Membrane-forming properties of gemini lipids possessing aromatic backbone between the hydrocarbon chains and the cationic headgroup

Membrane-forming properties of five new gemini cationic lipids possessing an aromatic backbone between the headgroup and hydrocarbon chains have been presented. These gemini lipids differ by the number of polymethylene units [-(CH(2))(n)-] between the cationic ammonium -[N(+)(CH(3))(2)]- headgroups. The membrane-forming properties of these gemini lipids have been studied in detail by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), high-sensitivity differential scanning calorimetry (DSC), Paldan fluorescence studies, and UV-vis absorption spectroscopy. The electron micrographs and dynamic light scattering of their aqueous suspensions confirmed the formation of vesicular-type aggregates. The vesicle sizes and morphologies were found to depend strongly on the n-value of the spacer. Information on the thermotropic and hydration properties of the resulting vesicles was obtained from differential scanning calorimetry and temperature-dependent Paldan fluorescence studies, respectively. Examination of the thermotropic phase-transition properties of the lipid aggregates revealed interesting features of these lipids, which were found to depend on the length of the spacer chain. Paldan fluorescence studies indicate that the membranes of the gemini lipids are less hydrated as compared to that of the monomeric counterpart in their solid-gel state. In contrast in their fluid, liquid-crystalline phase, the hydration of gemini lipid aggregates was found to depend strongly on the length of the spacer. UV-vis absorption studies suggest an apparent H-type aggregate formation in the gemini lipid membranes in the gel states. In fluid state of the lipid membranes, H-aggregate formation was found to be enhanced depending on the length of the spacer. Such an understanding of the properties upon membrane formation from this new class of gemini lipids will be useful for further development of related gene delivery systems.     

Thermotropic and hydration studies of membranes formed from gemini pseudoglyceryl lipids possessing polymethylene spacers

Membrane formation from gemini pseudoglyceryl lipids bearing n-C14H29 and n-C16H33 chains has been reported. These lipid aggregates have been characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), high sensitivity differential scanning calorimetry (DSC), and Paldan fluorescence studies. The length of the spacer between the cationic ammonium headgroups has been varied from -(CH2)3- (propandiyl) to -(CH2)12- (dodecandiyl) in these lipids. All gemini lipids were found to generate stable suspensions in aqueous media. Electron microscopic studies revealed the smaller size of the gemini lipid aggregates as compared to their monomeric lipid counterparts. DLS measurements showed that the gemini lipid suspensions with a -(CH2)8- spacer length were bigger in size than that of other analogues. DSC studies suggest the unusual behavior of the gemini lipids bearing -(CH2)3- propanediyl spacer based lipids. These observations were consistent irrespective of the hydrocarbon chain lengths of the lipids. Paldan fluorescence based hydration studies showed that the hexadecyl chain based gemini lipid aggregates bearing a -(CH2)12- spacer were the most hydrated in their gel states among all the gemini lipid series investigated herein.     

Interfacial dilational properties of anionic gemini surfactants with polymethylene spacers

The dilational properties of anionic gemini surfactants alkanediyl-α,ω-bis(m-octylphenoxy sulfonate) (C₈C_mC₈) with polymethylene spacers at the water–air and water–decane interfaces were investigated by oscillating barriers and interfacial tension relaxation methods. The influences of oscillating frequency and bulk concentration on the dilational properties were explored. The experimental results show that the linking spacer plays an important role in the interfacial dilational properties. The moduli pass through one maximum for all three gemini surfactants at both water–air and water–decane interfaces. However, the values of moduli at the water–air interface are obviously higher than those at the water–decane interface because the sublayer formed by spacer chains will be destroyed by the insertion of oil molecules. Moreover, with the increase of spacer length, the surface adsorption film becomes more viscous at high concentration, which can be attributed to the process involving the formation of the sublayer. On the other hand, the spacers of the adsorbed C₈C₆C₈ molecules will extend into the oil phase when the interface is compressed. As a result, the interfacial film becomes more elastic with the increase of spacer length at high concentration. The experimental results obtained by the interfacial tension relaxation measurements are in accord with those obtained by the oscillating barriers method.     

