氟碳磷脂的合成及其脂质体的生成

合成了两种具有氟碳疏水性链的磷脂, 其极性部分分别为胆碱和磷酸根. 超声分散下, 上述两种磷脂均可形成腈质体, 以电子显微镜观察和动态光散射测定得到胆碱形成的脂质体的尺寸在32-37nm左右. 而对后者的光散射测定得出的尺寸较大并与溶液的pH值有关. 具有胆极性基的氟碳脂质体如同相应的碳氢磷脂一样, 具有包容水溶性受物的能力,但透光性更好. 从荧光探针的荧光强度对温度变化的研究指出, 在53℃左右胆碱型氟碳脂质体发生了相变.     

Liposome formation of selectively-polymerized diene-containing phospholipids and their postpolymerization

Small and large unilamellar liposomes composed of 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphorylcholine (DODPC) are prepared by sonication and extrusion, respectively. They are polymerized with water-insoluble radical initiator, azobis(isobutyronitrile) (AIBN) which can selectively polymerize diene groups in 1-acyl chains of the lipids. Polymerized liposomes are freeze-dried to obtain the polymerized liposome powder. There are two methods to redisperse lyophilized liposomes into water. The extrusion is an effective method to disperse them because the energy at extrusion is necessary only for redispersion, whereas the excess energy at sonication gives damage on liposome structure. There is no difference in stability between polymerized liposomes before and after redispersion with extrusion. DODPC polymers, obtained from free radical-initiated polymerization with AIBN, are linear and have polymerizable diene groups in 2-acyl chains. The liposome powder is therefore soluble in organic solvents. Reconstruction of polymerized liposomes is performed with lipid polymers having low or high molecular weight. The lipid polymers having high molecular weight provide stable large unilamellar liposomes by ethanol injection, but unstable small unilamellar liposomes are formed by sonication. The liposomes reconstructed from lipid polymers having low molecular weight are unstable regardless of their size. After reconstruction of liposomes selectively polymerized by AIBN, diene groups in 2-acyl chains are polymerized by water-soluble radical initiator or UV-irradiation to yield highly crosslinked structure. Their stability is improved remarkably by this postpolymerization.     

Synthesis of ether-linked fluorocarbon surfactants and their aggregational properties in organic solvents

A series of single- and double-tailed hydrocarbon-fluorocarbon (HF) surfactants were prepared to evaluate the effect of molecular structure on aggregate formation in organic solvents. The molecules were designed with ether linkages to permit facile syntheses of both sets of molecules. Solvent foaming studies were used to rapidly assess the surface-active properties of the surfactants, while dynamic light scattering provided quantitative critical micelle concentrations (CMC) and hydrodynamic radius (R(h)) measurements of the aggregates in solution. The single-tailed surfactants did not produce any foaming action in a number of hydrocarbon solvents, nor was any micellar formation observed up to 100 mM concentrations. Double-tailed surfactants, on the other hand, gave low CMC values in dodecane but with R(h) values that indicated a tight micelle structure. Bilayer formation was expected but not observed for these molecules, which is believed to be due to their unusual structural geometry, imparted by the glycerol backbone. No thermotropic liquid crystalline (LC) behavior was observed for any of the single- or double-tailed molecules. These data contrast with the known behavior of perfluorinated alkanes and other fluorinated surfactants, suggesting that the ether linkage plays an important role in the self-organizing behavior of these molecules.     

Synthesis of phospholipids containing perfluorooctyl group and their interfacial properties

Highly fluorinated single-chained and/or double-chained phospholipids containing the perfluorooctyl group as the terminal segment of hydrophobic chains and a phosphocholine moiety as the hydrophilic headgroup were synthesized in order to investigate the effect of fluorinated segments on the stability of phospholipid monolayers formed at the air-water interface. Judging from the equilibrium spreading pressures (π_es) of their monolayers at the air-water interface, all of the fluorinated phospholipids formed more stable monolayers than the corresponding non-fluorinated counterparts. In addition, the fluorinated double-chained phosphatidylcholine containing C-C triple bond (monoyne group) formed stable and fluid vesicle membranes in water, although the single-chained phospholipids did not form vesicle membranes but micellar solutions under the present conditions.     

