Comparative Dynamic Stabilities of Cyclopropyl and Olefinic Model Lipids in Liposomes. A Coordinated Kinetic and Spectroscopic Study

Cyclopropanated dihydrosterculoyl (3-F, 3-NF) and unsaturated oleoyl (cis-2-F, cis-2-NF) ammonium ion lipids were prepared. Liposomes were created by sonication of 1:10 functional/nonfunctional lipid blends. The small (300–450 A) liquid crystalline (T_c 15 °C) liposomes were surface differentiated by exovesicular glutathione in an endovesicvdar/exovesicular pH gradient of 3.9/8. At 25 °C, the cyclopropyl liposomes of 3 reequilibrated by transbilayer lipid migration much more slowly (ti_1/2=16 min) than the oleoyl liposomes of 2 (t_1/2 <1 min). The origins of this difference were traced to variations in the lipids' acyl chain conformational states. Fourier transform IR studies revealed that the acyl chains of 3 contained fewer highly disruptive double gauche conformational sites than the chains of 2. This can be associated with better chain packing, increased chain order, and the observed enhanced resistance to lipid “flip-flop” in liposomes of 3.