McIntosh T J, Simon S A, Vierling P, Santaella C, Ravily V
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Biophys J. 1996 Oct;71(4):1853-68. doi: 10.1016/S0006-3495(96)79385-2.
Because liposomes containing fluoroalkylated phospholipids are being developed for in vivo drug delivery, the structure and interactive properties of several fluoroalkylated glycerophosphocholines (PCs) were investigated by x-ray diffraction/osmotic stress, dipole potential, and hydrophobic ion binding measurements. The lipids included PCs with highly fluorinated tails on both alkyl chains and PCs with one hydrocarbon chain and one fluoroalkylated chain. Electron density profiles showed high electron density peaks in the center of the bilayer corresponding to the fluorine atoms. The height and width of these high density peaks varied systematically, depending on the number of fluorines and their position on the alkyl chains, and on whether the bilayer was in the gel or liquid crystalline phase. Wide-angle diffraction showed that in both gel and liquid crystalline bilayers the distance between adjacent alkyl chains was greater in fluoroalkylated PCs than in analogous hydrocarbon PCs. For interbilayer separations of less than about 8 A, pressure-distance relations for fluoroalkylated PCs were similar to those previously obtained from PC bilayers with hydrocarbon chains. However, for bilayer separations greater than 8A, the total repulsive pressure depended on whether the fluoroalkylated PC was in a gel or liquid-crystalline phase. We argue that these pressure-distance relations contain contributions from both hydration and entropic repulsive pressures. Dipole potentials ranged from -680 mV for PCs with both chains fluoroalkylated to -180 mV for PCs with one chain fluoroalkylated, compared to +415 mV for egg PC. The change in dipole potential as a function of subphase concentration of tetraphenyl-boron was much larger for egg PC than for fluorinated PC monolayers, indicating that the fluorine atoms modified the binding of this hydrophobic anion. Thus, compared to conventional liposomes, liposomes made from fluoroalkylated PCs have different binding properties, which may be relevant to their use as drug carriers.
由于含氟烷基化磷脂的脂质体正被开发用于体内药物递送，通过X射线衍射/渗透压、偶极电势和疏水离子结合测量研究了几种氟烷基化甘油磷酸胆碱（PCs）的结构和相互作用特性。这些脂质包括两条烷基链上都有高度氟化尾部的PCs以及一条烃链和一条氟烷基化链的PCs。电子密度分布图显示双层中心对应氟原子处有高电子密度峰。这些高密度峰的高度和宽度根据氟原子数量、它们在烷基链上的位置以及双层处于凝胶相还是液晶相而系统地变化。广角衍射表明，在凝胶和液晶双层中，氟烷基化PCs中相邻烷基链之间的距离比类似的烃基PCs中的距离更大。对于小于约8埃的双层间距，氟烷基化PCs的压力-距离关系与先前从具有烃链的PC双层获得的关系相似。然而，对于大于8埃的双层间距，总排斥压力取决于氟烷基化PC是处于凝胶相还是液晶相。我们认为这些压力-距离关系包含水合和熵排斥压力的贡献。偶极电势范围从两条链都被氟烷基化的PCs的-680毫伏到一条链被氟烷基化的PCs的-180毫伏，相比之下，鸡蛋PC的为+415毫伏。对于鸡蛋PC，偶极电势随四苯基硼亚相浓度的变化比氟化PC单层的变化大得多，表明氟原子改变了这种疏水阴离子的结合。因此，与传统脂质体相比，由氟烷基化PCs制成的脂质体具有不同的结合特性，这可能与其作为药物载体的用途相关。