Synthesis of novel fluorocarbon ether bibenzoxazole polymers

Novel fluorocarbon bis(o-aminophenol) monomers were synthesized by a multistep route from 1,3-diiodohexafluoropropane and 1,8-diiodohexadecafluorooctane. The acetic acid-promoted polycondensation of these monomers with fluorocarbon ether-diimidate esters led to linear, soluble fluorocarbon ether-bibenzoxazole polymers with inherent viscosities in the range of 0.10–0.94 dl/g^?1. Polymer structures were verified by elemental and infrared (IR) spectral analysis. Many of the polymers exhibited considerable crystallinity in which the crystalline melt temperatures ranged from 53 to 187°C, as determined by differential scanning calorimetry. Some polymers, however, were isolated as completely amorphous, rubbery gums that exhibited glass transition temperatures as low as ?31°C. Good thermooxidative stabilities were exhibited with onset of weight loss of the polymers during thermogravimetric analysis in an air atmosphere occurring in the 375–450°C range.     

Synthesis and physical–chemical properties of hydrolyzed nanosized mesoporous fluorocarbon materials and carbon–fluorocarbon composites

Hydrolysis of nanosized mesoporous superstoichiometric fluorocarbon material FS (CF_{1.20 ± 0.03}) and carbon–fluorocarbon nanocomposites NCFC (CF_{0.93 ± 0.03}) by 10% KOH in aqueous-alcohol solution was studied and yielded two new classes of the hydrolyzed fluorocarbon nanomaterials: hydroxofluorocarbon nano-material FS–OH of general formula sp³-C_1−yF_n−x(OH)_x (n = 1; x > 0.1, y ∼ 0.05–0.1) and carbon–hydroxofluorocarbon nanocomposites NCFC–OH of general formula sp²-C_m*sp³-C_1−yF_n−x(OH)_x (n = 1; x ∼ 0; y ∼ 0.1–0.2).FTIR and Raman studies of FS–OH and NCFC–OH materials have shown that hydrolysis of sp³-C–F-bonds in these materials leads a decrease of sp³-C–F amount and appearance of characteristic absorption bands for sp³-C–OHO, carboxyls and carbonyls, typical for oxidized graphites, carbon blacks and various soots. These phenomena, in combination with C,H,F-analyses for FS–OH and NCFC–OH products have allowed to state that hydrolysis of FS and NCFC in KOH solutions can be explained by the substitution reactions of surface sp³-C–F to sp³-C–OH and sp²>CO containing groups.Observed hydrolytic reactions are also accompanied with processes of the colored solutions origin (yellow – for FS and red-brown – for NCFC). These solutions have UV-VIS spectra identical to graphene oxide and graphitic acid.     

Synthesis and characterization of carbohydrate-based phospholipids

Novel carbohydrate-based phospholipids containing two saturated C(12) (dilauroyl ribo-phosphocholine) (DLRPC), C(14) (dimyristoyl ribo-phosphocholine) (DMRPC), and C(20) (diarachadonyl ribo-phosphocholine) (DARPC) carboxylic acid chains were synthesized. The physical properties of the supramolecular structures formed by these compounds were compared to those formed by their direct glycerol analogues dilauroyl phosphocholine (DLPC), dimyristoyl phosphocholine (DMPC), and diarachadonyl phosphocholine (DAPC). Modulated differential scanning calorimetry (MDSC) and X-ray diffraction data indicated that with chain lengths < or =14 carbons, the carbohydrate backbone increased the thermal stability of the bilayer below the phase-transition temperature (T(m)) as compared to the glycerol-based lipids. With longer chains (C(20)), the bilayer structure was destabilized as compared to glycerol-based lipids. NMR studies of a DMRPC vesicle dispersion reveal split choline headgroup signals and distinct magnetization transfer effects arising from the "inner" and "outer" surfaces of the bilayer vesicle. Modulated differential scanning calorimetry also demonstrated that glycerol- and carbohydrate-based lipids mix, as evidenced by a single intermediate T(m). In addition, carbohydrate-based lipid/cholesterol mixtures exhibited a decrease in enthalpy with an increase in cholesterol concentration. Unlike glycerol phospholipids, carbohydrate lipids were resistant to enzymatic degradation by phospholipase A(2) (PLA(2)).     

