Another Brick in the Wall of Tear Film Insights Added Through the Total Synthesis and Biophysical Profiling of anteiso-Branched Wax and Cholesteryl Esters.

The tear film lipid layer (TFLL) plays a vital part in maintenance of ocular health and represents a unique biological barrier comprising unusual and specialized lipid classes and species. The wax and cholesteryl esters (WEs and CEs) constitute roughly 80-90% of the TFLL. The majority of species in these lipid classes are branched and it is therefore surprising that the synthesis and properties of the second largest category of species, i.e., the anteiso-branched species, remain poorly characterized. In this study, we have developed a total synthesis route and completed a detailed NMR spectroscopic characterization of two common anteiso-branched species, namely: (22S)-22-methyltetracosanyl oleate and cholesteryl (22'S)-22'-methyltetracosanoate. In addition, we have studied their structural properties in the bulk state by wide-angle and small-angle X-ray scattering and their behavior at the aqueous interface using Langmuir monolayer techniques. A comparison to the properties displayed by iso-branched and straight-chain analogues indicate that branching patterns lead to distinct properties in the CE and WE lipid classes. Overall, this study complements the previous work in the field and adds another important brick in the tear film insights wall.

A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer.

BACKGROUND: An amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model. MATERIALS AND METHODS: The transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays. RESULTS: The transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection. CONCLUSION: Chol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response.

Self-assemblies of 5'-cholesteryl-ethyl-phosphoryl zidovudine.

Anti-HIV prodrugs are recently focused on due to their ability of self-assembly, macrophage targeting, and enhanced antiviral effects. Here, an amphiphilic prodrug of zidovudine, an anti-HIV nucleoside analogue, 5'-cholesteryl-ethyl-phosphoryl zidovudine (CEPZ) was synthesized. CEPZ showed some unique physicochemical properties. The solubility of CEPZ in the noncompetitive solvents chloroform and tetrahydrofuran (THF) was very high based on the hydrogen bonds between zidovudine groups, though CEPZ was sparing soluble in alcohols and almost insoluble in water. The typical amphiphilic property of CEPZ was demonstrated according to the Langmuir monolayers at the air/water interface. The LogP of CEPZ was high to 13.78, indicating the high hydrophobicity of amphiphilic CEPZ similar to phospholipids. Homogenous and stable self-assemblies were formed with the mean size of 128.7nm and the zeta potential of -35.4mV after injecting the CEPZ-in-THF solution into water. Hydrophobic interaction between the cholesteryl moieties of CEPZ could drive molecular self-assembly and lead to the formation of spherical vesicles. CEPZ self-assemblies showed strong stability even under high temperature and gravity probably due to the high surface charge. CEPZ was very slowly degraded in neutral solutions (e.g., pH 7.4), but fast in acid solutions (e.g., pH 5.0) and some tissue homogenates. CEPZ was quickly eliminated from the circulation and distributed into the mononuclear phagocyte system (MPS) including the liver, spleen and lung after bolus intravenous administration of CEPZ self-assemblies to mice. The MPS targeting effect of CEPZ self-assemblies makes them become a promising self-assembled drug delivery system to eradicate the HIV hidden in the macrophages.

Synthesis of (2ß,3α,6-²H3cholesteryl linoleate and cholesteryl oleate as internal standards for mass spectrometry.

The accurate analysis of trace component in complex biological matrices requires the use of reliable standards. For liquid chromatography/mass spectrometry analysis, the stable isotope-labeled derivatives of the analyte molecules are the most appropriate internal standards. We report here the synthesis of (2ß,3α,6-(2)H3)cholesteryl linoleate and oleate containing three non-exchangeable deuterium in the steroid ring. The principal reactions used were: (1) trans diaxial opening of 2α,3α-epoxy-6-oxo-5α-cholestane with LiAlD4 and subsequent oxidation of the resulting (2ß,6α-(2)H2)-3α,6ß-diol with Jones' reagent, followed by reduction of the resulting (2ß-(2)H)-3,6-dione with NaBD4 leading to the (2ß,3α,6α-(2)H3)-3ß,6ß-dihydroxy-5α-cholestane, (2) selective protection of the 3ß-hydroxy group as the tert-butyldimethylsilyl ether, (3) dehydration of the 6ß-hydroxy group with POCl3 and removal of tert-butyldimethylsilyloxy groups with 5M HCl in acetone, and (4) esterification of the resultant (2ß,3α,6-(2)H3)cholesterol with linoleic and oleic acids using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. The isotopic purity was found to be satisfactory by mass spectrometry, and nuclear magnetic resonance properties of the new compounds were tabulated. The labeled compounds can be used as internal standards in liquid chromatography/mass spectrometry assays for clinical and biochemical studies.

Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives.

Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3ß'-Acetoxy-5ß'-hydroxy-6'-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.

Design and evaluation of pH-sensitive liposomes constructed by poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate for doxorubicin delivery.

In this study, a novel material, poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (PEtOz-CHEMS), was synthesized to construct pH-sensitive liposomes. The structure of PEtOz-CHEMS was confirmed by thin-layer chromatography, Fourier transform infrared spectroscopy, and (1)H NMR. Anticancer fluorescent drug doxorubicin (DOX) was encapsulated into the liposomes. Compared with conventional liposomes (CL), CHEMS modified liposomes (CH-L) and PEGylated liposomes (PEG-L), the PEtOzylated liposomes (PEtOz-L) showed an acidic pH-induced increase in particle size. At pH 6.4, the heme release of PEtOz-L group was close to that of the positive control group, whereas that of CL, CH-L and PEG-L was close to that of the negative control group. In vitro drug release studies demonstrated that DOX was released from PEtOz-L in a pH-dependent manner, and the release of DOX from conventional DOX liposomes (CL-DOX), DOX loaded CH-L (CH-DOX-L) and PEGylated DOX liposomes (PEG-DOX-L) had no pronounced differences under each pH medium. In vitro cellular uptake assays showed that PEtOz-DOX-L indicated a significant fluorescence intensity at pH 6.4 compared with at pH 7.4. CL-DOX, CH-DOX-L and PEG-DOX-L did not achieve any obvious diversity at different pH conditions. Confocal laser scanning microscopy images showed that PEtOz-DOX-L can fuse with the endosomal membrane under acidic conditions of endosome, release DOX into the cytoplasm, then gather into the nucleus. Therefore, PEtOz can help liposomes achieve "endosomal escape". The in vitro cytotoxicity experiment results on A375 cells showed that PEtOz-DOX-L resulted in lower cell viability than CL-DOX, CH-DOX-L and PEG-DOX-L under low pH conditions. These results confirm that the pH-responsive PEtOz was a promising material for intracellular targeted delivery system and might be used for overcoming the "PEG dilemma".

Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3ß,25-diol, disulfate.

Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3ß, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages or HepG2 cells significantly inhibited cholesterol synthesis and markedly decreased lipid levels in vivo in NAFLD mouse models. RT-PCR showed that 25HCDS significantly decreased SREBP-1/2 activities by suppressing expression of their responding genes, including ACC, FAS, and HMG-CoA reductase. Analysis of lipid profiles in the liver tissues showed that administration of 25HCDS significantly decreased cholesterol, free fatty acids, and triglycerides by 30, 25, and 20%, respectively. The results suggest that 25HCDS inhibits lipid biosynthesis via blocking SREBP signaling. We conclude that 25HCDS is a potent regulator of lipid metabolism and propose its biosynthetic pathway.

Synthesis and properties of cholesteryl 4-(Alkanoylamino)benzoates: liquid crystals and organogelators.

As a new liquid crystal and organogelator, cholesteryl 4-(alkanoylamino)benzoates were prepared. Cholesteryl 4-(alkanoylamino)benzoates had enantiotropic cholesteric and chiral smectic C phases. Furthermore cholesteryl 4-(alkanoylamino)benzoates gelled organic liquid such as 1-decanol, linalool, geraniol, nerol, citronellol, linalyl acetate, lavender oil, orange oil, and rose oil. The terpene and perfume gels show good release characteristics of the volatile components for a long period.

Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel.

In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery.

Synthesis of a cholesteryl-HEG phosphoramidite derivative and its application to lipid-conjugates of the anti-HIV 5'TGGGAG³' Hotoda's sequence.

A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG³' oligomer, known as the Hotoda's sequence, to produce new potential anti-HIV agents.

Well-defined cholesterol polymers with pH-controlled membrane switching activity.