Synthesis of novel cationic lipids with fully or partially non-scissile linkages between the hydrocarbon chains and pseudoglyceryl backbone

Five novel cationic lipids with fully or partiallynon-scissile linkage regions between the pseudoglyceryl backbone and the hydrocarbon chains have been synthesized. The membrane-forming properties of these new lipids are briefly presented.     

Aggregation properties of cationic gemini surfactants with partially fluorinated spacers in aqueous solution

The aggregation properties of cationic gemini surfactants alkanediyl-alpha,omega-bis(dodecyldimethylammonium bromide), [C(12)H(25)(CH(3))(2)N(CH(2))(m)(CF(2))(n)(CH(2))(m))N(CH(3))(2)C(12)H(25)]Br(2) [where 2m + n = 12 and n = 0, 4, and 6; designated as 12-12-12, 12-12(C(4)(F))-12, and 12-12(C(6)(F))-12, respectively] have been studied by microcalorimetry, time-resolved fluorescence quenching, and electrical conductivity. Compared with a fully hydrocarbon spacer of 12-12-12, the fluorinated spacer with a lower ratio of CF(2) to CH(2) in 12-12(C(4)(F))-12 tends to disfavor the aggregation, leading to larger critical micelle concentration (cmc), lower micelle aggregation number (N), and less negative Gibbs free energy of micellization (DeltaG(mic)). However, the fluorinated spacer with a higher ratio of CF(2) to CH(2) in 12-12(C(6)(F))-12 may prompt the aggregation, resulting in lower cmc, higher N, and more negative DeltaG(mic). It is also noted that enthalpy change of micellization (DeltaH(mic)) for 12-12(C(4)(F))-12 is the most exothermic, but the values of DeltaH(mic) for 12-12-12 and 12-12(C(6)(F))-12 are almost the same. These results are rationalized in terms of competition among the enhanced hydrophobicity and the rigidity of the fluorinated spacer, and the variation of immiscibility of the fluorinated spacer with the hydrocarbon side chains.     

Nematic conformation of oxyethylene spacers involved in main-chain liquid crystals

²HNMR measurements were performed on main-chain dimer and polymer liquid crystals (LC) having oxyethylene (OE) spacers -(OCH₂CH₂)_xO-(x=2, 3). The orientational as well as conformational characteristics of these molecules have been investigated in bulk and in a nematic solution. The OE spacer was found to take spatial arrangements characteristics of the nematic phase. The nematic conformation of the spacer remains nearly invariant over a wide range of temperature and concentration. In these analyses, the ratio of the deuterium quadrupolar splittings Δν/Δν^R (Δν: spacer and Δν^R: mesogenic unit) provided an important information regarding the spatial configuration of molecules in the LC state. The results obtained in this study are consistent with our previous conclusion drawn on a series of main-chain LC oligomers and polymers comprising n-alkane spacers -O(CH₂)_nO- (n=9, 10).     

Synthesis and properties of new polybenzimidazoles and N-phenyl polybenzimidazoles with flexibilizing spacers on the polymer backbone

Several new polybenzimidazoles (PBIs) and N-phenyl PBIs were synthesized by high temperature solution polycondensation techniques. Three different tetramine hydrochlorides and one N-phenyl tetramine hydrochloride were condensed independently with p-phenylenedioxydiacetic acid (PDDA), 2,2′-[isopropylidene bis(p-phenyleneoxy)] diacetic acid (bisacid A₂) and 2,2′-[sulfonyl bis(p-phenyleneoxy)] diacetic acid (bisacid S) in polyphosphoric acid (PPA) at high temperatures. The polymers were obtained in 55–65% yield with inherent viscosities in the range 0.58–0.96 dL/g. Four model benzimidazoles (MBI) were also synthesized to confirm the formation of polybenzimidazoles. The PBIs and MBIs were characterized by infrared spectroscopy and elemental analysis. The properties of the polymers such as solubility, density, crystallinity, and thermal, thermoxidative, and isothermal stabilities were studied.     

