Structure and interactive properties of highly fluorinated phospholipid bilayers

Abstract

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.

Synthesis and monolayer properties of double-chained phosphatidylcholines containing perfluoroalkyl groups of different length

“…The proposed PCs formed stable liquid-condensed monolayers at the air-water interface with higher collapse pressures than dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) [13][14][15]. The proposed fluorinated PCs, however, formed crystalline or gel phase bilayers at ambient temperatures [16], which is not preferable for biotechnological uses. In general, the molecules containing long perfluoroalkyl moiety tend to form rigid self-assemblies in water.…”

“…[2,3,[6][7][8][9][10]. Many studies on syntheses and interfacial chemical characterization of fluorinated phosphatidylcholines (PCs) as fluorinated amphiphiles have been carried out so far [4,[11][12][13][14][15][16][17][18]. Vierling and co-workers reported the syntheses of fluorinated PCs containing C 17 or C 19 carbon chains [13][14][15].…”

Enhancedin vitro andin vivo cationic lipid-mediated gene delivery with a fluorinated glycerophosphoethanolamine helper lipid

“…[F8E11][C16]OPE or F ‐PE (Figure 1), on in vitro and in vivo cationic lipid‐mediated gene transfer. Such molecules display a more pronounced cone‐shape geometry than DOPE owing to the larger size of highly fluorinated chains as compared with hydrocarbon ones (cross sectional area of about 30 Å 2 for a fully extended chain of nCF 2 groups vs about 20 Å 2 for a nCH 2 chain)10. Such fluorinated glycerophosphoethanolamines should therefore display a greater tendency to promote a transition from the lamellar phase into the inverted hexagonal HII phase and, consequently, a greater effectiveness in disrupting membranes than DOPE.…”

Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase

“…When the fluorine substitution is not located on the terminal carbon, DSC data reveal that the physical properties are only modestly changed and they are largely miscible with the non-fluorinated parent lipid [70]. Lipids with more fluorine, such as when the 13-16 carbons are perfluorinated, do not spontaneously interdigitate either [71,72]. Therefore, it is the interaction of the polar terminal C-F bond with the aqueous interface that encourages interdigitation [67].…”