Cholesterol has been used as an effective component of therapeutic delivery systems because of its ability to cross cellular membranes. Considering this, well-defined copolymers of methacrylic acid and cholesteryl methacrylate, poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA), were generated as potential delivery system components for pH-controlled intracellular delivery of therapeutics. Statistical copolymers with varying cholesterol contents (2, 4, and 8 mol %) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the copolymers in aqueous solutions ranged from 5 ± 0.3 to 7 ± 0.4 nm for the copolymers having 2 and 4 mol % CMA and 8 ± 1.1 to 13 ± 1.9 nm for the copolymer having 8 mol % CMA with increasing pH (pH 4.5-7.4). Atomic force microscopy (AFM) analysis revealed that the copolymer having 8 mol % CMA formed supramolecular assemblies while the copolymers having 2 and 4 mol % CMA existed as unimers in aqueous solution. The pH-responsive behavior of the copolymers was investigated via UV-visible spectroscopy revealing phase transitions at pH 3.9 for 2 mol % CMA, pH 4.7 for 4 mol % CMA, and pH 5.4 for 8 mol % CMA. Lipid bilayers and liposomes as models for cellular membranes were generated to probe their interactions with the synthesized copolymers. The interactions were determined in a pH-dependent manner (at pH 5.0 and 7.4) using surface plasmon resonance (SPR) spectroscopy and liposome leakage assay. Both the SPR analyses and liposome leakage assays indicated that the copolymer containing 2 mol % CMA displayed the greatest polymer-lipid interactions at pH 5.0, presenting the highest binding ability to the lipid bilayer surfaces, and also demonstrating the highest membrane destabilization activity. CellTiter-Blue assay showed that the copolymers did not affect the cell viability up to 30 µM over a period of 72 h.

Synthesis of monomethoxypolyethyleneglycol-cholesteryl ester and effect of its incorporation in liposomes.

The objective of the present study was to synthesize monomethoxypolyethyleneglycol-5000 cholesteryl ester [PEG-CH] as a cost-effective substitute for polyethyleneglycol-phosphatidylethanolamine and to evaluate the influence of its incorporation in liposomal bilayers for surface modification. PEG-CH was synthesized and characterized by infrared (IR), proton nuclear magnetic resonance spectroscopy ((1)H NMR), and differential scanning calorimetry (DSC) studies. Influence of incorporation of PEG-CH in liposomes was evaluated on various parameters such as zeta potential, DSC, and encapsulation efficiency of a hydrophilic drug pentoxyfylline. Conventional and PEG-CH containing pentoxyfylline liposomes were formulated and their stability was evaluated at 4°C for 3 months. PEG-CH could be successfully synthesized with good yields and the structure was confirmed by IR, DSC, and (1)H NMR. The incorporation of PEG-CH in liposomes resulted in reduction of the zeta potential and broadening of the DSC endotherm. Furthermore, incorporation of PEG-CH in liposomes decreased the encapsulation efficiency of pentoxifylline in liposomes when compared to conventional liposomes. Conventional and PEG-CH containing pentoxyfylline liposomes did not show any signs of pentoxyfylline degradation when stored at 4°C for 3 months.

Lipid markers of "geometrical" radical stress: synthesis of monotrans cholesteryl ester isomers and detection in human plasma.

Heteroatom-centered free radicals are able to transform cis unsaturated fatty acids to the thermodynamically more stable, but unnatural, trans configuration. The "geometrical" radical stress can be estimated in biological samples using trans fatty acid isomers as lipid markers. Regioselectivity is an important feature of the "geometrical" radical stress, because the supramolecular organization of the polyunsaturated fatty acid moieties of phospholipids can lead to preferential monotrans isomer formation. The regioisomer recognition is a crucial step, which is helped by appropriate molecular libraries available through radical-based synthetic methodologies. Cholesteryl linoleate and arachidonate esters are interesting targets for their biochemical connection with membrane phospholipid turnover and their well-known roles in cardiovascular health. The synthesis of monotrans isomers of PUFA cholesteryl esters was achieved by a thiyl radical-catalyzed cis-trans isomerization. Valuable NMR, IR, and Raman spectroscopic data have been collected for promising application in metabolomics and lipidomics. The identification of monotrans cholesteryl ester isomers was carried out in human plasma by GC, Raman, and IR analyses, demonstrating for the first time the presence of specific regiosiomers connected to free radical stress. This work helps to highlight the chemical biology approach for the access to molecular libraries applicable to biomarker development, and the cis-trans isomerization as a relevant process to be integrated in the puzzling scenario of free radical-mediated lipid modifications.