Synthesis of linear and hyperbranched poly(etherketone)s containing flexible oxyethylene spacers

As an alternative to strong acid reaction media for the Friedel–Crafts acylation for a polymer‐forming reaction, a mild polyphosphoric acid (PPA) with optimized amount of phosphorous pentoxide (P₂O₅) has been tested for the polymerization of AB monomers 4‐(2‐phenoxyethoxy)benzoic acid and 3‐(2‐phenoxyethoxy)benzoic acid, and an AB₂ monomer 3,5‐bis(2‐phenoxyethoxy)benzoic acid. The reaction progress of AB₂ monomer was conveniently traced by FTIR spectroscopy monitoring aromatic ketone (C?O) stretching bands arisen from carboxylic acid groups at the chain ends and carbonyl groups in the backbone as a function of reaction time at 110 °C. The resultant linear and hyperbranched polymers containing flexible oxyethylene spacers, which were prone to be hydrolyzed in strong acids at elevated temperature, displayed high intrinsic viscosities. Thus, the reaction medium PPA/P₂O₅ mixture as an electrophilic substitution reaction was indeed benign not to depolymerize growing polymer molecules but strong enough for the direct generation of carbonium ion from carboxylic acid to promote efficient polymerization. The resultant hyperbranched poly(etherketone) (PEK) displayed the best solubility among samples. All PEKs showed good thermal stability; glass transition temperatures were in the range of 90–117 °C; 5% weight loss generally occurred at greater than 345 °C in air. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5112–5122, 2007     

Solubilizing and catalytic properties of supramolecular systems based on gemini surfactants

Quantitative parameters characterizing the aggregation behavior of dicationic surfactants of the 12-s-12 type in aqueous solutions were determined: critical micelle concentrations, aggregation numbers, and surface potentials. The effects of the spacer length of the surfactants on their solubilizing effect with respect to hydrophobic (dye Orange OT) and water-soluble (p-nitrophenol) spectral probes and on their ability to shift acid-base equilibria were studied. The kinetics of alkaline hydrolysis of p-nitrophenyl acetate and p-nitrophenyl caprinate in 12-s-12 solutions was studied by spectrophotometry. A correlation between the micellar catalytic effect and the surface potential of micelles was established. The pronounced substrate specificity was revealed: the maximum acceleration of hydrolysis is observed in solutions of 12-6-12, attaining 1760 times for p-nitrophenyl caprinate.     

Syntheses, transfection efficacy and cell toxicity properties of novel cholesterol-based gemini lipids having hydroxyethyl head group

We have synthesized five new cholesterol based gemini cationic lipids possessing hydroxyethyl (-CH(2)CH(2)OH) function on each head group, which differ in the length of the polymethylene spacer chain. These gemini lipids are important for gene delivery processes as they possess pre-optimized molecular features, e.g., cholesterol backbone, ether linkage and a variable spacer chain between both the headgroups of the gemini lipids. Cationic liposomes were prepared from each of these lipids individually and as a mixture of individual cationic gemini lipid and 1,2-dioleoyl phosphatidylethanolamine (DOPE). Each gemini lipid based formulation induced better transfection activity than that of their monomeric counterpart. One such gemini lipid with a -(CH(2))(12)- spacer, HG-12, showed dramatic increase in the mean fluorescence intensity due to the expression of green-fluorescence protein (GFP) in the presence of 10% FBS compared to the conditions where there was no serum. Other gemini lipids retained their gene transfection efficiency without any marked decrease in the presence of serum. The only exception was seen with the gemini with a -(CH(2))(3)- spacer, HG-3, which on gene transfection in the presence of 10% FBS lost ~70% of its transfection efficiency. Overall the gemini lipid with a -(CH(2))(5)- spacer, HG-5, showed the highest transfection activity at N/P (lipid/DNA) ratio of 0.5 and lipid : DOPE molar ratio of 2. Upon comparison of the relevant parameters, e.g., %-transfected cells, the amount of DNA transfected to each cell and %-cell viability all together against Lipofectamine 2000, one of the best commercial transfecting agents, the optimized lipid formulation based on DOPE/HG-5 was found to be comparable. In terms of its ability to induce gene-transfer in the presence of serum and shelf-life DOPE/HG-5 liposome was found to be superior to its commercial counterpart. Confocal imaging analysis confirmed that in the presence of 10% serum using a Lipid : DOPE of 1 : 4 and N/P charge ratio of 0.75 with 1.2 μg DNA per well, HG-5 is better than Lipofectamine 2000.     

