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...

Fourier-transform infrared spectroscopy (FT-IR) was used to study the structural properties of Rp, Sp, and Rp + Sp isomers of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC), in comparison with those of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). For the vibrational modes of acyl chains, isomers of DPPsC show similar temperature and phase dependence to DPPC. However, the Rp isomer of DPPsC exhibits several unique properties: the CH2 symmetric stretching band is unusually weak, the CH2 asymmetric stretching band is unusually narrow, and the CH2 wagging bands do not disappear completely at temperatures above the main transition. These differences could imply a tighter packing and be responsible for the unique phase-transition property of (Rp)-DPPsC. For the vibrational modes of the thiophosphodiester group, the frequency of the P-O stretching mode of DPPsC suggests that the POS- triad exists predominantly in the mesomeric form. This is in contrast to the structure of nucleoside phosphorothioates where charge localization at sulfur has been demonstrated [Iyengar, R., Eckstein, F., & Frey, P. A. (1984) J. Am. Chem. Soc. 106, 8309-8310]. This suggests that the different biophysical properties between isomers of DPPsC are not due to different charge distribution in the POS- triad or different geometry of charge distribution on the membrane surface. Instead, factors such as size or hydration property of oxygen and sulfur, as well as the different configuration at phosphorus, could be responsible for the differences in the conformation and packing of acyl chains, as revealed by the different properties in the CH2 stretching and wagging modes of DPPsC.

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A recent study using differential scanning calorimetry (DSC) showed that the thermotropic phase behavior of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC) is sensitive to the configuration at phosphorus and that the Rp isomer displayed only a broad transition at 45.6 degrees C [Wisner, D. A., Rosario-Jansen, T., & Tsai, M.-D. (1986) J. Am. Chem. Soc. 108, 8064-8068]. We have employed X-ray diffraction, 31P NMR, and Fourier transform infrared (FT-IR) spectroscopy to characterize various phases of the isomers of DPPsC, to compare the structural differences between 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and isomers of DPPsC, and to identify structural factors responsible for the unique behavior of the RP isomer. The results from all three techniques support the previous proposal based on DSC studies that (SP)- and (RP + SP)-DPPsC undergo a subtransition, a pretransition, and a main transition analogous to those of DPPC, while (RP)-DPPsC is quite stable at the subgel phase and undergoes a direct subgel----liquid-crystalline transition at 46 degrees C. Quantitative differences between DPPC and DPPsC (i.e., the effect of sulfur substitution rather than the configurational effect) in the subgel phase have also been observed in the chain spacing, the motional averaging, and the factor group splitting (revealed by X-ray diffraction, 31P NMR, and FT-IR, respectively). In particular, DPPsC isomers are motionally rigid and show enhanced factor group splitting in the subgel phase. These results suggest that DPPsC is packed in different subcells relative to DPPC in the subgel phase.(ABSTRACT TRUNCATED AT 250 WORDS)

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