Syntheses of chitin-based imprinting polymers and their binding properties for cholesterol.

A novel chitin derivative, cholesteryl chitin carbonate (Chitin-Chol), was synthesized from chitin and cholesteryl chloroformate. This product was characterized by Fourier transform infrared (FTIR) spectroscopy and solid-state ¹³C nuclear magnetic resonance (¹³C NMR), and was used as a covalently bound template precursor for imprinting cholesterol. After cross-linking with toluene 2,4-diisocyanate, it was efficiently cleaved hydrolytically to afford a guest-binding site accompanying the easy and efficient removal of a sacrificial spacer. The selectivity and efficacy of a chitin-based imprinting polymer for steroid binding were assessed by a chromatographic screening process. The results of binding experiments showed that this molecular imprinting polymer (MIP) has a high binding capacity with cholesterol. The target discrimination towards cholesterol over its close structural analogue suggested that the polymer recognition site was possible on the basis of the inversion of configuration of a single hydroxyl group. In addition, non-covalent imprinting was done using chitin as a precursor and its binding properties for cholesterol were also evaluated.

Macrophage activation induces formation of the anti-inflammatory lipid cholesteryl-nitrolinoleate.

Nitroalkene derivatives of fatty acids act as adaptive, anti-inflammatory signalling mediators, based on their high-affinity PPARgamma (peroxisome-proliferator-activated receptor gamma) ligand activity and electrophilic reactivity with proteins, including transcription factors. Although free or esterified lipid nitroalkene derivatives have been detected in human plasma and urine, their generation by inflammatory stimuli has not been reported. In the present study, we show increased nitration of cholesteryl-linoleate by activated murine J774.1 macrophages, yielding the mononitrated nitroalkene CLNO2 (cholesteryl-nitrolinoleate). CLNO2 levels were found to increase approximately 20-fold 24 h after macrophage activation with Escherichia coli lipopolysaccharide plus interferon-gamma; this response was concurrent with an increase in the expression of NOS2 (inducible nitric oxide synthase) and was inhibited by the (*)NO (nitric oxide) inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester). Macrophage (J774.1 and bone-marrow-derived cells) inflammatory responses were suppressed when activated in the presence of CLNO2 or LNO2 (nitrolinoleate). This included: (i) inhibition of NOS2 expression and cytokine secretion through PPARgamma and *NO-independent mechanisms; (ii) induction of haem oxygenase-1 expression; and (iii) inhibition of NF-kappaB (nuclear factor kappaB) activation. Overall, these results suggest that lipid nitration occurs as part of the response of macrophages to inflammatory stimuli involving NOS2 induction and that these by-products of nitro-oxidative reactions may act as novel adaptive down-regulators of inflammatory responses.

A facile synthesis of C-24 and C-25 oxysterols by in situ generated ethyl(trifluoromethyl)dioxirane.

Experiments were performed to compare the regioselective hydroxylation of the isopropyl C-H bond at C-25 in 5alpha-cholestan-3beta-yl acetate by in situ generated dimethyldioxirane, methyl(trifluoromethyl)dioxirane, hexafluoro(dimethyl)dioxirane or ethyl(trifluoromethyl)dioxirane (ETDO). The dioxiranes were generated from the corresponding ketones and potassium peroxymonosulfate in aq. NaHCO(3), pH 7.5-8.0. Of the four dioxiranes examined, partially fluorinated, sterically bulky ETDO displayed the highest reactivity and regioselectivity. Using in situ generated ETDO, a facile, synthesis was developed for two naturally occurring oxysterols, i.e., 25-hydroxycholesterol, as well as its 3-sulfate (overall yield of the sulfate, 24%) and 24-oxocholesterol (16%), starting from cholesterol.

Bavachin and isobavachalcone, acyl-coenzyme A: cholesterol acyltransferase inhibitors from Psoralea corylifolia.

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. Ethanol extract of Psoralea corylifolia showed a significant inhibition of ACAT enzyme. Via bioactivity-guided fractionation of the ethanol extract of Psoralea corylifolia, two prenylated flavonoids were isolated. Their structures were determined as bavachin (1) and isobavachalcone (2) by spectroscopic analysis ((1)H-, (13)C-NMR, 2DNMR, and ESI-MS). The IC(50) values were 86.0 (1) and 48.0 (2) microM in the ACAT assay system using rat liver microsome. Compound 2 also decreased cholesteryl ester formations in HepG2 cells. In addition, this compound showed a noncompetitive type of inhibition of ACAT.

