Phospholipids chiral at phosphorus. 12. Configurational effect on the thermotropic properties of chiral dipalmitoylthiophosphatidylcholine

Abstract

Differential scanning calorimetry (DSC) studies of the diastereomers of 1,2-dipalmitoyl-sn-glycer0-3-thiophosphocholine (DPPsC) have been carried out to determine the effect of phosphate structure and configuration on the phase-transition properties of these analogues of natural 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in the multilamellar form. Both the Sp and RP + Sp isomers showed a "pretransition" (Tpt = 43.7 and 43.8 OC, respectively) and a "main transition" ( T , = 45.0 and 44.8 OC, respectively). The corresponding values for DPPC were 35.1 and 41 $5 OC, respectively. (Rp)-DPPsC, however, showed a single, broad transition at 45.9 OC with significantly higher AH. Addition of 15% (&)-DPPsC to the RP isomer converted the broad DSC trace to a "normal" pattern, with Tpt and T, at 42.8 and 44.7 OC, respectively. These suggest that the broad, highly endothermic transition is a unique property of pure (Rp)-DPPsC, which could be a superposition of subtransition, pretransition, and main transition based on the following results. While (Sp)-and (RP + Sp)-DPPsC showed a subtransition near 20 OC following prolonged incubation at 0 OC, a property also possessed by DPPC, (Rp)-DPPsC showed no discernible subtransition following incubation at 0 OC. Furthermore, it was found that (Rp)-DPPsC can indeed exist in the gel phase but relaxes rapidly to a lower energy phase, presumably the subphase. The half-life of the metastable gel phase was found to increase with decreasing diastereomeric purity of (Rp)-DPPsC. These studies suggest that (Rp)-DPPsC is thermodynamically and kinetically more stable at the subphase and demonstrate that the structure and configuration at the phosphate group of phospholipids have a large effect on the thermotropic properties of membranes, particularly in the subtransition temperature. The results are discussed in terms of intermolecular interactions and chiral discrimination in phospholipid membranes.The effect of chirality on the molecular interactions of membranes has received increasing attention in recent years.' One important question is whether there are chiral discrimination factors in membranes, as their main constituents and many of the compounds which must traverse them are chiral. The general approach to determine "enantiomer discrimination" has been to compare the physical properties of isomerically pure phospholipids with those of the mixture of enantiomers. Arnett and co-workers have clearly demonstrated enantiomer discrimination in the monolayers of enantiomeric and racemic N-(a-methylbenzy1)-stearamide.'q3 Chiral discrimination between monolayers of enantiomeric and racemic phospholipids has also been reported in the force-area isotherms of monolayers of 1-stearoyl-2-lauroylph~sphatidylcholine~ and in the differential scanning calorimetry (DSC) studies of multilamellar DPPC5-' However, Arnett and Gold* have been unable to detect any significant difference between racemic DPPC and its enantiomers in their meticulous studies using DSC, NMR, and monolayer techniques. (1) For pa...

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

“…However, this assumption is not valid for lipids with more than one chiral center, where the 1,2-snand 2,3-sn-glycerol isomers are diastereomers instead of enantiomers. Indeed, the introduction of a second chiral center at phosphorus by replacing an oxygen with a sulfur atom produces diastereomers ofPC that differ significantly in the physical properties of their lamellar phases (23,24). Similar differences in gel-phase polymorphism have also been OR' FIGURE 1 The chemical structure of di-dodecyl-o-D-glucosyl glycerols used in this study.…”

“…Until recently, it was not known ifthe structures ofthe nonlamellar phases of PEs were dependent on the chirality ofthe glycerol backbone, but the latest measurements of 1,2-sn and racemic dimethyl dihexadecylphosphatidylethanolamine (DHPE) at low water content were unable to detect differences in either the structure or dimensions of the cubic phase formed (27). To date, however, there have been no studies of the physical properties of diastereomeric thio-PEs similar to those of the thio-PCs (23,24). Thus, with glyceroglycolipids, which are known to form both lamellar and nonlamellar structures, the addition of a chiral center at C5 of each sugar molecule might be expected to produce differences in the physical properties of the 1,2-sn and 2,3-sn glycerol isomers.…”

Phospholipids chiral at phosphorus. Dramatic effects of phosphorous chirality on the deuterium NMR properties of the choline head group of phospholipids in the liquid crystalline phase

“…The isomeric purity was >98% in all cases as judged by 3IP NMR. The samples were repetitively purified by precipitating from acetone/ethanol (10/1) until their DSC traces are identical with those described by Wisner et al (1986).…”

“…This stereochemical approach has led us to demonstrate that the phosphate group of phospholipids is involved in the interaction with phospholipase A2 even though it is not directly involved in the reaction (Bruzik et al, 1983;Tsai et al, 1985) and that the same interaction is absent in a functionally related enzyme lecithin-cholesterol acyltransferase (Rosario-Jansen et al, 1990). Applying this approach to the biophysical properties of lipid bilayers, we have shown that the Rp isomer of DPPsC is unusually stable in the subgel phase on the basis of DSC (Wisner et al, 1986), X-ray diffraction, 31P NMR, and FT-IR studies (Sarvis et al, 1988). The FT-IR results also reveal that a key structural feature that could be related to the stable subgel phase of (Rp)-DPPsC is that its C=0 stretching band is asymmetric.…”

Chiral Phosphorothioates: Stereochemical Analysis of Enzymatic Substitution at Phosphorus

“…It was thereby shown that phospholipase A2 preferentially accepts (R,)-DPP,E as a substrate, whereas phospholipase C accepts (S,)-DPP,E. The chiral thiophospholipids have been used for analysis of the stereochemical course of phosphotransferase action by phospholipase D, as well as for comparative studies of their different properties in various physical states (57)(58)(59).…”