STRUCTURE AND INTERACTIONS OF ETHER-LINKED AND ESTER-LINKED PHOSPHATIDYLETHANOLAMINES

The ether-linked phospholipid 1,2-dihexadecylphosphatidylethanolamine (DHPE) was studied as a function of hydration and in fully hydrated mixed phospholipid systems with its ester-linked analogue 1,2-dipalmitoylphosphatidylethanolamine (DPPE). A combination of differential scanning calorimetry (DSC) and X-ray diffraction was used to examine the phase behavior of these lipids. By DSC, from 0 to 10 wt % H2O, DHPE displayed a single reversible transition that decreased from 95.2 to 78.8-degrees-C and which was shown by X-ray diffraction data to be a direct bilayer gel to inverted hexagonal conversion, L-beta --> H(II). Above 15% H2O, two reversible transitions were observed which stabilized at 67.1 and 92.3-degrees-C above 19% H2O. X-ray diffraction data of fully hydrated DHPE confirmed the lower temperature transition to be a bilayer gel to bilayer liquid-crystalline (L-beta --> L-alpha) phase transition and the higher temperature transition to be a bilayer liquid-crystalline to inverted hexagonal (L-alpha --> H(II)) phase transition. The lamellar repeat distance of gel-state DHPE increased as a function of hydration to a limiting value of 62.5 angstrom at 19% H2O (8.6 mol of water/mol of DHPE), which corresponds to the hydration at which the transition temperatures are seen to stabilize by DSC. Electron density profiles of DHPE, in addition to calculations of the lipid layer thickness, confirmed that DHPE in the gel state forms a noninterdigitated bilayer at all hydrations. Fully hydrated mixed phospholipid systems of DHPE and DPPE exhibited two reversible transitions by DSC. X-ray diffraction data of a mixture containing 10 mol % DPPE identified the lower temperature transition as an L-beta --> L-alpha phase transition and the higher temperature transition as an L-alpha --> H(II) phase transition. Addition of DHPE to DPPE slightly increased the L-beta --> L-alpha transition temperature in a linear fashion, suggesting complete miscibility of the L-beta and L-alpha phases. Increasing amounts of DHPE in DPPE decreased by a greater amount the temperature of the L-alpha --> H(II), transition from the extrapolated value in DPPE. The presence of the ether linkage apparently stabilized the L-beta and H(II) phases and destabilized the L-alpha phase in the mixed DHPE/DPPE system.