Characterization of novel cholesterol esterase from Trichoderma sp. AS59 with high ability to synthesize steryl esters.

A novel cholesterol esterase with there and throughout to synthesisze steryl ester was obtained from the culture filtrate of a fungal strain Trichoderma sp. AS59 isolated from soil. The extracellular enzyme was a monomeric protein with a molecular mass of approximately 58 kDa and an isoelectric point of 4.3. The optimal temperature was between 35 degrees C and 40 degrees C, and the optimal pH was 7.0. The enzyme retained 75% of the initial activity after 18 h of incubation at 30 degrees C in the pH range of 3.5-7.5. Its relative hydrolytic activities on fatty acid cholesteryl esters were in the following order: butyrate (121%), linoleate (100%), caprylate (79%), myristate (42%), palmitate (38%), caproate (37%), and laurate (35%). Unlike mammalian pancreatic cholesterol esterase that is activated by primary cholates on hydrolysis of long-chain fatty acid cholesteryl esters, the enzyme from Trichoderma sp. AS59 displayed its basal activity and was not affected by cholate up to a concentration of 5 mM. At higher cholate concentrations the activity gradually decreased, but reincreased at about 40 mM to reach more than twice the basal activity at 100 mM. The enzyme exhibited a broad substrate specificity, being capable of hydrolyzing various fatty acid esters of not only cholesterol, but also methanol, glycerol, and p-nitrophenol. When incubated with a mixture of cholesterol and oleic acid of equal amounts, the enzyme achieved stoichiometrical esterification in 5 h, indicating its potential utility in food additives and liquid crystal devices.

Ionic polymeric amphiphiles with cholesterol mesogen: adsorption and organization characteristics at the air/water interface from Langmuir film balance studies.

Ionic polymeric amphiphiles consisting of cholesterol mesogen were investigated for the interfacial adsorption characteristics at the air/water interface using a Langmuir film balance with an aim to understand the influence of ionic segment from 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) on the packing behavior of cholesterol at the interface. From surface pressure (pi)-area (A) isotherm characteristics, it is demonstrated that the homopolymer and the copolymer C consisting of 0.15 mol fraction CAB segments exhibit the most expanded structures contributing to surface area of about 84 A(2)/molecule. It is shown that the copolymer B with 0.1 mol fraction CAB provides optimum hydrophilic liphophilic balance to form the most compact structures contributing to a surface area of 35.75 A(2)/molecule. The high surface pressure, >40 mN/m, in contrast to that of PAMPS demonstrates significant adsorption of the copolymers at the interface. An interesting correlation among interfacial packing characteristics, thermal behavior, and solution structures is demonstrated. From molecular models developed for CAB, it is shown that the horizontal orientation of the linker group with respect to cholesterol chain in CAB underlies the expanded structures observed in PCAB and copolymer C.

New dicholesteryl-based gelators: chirality and spacer length effect.

Eight new diacid amides of dicholesteryl L(D)-alaninates were designed and prepared. The compounds with spacers containing three, four, five, or six carbon atoms and L-alanine residues are denoted as 1a, 2a, 3a, and 4a, respectively, and those containing D-alanine residues are denoted as 1b, 2b, 3b, and 4b, respectively. A gelation test revealed that a subtle change in the length of the spacer and an inverse in the chirality of the amino acid residue can produce a dramatic change in the gelation behavior of the compounds and the microstructures of the gels, as revealed by SEM, XRD, and CD measurements. Importantly, for the compounds 1 and 2, those containing d-alanine residues (1b, 2b) are more efficient gelators than their analogues with opposite chirality (1a, 2a). For the compounds of longer spacers (3, 4), however, those containing l-alanine residues (3a, 4a) are superior to the corresponding ones with d-alanine residues (3b, 4b). Very interestingly, of the 139 gel systems studied, at least 11 of them gel spontaneously at room temperature. Studies of the rheological properties of the example systems of these gels demonstrated that change in the spacer lengths of the gelators has a great effect upon the mechanical properties of the corresponding gels, and the studies also revealed the thixotropic properties of the gels. Furthermore, it was observed that 4a forms water-in-oil gel emulsions with some organic solvents by simple agitating the systems at room temperature.