Effect of the chirality of the glycerol backbone on the bilayer and nonbilayer phase transitions in the diastereomers of di-dodecyl-beta-D-glucopyranosyl glycerol

Abstract

We have studied the physical properties of aqueous dispersions of 1,2-sn- and 2,3-sn-didodecyl-beta-D-glucopyranosyl glycerols, as well as their diastereomeric mixture, using differential scanning calorimetry and low angle x-ray diffraction. Upon heating, both the chiral lipids and the diastereomeric mixture exhibit characteristically energetic L beta/L alpha phase transitions at 31.7-32.8 degrees C and two or three weakly energetic thermal events between 49 degrees C and 89 degrees C. In the diastereomeric mixture and the 1,2-sn glycerol derivative, these higher temperature endotherms correspond to the formation of, and interconversions between, several nonlamellar structures and have been assigned to L alpha/QIIa, QIIa/QIIb, and QIIb/HII phase transitions, respectively. The cubic phases QIIa and QIIb, whose cell lattice parameters are strongly temperature dependent, can be identified as belonging to space groups Ia3d and Pn3m/Pn3, respectively. In the equivalent 2,3-sn glucolipid, the QIIa phase is not observed and only two transitions are seen at 49 degrees C and 77 degrees C, which are identified as L alpha/QIIb and QIIb/HII phase transitions, respectively. These phase transitions temperatures are some 10 degrees C lower than those of the corresponding phase transitions observed in the diastereomeric mixture and the 1,2-sn glycerol derivative. On cooling, all three lipids exhibit a minor higher temperature exothermic event, which can be assigned to a HII/QIIb phase transition. An exothermic L alpha/L beta phase transition is observed at 30-31 degrees C. A shoulder is sometimes discernible on the high temperature side of the L alpha/L beta event, which may originate from a QIIb/L alpha phase transition prior to the freezing of the hydrocarbon chains. None of the lipids show evidence of a QIIa phase on cooling. No additional exothermic transitions are observed on further cooling to -3 degrees C. However, after nucleation at 0 degrees C followed by a short period of annealing at 22 degrees C, the 1,2-sn glucolipid forms an Lc phase that converts to an L alpha phase at 39.5 degrees C on heating. Neither the diastereomeric mixture nor the 2,3-sn glycerol derivative shows such behavior even after extended periods of annealing. Our results suggest that the differences in the phase behavior of these glycolipid isomers may not be attributable to headgroup size per se, but rather to differences in the stereochemistry of the lipid polar/apolar interfacial region, which consequently effects hydrogen-bonding, hydration, and the hydrophilic/hydrophobic balance.

The interfacial structure of phospholipid bilayers: differential scanning calorimetry and Fourier transform infrared spectroscopic studies of 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine and its dialkyl and acyl-alkyl analogs

“…Other approaches to the study of the effects of lipid interfacial structure on lipid phase behavior have involved comparisons of glycerolipids with ester-linked hydrocarbon chains with appropriate amido-linked counterparts (Curatolo et al, 1982(Curatolo et al, , 1985Chowdhry et al, 1984b), comparisons of normal glycerolipids with analogs containing "conformationally restricted backbones" (Blume and Eibl, 1981;Singer et al, 1983), and comparisons of glycerolipids with 1,3-linked hydrocarbon chains with comparable 1,2-linked analogs (Eibl and Blume, 1979;Serralach et al, 1983;Stumpel et al, 1981;Chowdhry et al, 1984a;Dluhy et al, 1985). It has also been demonstrated that the propensity of some glycerolipids to form inverted nonlamellar phases can be altered by the chirality of the glycerol backbone (Mannock et al, 1992(Mannock et al, , 1994) and by the location of modestly sized hydrophobic groups near the glycerol backbone of the lipid (Lewis et al, 1994a). Such studies clearly show that lipid phase behavior and organization can be significantly altered by chemical changes in this portion of the lipid molecule.…”

Differential scanning calorimetry and X-ray diffraction studies of the thermotropic phase behavior of the diastereomeric di-tetradecyl-beta-D-galactosyl glycerols and their mixture

“…as well as the temperature range over which they are stable, was found to depend on the chirality of the glycerol backbone (Mannock et al, 1992). The absence of stable QlI phases in the lipids studied here2 may be due to a critical difference in the balance of headgroup-hydrocarbon chain contributions to the stability of the fluid phases of the dialkyl 13-GalDAGs with chain lengths of 12 and 14 carbon atoms.…”

“…The f3-Ga1DAGs used in this study were synthesized according to literature methods (Ogawa and Beppu, 1982;van Boeckel et al, 1985;Glew et al, 1991;Mannock et al, 1987Mannock et al, , 1992 using dialkylglycerols prepared from the 1,2-sn or racemic isopropylidene glycerols (Aldrich Chemical Co., Milwaukee, WI) or 2,3-isopropylidene-sn-glycerol (Pfanstiehl Laboratories, Waukegan, IL). The caand (3-anomers of the 1-GalDAGs were separated as their peracetates by chromatography on a silica gel column (Davisil, 200-425 mesh) which was eluted with a gradient of hexane and ethyl acetate.…”

“…DSC measurements were performed with a Perkin Elmer DSC-2C calorimeter equipped with a thermal analysis data station. Lipid samples for DSC were prepared and quantified as reported earlier (Mannock et al, 1992). DSC curves were recorded between -3 and 97°C.…”

DSC Analysis of Surfactant-Based Microstructures

“…These temperatures correspond to the two eutectic mixtures of enantiomeric and racemic crystals, and the shape of the (pseudo) binary phase diagram indicates that the crystal of the racemate is a racemic compound, as in the case of the bulk compound. Chiral discrimination has been found in a number of DSC studies of phospholipid bilayers [120][121][122][123][124][125][126]. 14) when equimolar solutions of the R and S isomers were mixed.…”