Synthesis and properties of novel fluorinated polyurethane based on fluorinated gemini diol

In the current study, the novel fluorinated polyurethanes (FPUs) that contained the gemini branched fluoroether side groups on the hard segments were developed. In brief, to obtain these FPUs, a new class of fluorinated gemini diol with double‐branched fluoroether side groups was first synthesized and characterized by using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry. Subsequently, a series of FPUs were designed and prepared by using hexamethylene diisocyanate, poly (tetramethylene oxide glycol), 1,4‐butanediol, and fluorinated gemini diol. Analysis of the FPUs' surface properties from contact angle analysis indicated that the water contact angle increased from 81° to more than 120° when the content of fluorinated gemini diol was increased. Differential scanning calorimetry results revealed that introduction of fluorinated gemini dio decreased the T_g of FPUs, causing a better phase separation. Results from thermogravimetric analysis studies indicated the thermal stability of FPUs was improved. Scanning electron microscopy and energy dispersive X‐ray spectroscopy revealed that fluoroether groups migrate to and enrich on the outmost surface of FPUs.     

Synthesis and phase-transfer catalytic activity of crown ethers bound to microporous polystyrene resins by oxyethylene spacers

Crown ethers bound to microporous polystyrene resins by oxyethylene spacers were prepared by the reaction of monoazacrown ethers with 2-tosyloxyethoxymethylated or 2-(2-tosyloxyethoxy)ethoxymethylated polystyrene resins crosslinked with 2 mol % of divinylbenzene. The activity of the immobilized lariat crowns for halogen exchange reactions under triphase conditions has been studied as a function of catalyst structure, loading, substrate structure, reagent structure, and solvent. The lariat catalysts with extra oxygen donors in the spacer chain exhibited higher activity than the corresponding immobilized catalysts without the donors in the spacer. The increased activity of the catalyst containing 15-crown-5 unit and two extra donors for the reaction of 1-bromooctane with KI was concluded to result from the enhanced complexation with the K⁺ ion, induced by the cooperative coordination of the crown unit donors and the donors in the spacer chain. The recovered catalysts could be re-used without decrease in activity.     

L-lysine based gemini organogelators: their organogelation properties and thermally stable organogels

Novel gemini organogelators based on L-lysine, in which two L-lysine derivatives are linked by different alkylene chain lengths through the amide bond, have been simply and effectively synthesized, and their organogelation abilities and thermal stabilities have been investigated. In a series of L-lysine ethyl ester derivatives, the organogelation abilities decreased with increasing alkylene spacer length. In particular, bis(N(epsilon)-lauroyl-L-lysine ethyl ester) oxalyl amide is a good organogelator that gels most organic solvents such as alcohols, cyclic ethers, aromatic solvents and acetonitrile. Various oxalyl amide derivatives with different alkyl ester groups such as hexyl, decyl, dodecyl, 2-ethyl-1-hexyl and 3,5,5-trimethylhexyl also showed good organogelation abilities. Furthermore, it was found that the cyclohexane gels formed by some oxalyl amide derivatives have a high thermal stability.     

Adsorption of gemini surfactants with dodecyl side chains and different spacers, including partially fluorinated spacers, on different surfaces: neutron reflectometry results

