Supramolecular assemblies of polymerizable phospholipids.

Abstract

Novel polymerizable ether lipids, 1,2-O-bis[10-(2',4'-hexadienoyloxy)decyl]-rac, 1,2-O-bis(10,12-tricosadiynyl)-rac, and (S)-2,3-O-bis(10,12-tricosadiynyl)-sn-glycero-1-phosphocholine (PC), were successfully synthesized. Differential scanning calorimetry (DSC) showed that the gel to liquid crystalline phase transition of the ether lipid bilayers occurs at 11.4, 27.6, and 30.0°C (T(m)), respectively. The T(m) of the saturated analogs of the sorbyl ether and ester lipids, which were synthesized for the study of lipid phase behavior, were -15.4 and -7.5°C, respectively. The sorbyl and diacetylenic ether lipids in bilayers were readily polymerized with 254 nm light. The stability of sorbyl either lipid vesicles toward a detergent, Triton X-100, was somewhat enhanced by photopolymerization. The optically active diacetylenic ether lipid formed microtubules and helices which were observed by transmission electron and optical microscopy. Polymerizable ester lipids, 1-palmitoyl-2-(2-methylene)palmitoyl, 1,2-bis(2-methylenepalmitoyl), and 1-oleoyl-2-(2-methylene)palmitoyl PC were synthesized. The T(m) of these lipids were estimated to be 33.6, 25.3, and ∼-10°C, respectively, via DSC and X-ray diffraction. Thermal reaction of the mono-substituted lipid suspensions with a water-soluble initiator, azobis(2-amidinopropane) dihydrochloride (AAPD), yielded oligomers which were soluble in organic solvents. However, reaction of the bis-substituted ester lipid in bilayers produced cross-linked polymers which are not soluble in organic solvents. The ceiling temperature for the radical polymerization of these lipid systems appears to be near 70°C since the polymerization conversion at 60°C was greater than at 70°C. Finally, a polymerizable ester lipid, 1-oleoyl-2-(2-methylene)palmitoyl-sn-glycerol-3-phosphoethanolamine (PE) was synthesized. According to DSC and X-ray diffraction, this hydrated PE suspension undergoes the transition from the lamellar liquid crystalline to the nonlamellar inverted hexagonal (H(II)) phase at 45-50°C. This compound (T(m) = 11.6°C) is a promising candidate for future studies of the stabilization of the H(II) phase.