 300 angstrom), gel phase (T(c) = 39-degrees-C) liposomes were surface differentiated by exovesicular glutathione at an exovesicular/endovesicular pH gradient of 8/4. The differentiation kinetics indicated that approximately 70% of the functional groups of 5-F had been in exovesicular locations, whereas approximately 30% occupied endovesicular sites. Endovesicular/exovesicular flip-flop reequilibration of the differentiated 5-F/4-NF liposomes occurred with t1/2 approximately 5 min at 40-degrees-C, similar to the behavior of conventional 4-F/4-NF bilayer liposomes. (4-F is 1,2-dihexadecyloxypropane-3-Q.) The results suggest that at least 40% of the 5-F lipid molecules adopt U-plan conformations in the 4-NF liposomes; uniformly extended, bilayer-bridging conformations for the 5-F bolaamphiphiles are excluded.