Neutron reflectometry has been used to study the adsorption of two symmetrical cationic (dimethyl ammonium bromide) gemini surfactants with two C(12)H(25) chains and different partially fluorinated spacers at three different surfaces: air/water, hydrophilic silica/water, and hydrophobic (octadecyltricholorosilane (OTS))/water. In addition, the adsorption of purely hydrocarbon geminis with the same side chains and spacers of different lengths has been studied at the same two solid surfaces. The limiting close-packed areas for the two fluorocarbon geminis, C(12)-C(3)fC(6)C(3)-C(12) and C(12)-C(4)fC(4)C(4)-C(12), are 92 and 72 ± 4 at the hydrophilic silica surface, 81 and 89 ± 4 at OTS, and 137 and 106 ± 4 ?(2) at the air/water interface with decreases of 38 and 24% from air/water to the average solid value, respectively. These changes suggest that the packing at the air/water interface is inefficient, and this allows the extra hydrophobicity of the chain environment at the two solid surfaces to promote much more efficient packing. At the air/water interface, the fluorocarbon spacers are on average the fragments furthest away from the underlying water, further out than in the nearest comparable hydrocarbon gemini, C(12)-C(12)-C(12). This is the probable explanation of the much lower value of the area per molecule at the air/water interface of C(12)-C(4)fC(4)C(4)-C(12) compared to that of C(12)-C(12)-C(12). It is also the probable cause of the inefficient packing of the hydrocarbon side chains. At the more hydrophobic OTS surface the situation is reversed and the fluorocarbon spacers are now the furthest from the hydrophobic surface, further out than the spacer in C(12)-C(12)-C(12). This is an unusually large structural change that must be associated with the greatly improved packing at the OTS surface. The efficiency of the packing is also high for the hydrophilic surface, no doubt because the hydrocarbon chains can interact favorably in the adsorbed bilayer core. The values of the area per molecule obtained for the series of hydrocarbon geminis at the air/water, OTS/water and silica/water interfaces are respectively 139, 104, and 98 ± 4 ?(2) for C(12)-C(12)-C(12), 114, 106, and 94 ± 4 ?(2) for C(12)-C(10)-C(12), 104, 84, and 85 ± 4 ?(2) for C(12)-C(6)-C(12), and 78, 66, and 70 ± 3 ?(2) for C(12)-C(3)-C(12). The area per molecule is also about 20% less on average at the two solid surfaces than at the air/water interface. This can also be attributed to more efficient packing caused by the more favorable hydrophobic interactions possible at these two surfaces than at the air/water interface, again showing that the packing at the air/water interface is inefficient and probably resulting from the competition between spacer and chains, which will be most pronounced for the C(12) spacer.     

Novel extended tetrathiafulvalenes based on acetylenic spacers: synthesis and electronic properties

A selection of mono- and diacetylenic dithiafulvalenes was synthesized and employed for the construction of extended tetrathiafulvalenes (TTFs) with hexa-2,4-diyne-1,6-diylidene or deca-2,4,6,8-tetrayne-1,10-diylidene spacers between the two 1,3-dithiole rings. By stepwise acetylenic scaffolding using (E)-1,2-diethynylethene (DEE) building blocks, an extended TTF containing a total of 18 C(sp) and C(sp(2)) atoms in the spacer was prepared. The versatility of the acetylenic dithiafulvene modules was also established by the efficient synthesis of a thiophene-spaced TTF, employing a palladium-catalyzed cross-coupling reaction. The developed synthetic protocols allow functionalization of the extended TTFs in three general ways: with 1) peripheral substituents on the fulvalene cores, 2) alkynyl moieties laterally appended to the spacer, and 3) cobalt clusters involving acetylenic moieties. Strong chromophoric properties of the extended TTFs were revealed by linear and nonlinear optical spectroscopies. Extensive electrochemical studies and calculations on these compounds are also reported, as well as X-ray crystallographic analyses.     

磺化甜菜碱型双子表面活性剂的合成及性能

以N,N'-二甲基乙二胺为起始原料,合成了一类新型磺化甜菜碱型双子表面活性剂.通过红外光谱(IR)、核磁共振(~1H-NMR)对中间体及最终产物——磺化甜菜碱型两性离子双子表面活性剂的分子结构进行了表征.对合成产物的表面性能及相关物性参数作了初步的研究.实验表明:合成制得的磺化甜菜碱型双子表面活性剂具有优异的表面活性,最低的表面张力可降至27.81 mN/m,且有着良好的乳化性能.     

Synthesis of novel dimeric cationic lipids based on an aromatic backbone between the hydrocarbon chains and headgroup

Seven dimeric cationic lipids possessing an aromatic anchor between the hydrocarbon chains and cationic headgroup have been synthesized. The spacers in these lipids vary in length, hydrophobicity and flexibility. The synthesis, membrane-forming properties and complexation with plasmid DNA (lipoplex formation) are briefly described.     