Design of liposomes containing photopolymerizable phospholipids for triggered release of contents

We describe a novel class of light-triggerable liposomes prepared from a photo-polymerizable phospholipid DC_8,9PC (1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) and DPPC (1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine). Exposure to UV (254 nm) radiation for 0–45 min at 25 °C resulted in photo-polymerization of DC_8,9PC in these liposomes and the release of an encapsulated fluorescent dye (calcein). Kinetics and extents of calcein release correlated with mol% of DC_8,9PC in the liposomes. Photopolymerization and calcein release occurred only from DPPC/DC_8,9PC but not from Egg PC/DC_8,9PC liposomes. Our data indicate that phase separation and packing of polymerizable lipids in the liposome bilayer are major determinants of photo-activation and triggered contents release.     

Dynamics of spontaneous vesicle formation in fluorocarbon and hydrocarbon surfactant mixtures

The spontaneous self-assembly of unilamellar vesicles was investigated by means of time-resolved synchrotron small-angle X-ray scattering. The self-assembly process was initiated by rapid mixing of anionic surfactant micelles with either zwitterionic or cationic surfactant micelles in equimolar ratio using a stopped-flow device. For the zwitteranionic systems, transient disklike mixed micelles are observed as structural intermediates prior to the onset of vesiculation. These disklike micelles display an exponential growth law, and above a critical size they close to form unilamellar vesicles. In the catanionic system, the earliest observable structures within the mixing time of 4 ms are unilamellar vesicles. Nevertheless, in both systems a narrow distribution of the vesicle size was observed at the initial stages of their formation. The subsequent evolution of the vesicle size distribution depends on the subtle differences in the bilayer composition and properties.     

Synthesis of modified ether phospholipids

A number of modified ether phospholipids with additional substituents in the 2 position of the C(1)-alkyl chain, 1-O-[2-(R,S)-hydroxyhexadecyl]-2-O-methyl-rac-glycero-3-phosphocholine, 1-O-[2-(R,S)-acetoxyhexadecyl]-2-O-methyl-rac-glycero-3-phosphocholine, 1-O-[2-(R,S)-hydroxyhexadecyl]-2-chloro-2-deoxy-rac-glycero-3-phosphocholine, and 1-O-[2-(R,S)-acetoxyhexadecyl]-2-chloro-2-deoxy-rac-glycero-3-phosphocholine, have been synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 974–978, May, 1995.We thank Dr. V. S. Pashkov for spectroscopic measurements and Dr. M. V. Anikin for spectroscopic measurements and scientific discussions.This work was partially supported by the Russian Foundation for Basic Research (Project No. 94-03-08166).     

Gamma-ray polymerization of phospholipids having diene or triene groups as liposomes

Small unilamellar liposomes were prepared in an aqueous medium by the sonication of phospholipids containing diene or triene groups in their hydrocarbon acyl chains. These liposomes were polymerized by gamma-ray irradiation. Conversion of polymerization was successively followed by UV spectrometry. Diene-type lipid liposomes were revealed for which a gamma-ray dose of 0.8 Mrad was required for complete polymerization and which were polymerized more easily than triene-type lipid liposomes. Triene-type lipids required 2.3 Mrad gamma ray to polymerize them completely. Contrary to UV-irradiation polymerization, there was no concentration dependence on the polymerization. Structure of the polymerized liposomes were confirmed by electron microscopy as small unilamellar liposomes. Study on the leakage of fluorescein from inner aqueous phase of the polymerized liposomes revealed that polymerized triene-type liposomes were relatively more stable than the polymerized diene-type liposomes.     

