Because liposomes containing fluoroalkylated phospholipids are being d
eveloped for in vivo drug delivery, the structure and interactive prop
erties of several fluoroalkylated glycerophosphocholines (PCs) were in
vestigated by x-ray diffraction/osmotic stress, dipole potential, and
hydrophobic ion binding measurements. The lipids included PCs with hig
hly fluorinated tails on both alkyl chains and PCs with one hydrocarbo
n chain and one fluoroalkylated chain. Electron density profiles showe
d high electron density peaks in the center of the bilayer correspondi
ng to the fluorine atoms. The height and width of these high density p
eaks varied systematically, depending on the number of fluorines and t
heir position on the alkyl chains, and on whether the bilayer was in t
he gel or liquid crystalline phase. Wide-angle diffraction showed that
in both gel and liquid crystalline bilayers the distance between adja
cent alkyl chains was greater in fluoroalkylated PCs than in analogous
hydrocarbon PCs, For interbilayer separations of less than about 8 An
gstrom, pressure-distance relations for fluoroalkylated PCs were simil
ar to those previously obtained from PC bilayers with hydrocarbon chai
ns. However, for bilayer separations greater than 8 Angstrom, the tota
l repulsive pressure depended on whether the fluoroalkylated PC was in
a gel or liquid-crystalline phase, We argue that these pressure-dista
nce relations contain contributions from both hydration and entropic r
epulsive pressures. Dipole potentials ranged from -680 mV for PCs with
both chains fluoroalkylated to -180 mV for PCs with one chain fluoroa
lkylated, compared to +415 mV for egg PC. The change in dipole potenti
al as a function of subphase concentration of tetraphenylboron was muc
h larger for egg PC than for fluorinated PC monolayers, indicating tha
t the fluorine atoms modified the binding of this hydrophobic anion, T
hus, compared to conventional liposomes, liposomes made from fluoroalk
ylated PCs have different binding properties, which may be relevant to
their use as drug carriers.