Interfacial assemblies of cyanine dyes and gemini amphiphiles with rigid spacers: regulation and interconversion of the aggregates

A series of gemini amphiphiles with a pyridinium headgroup and rigid spacers were designed, and their interfacial assemblies with cyanine dyes, 3,3-disulfopropyl-9-methyl-selenacarbocyanine (SeCy) and 3,3-disulfopropyl-4,5,4',5'-dibenzo-9-methyl-thiocarbocyanine (MTC), through the air/water interface were investigated. Although the dyes have intrinsic tendencies to form J- or H-aggregates in aqueous solutions, their aggregation could be regulated in the complex films. Depending on the spacer, both J- and H-aggregates were formed for SeCy, whereas an H-aggregate with different absorption bands was obtained for MTC. Furthermore, the formed aggregates in the films could be reversibly switched by treating the complex films with HCl, NH3 gas, or water vapor. The J-aggregates of SeCy could be changed into H-aggregates and recovered through an alternative HCl/NH3 exposure in the films. The H-aggregate of the MTC film could be changed into J-aggregate upon exposure to HCl gas and subsequently put into air or NH 3 gas, and the thus-formed J-aggregate could be changed into H-aggregate under hot water vapor. In addition, such a reversible switch between different aggregates of MTC was only observed when the gemini amphiphiles with rigid spacers were applied. A possible explanation related to the protonation of the dye and the reorganizations in the film during the interconversion between different aggregates was proposed.     

Design and interfacial assembly of a new series of gemini amphiphiles with hydrophilic poly(ethyleneamine) spacers

A new series of gemini amphiphiles containing two Schiff base moieties linked by the poly(ethyleneamine) with different lengths were designed, and their interfacial assemblies were investigated. Condensed monolayers were obtained on nearly neutral subphase where the hydrophilic spacers were found to immerse into the subphase. On strong alkaline and acidic subphase, the headgroup and the spacer of the gemini amphiphiles underwent dissociation and protonation, respectively, resulting in the enlargement of the molecular areas. Flat and uniform domains were obtained for the monolayers from nearly neutral subphase; flower-like or dendritic domains were observed for the films transferred from strong acidic subphase. On the other hand, when an anionic tetrakis(4-sulfonatonphenyl)porphine (TPPS) was added into an acidic subphase, an in situ complex formation between the gemini amphiphiles and TPPS occurred. The complex monolayers were transferred onto solid substrate and TPPS existed predominantly as J-aggregate in the complex films. Due to the multisited positive charges in the spacer on acidic subphase, the complex films of gemini amphiphiles with TPPS appeared as short fiber or nanorod structures and formed two-dimensional (2D) conglomerate chiral domains.     

Effect of backbone structures on photovoltaic properties in naphthodithiophene‐based copolymers

A “zigzag” naphthodithiophene‐based copolymer, poly[4,9‐bis(2‐ethylhexyloxy)naphtho[1,2‐b:5,6‐b′]dithiophene‐2,7‐diyl‐alt‐1,3‐(5‐heptadecan‐9‐yl)‐4H‐thieno[3,4‐c]pyrrole‐4,6‐dione] (P1) is synthesized and its properties are compared to “linear” naphthodithiophene‐based copolymer, poly[4,9‐bis(2‐ethylhexyloxy)naphtho[2,3‐b:6,7‐d′]dithiophene‐2,7‐diyl‐alt‐1,3‐(5‐heptadecan‐9‐yl)‐4H‐thieno[3,4‐c]pyrrole‐4,6‐dione] (P2). The field‐effect carrier mobilities and the optical, electrochemical, and photovoltaic properties of the copolymers are systematically investigated. The results suggest that the backbone of the copolymer structure significantly influences the band gap, electronic energy levels, carrier mobilities, and photovoltaic properties of the resultant thin films. In this work, the zigzag naphtho[1,2‐b:5,6‐b′]dithiophene‐based copolymer displays a good hole mobility and a high open‐circuit voltage; however, polymer solar cells in which the linear naphtho[2,3‐b;6,7‐d′]dithiophene‐based copolymer is used as the electron donor material perform better than the cells prepared using the zigzag naphtho[1,2‐b:5,6‐b′]dithiophene‐based copolymer. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 305–312