Novel thermal phase transition behavior of phosphatidylcholine analogs containing 1,2,4 - butanetriol as their backbone

Abstract

The sn-glycerol moiety in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was replaced by the rac-1,2,4-butanetriol residue, and the aqueous dispersions of the resulting DPPC analogs, viz. 1,2-dihexadecanoyloxy-rac-but-4-yl-[2-(trimethylammonium)ethyl]phosphate (1,2-bPC) and 1,3-dihexadecanoyloxy-rac-but-4-yl-[2-(trimethylammonium)ethyl]phosphate (1,3-bPC), were characterized by differential scanning calorimetry (DSC) and fluorescence polarization technique. Also, the corresponding (3R)-isomer of 1,3-bPC (1,3-(3R)bPC) was prepared and characterized by DSC. While the thermal phase transition properties of 1,2-bPC were similar to that of racemic DPPC, 1,3-bPC in identical conditions showed an abnormal property by exhibiting a metastable phase behavior at about 15° C. This abnormal property was associated only with the racemic mixture and was completely absent in its 3R-isomer. 1,3-(3R)bPC, unlike DPPC, showed only two high enthalpy transitions at about 29.7° C (Δ H, 7.45 kcal/mol) and 35.3° C (Δ H, 6.93 kcal/mol). These results clearly demonstrate that an insertion of one additional methylene residue between the glycerol C1 and C2 carbons in DPPC markedly alters its thermal phase transitional properties, whereas these properties remain virtually unchanged if a similar chemical change is introduced between the glycerol C2 and C3 carbon atoms.