Chromatography of functionalized liposomes and their components

The antitumour drug 1-beta-D-arabinofuranosylcytosine (ara C) was acylated by means of oleic acid anhydride, resulting in the prodrug N4-oleoyl-ara C. Together with a lipophilic biotin derivative, this lipophilic prodrug was incorporated into the bilayer membrane of unilamellar liposomes prepared by means of the detergent dialysis method. On addition of these biotinylated prodrug-liposomes to an excess of avidin, biotin residues were complexed with avidin. The unreacted avidin was removed by chromatography on the Ultrogel AcA-22 column. The prodrug-liposome-avidin complex was coupled to biotinylated monoclonal antibodies through the free binding sites of the immobilized avidin. Unreacted antibodies were removed by chromatography on an Ultrogel AcA-22 column. In vitro, the liposome-antibody complexes selectively bound to cells which were recognized by the monoclonal antibodies linked to the liposomes. For this reason, a promising strategy towards a specific chemotherapy of cancer is expected.     

DSC and Raman study on the effect of lysozyme and bovine serum albumin on phospholipids liposomes

In this paper, the effect of increasing amounts of lysozyme (Lyso) and bovine serum albumin (BSA) on the behaviour of lecithin (DMPC) and cephalin (DMPE) liposomes was investigated by means of Raman and DSC techniques. The results showed that both proteins affected, but in a different way, both lecithin and cephalin liposomes. In the samples with lower Lyso concentrations (up to 2 % w/w), a small decrease on the main transition temperature (T _m) was observed, whereas T _m increased by further addition of Lyso (up to 15.0 % w/w). At the same time, an increase of about 20 % in the ΔH of the transition was observed. Pre-transition was also affected in a greater extent by protein presence. When BSA interacted with liposomes, a smaller increase in the T _m values was observed with a contemporary increase of about 8 % in the associated ΔH. The data suggested that the BSA–liposomes interaction involves only the external surface of the bilayer, excluding thus any penetration into the liposomal hydrophobic core. On the contrary, a partial penetration into the bilayer is suggested when Lyso is added to liposomes. Both considered proteins strengthened the overall bilayer structure of DMPC liposomes, suggesting a decrease in the membrane permeability. Moreover, Lyso secondary structure changed by interaction with liposomes, as demonstrated by the Raman spectra behaviour, in particular in the case of DMPE.     

Synthesis of amphiphilic polysiloxanes and their properties for formation of nano-aggregates

In this study, we prepared amphiphilic polysiloxanes by introduction of hydrophobic and hydrophilic parts into a water-soluble poly(3-aminopropyl)siloxane. Fatty acid (lauroyl, myristoyl, palmitoyl, and stearoyl) chlorides and gluconolactone were employed as the reactants for the hydrophobic and hydrophilic parts, respectively. The reaction of the poly(3-aminopropyl)siloxane with fatty acid chlorides was performed in water/DMF, followed by the reaction with gluconolactone in DMSO, giving the corresponding amphiphilic polysiloxanes. The results of the NMR spectra, SEM observations, and DLS measurements indicated the formation of nano-aggregates from the amphiphilic polysiloxanes in water. These analytical data also suggested that the structures and functionalities of the hydrophobic parts affected the formation properties of the nano-aggregates.     

Isolation of the phospholipids of the cotton plant and their composition

Summary The yields of the free and bound lipids of the seed kernels of cotton plants of varieties S-4727 and S-6029 have been determined by their successive treatment with selective solvent, and the total and fractional proportions of lipid phosphorus have been found.The phospholipids have been solated and their group composition has been determined; it has been established that the main components are phosphatidylcholines, phosphatidylinositols, and phosphatidylethanolamines, while polyglycerophosphatides, lysophosphatidylcholines, and unidentified polar phospholipid are present in small amounts.The fatty-acid compositions of the free and bound lipids and phospholipids have been studied.Institute of the Chemistry of Plant Substances, Academy of the Uzbek SSR. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 449–453, July–August, 1975.