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.     

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.     

Synthesis of cationic ether lipids of alkyl type with short-chain substituents at the 2-position of the glycerol backbone

A series of cationic ether lipids with short-chain substituents at the 2-position and various cationic groups attached directly or through a spacer group to the glycerol backbone was synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1826–1830, October, 1994.This work was supported by the Russian Foundation for Basic Research (Project No. 94-03-08-166).     

Synthesis of sulfur-containing cationic lipids of the 1,3-dioxolane type

A series of cationic acetal lipids containing different spacer and cationic groups were synthesized starting from 1,2-O-hexadecylidene-3-thioglycerol. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1590–1592, August, 1998.     

Synthesis of alkyl glycerolipids with various cationic groups linked directly to the glycerol backbone

A number of positively charged lipids containing pyridinium,N-methylmorpholinium,N-methylimidazolinium, 4-N,N-dimethylaminopyridinium, and 4-N,N-dimethylcyclo-hexylammonium groups linked directly to the C(3) atom of 1,2-di-O-alkylglycerols with Br⁻, MsO⁻, and TsO⁻ anions as counterions were synthesized. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1381–1384, July, 1999.     

Synthesis and characterization of a new dimeric polyoxometalate based on Anderson-type polyoxoanions and a trinuclear lanthanide coordination complex

An unusual compound, H₅[(C₆NO₂H₄)₄(H₂O)₁₅Nd₃][IMo₆O₂₄]₂·13.5H₂O (1) has been synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA), and single crystal X-ray diffraction. Compound 1 consists of two [IMo₆O₂₄]^5? units joined by a trinuclear neodymium-pyridine-4-carboxylic acid complex, resulting in a dimeric polyoxometalate, which further interact via weak intermolecular interactions to form a three-dimensional supramolecular framework with channels. To the best of our knowledge, no analogous dimeric polyoxometalate structure composed of an Anderson-type polyoxometalate has been reported in the literature.     

Effect of hydrocarbon structure of the headgroup on the thermodynamic properties of micellization of cationic gemini surfactants: an electrical conductivity study

A series of cationic gemini surfactants butanediyl-1,4-bis(dodecyldialkylammonium bromide), C(12)H(25)N(+)(C(m)H(2)(m)(+1))(2)C(4)H(8)N(+)(C(m)H(2)(m)(+1))(2)C(12)H(25)·2Br(-), where m=1, 2, 3, 4, referred to as C(12)C(4)C(12)(Me), C(12)C(4)C(12)(Et), C(12)C(4)C(12)(Pr), and C(12)C(4)C(12)(Bu), respectively, were synthesized, and their thermodynamic properties of micellization were studied by electrical conductivity measurements. There existed a minimum critical micelle concentration (cmc) in the curve of cmc versus temperature, and the temperature of the minimum of cmc (T(min)) increased with increasing the headgroup alkyl chain length. The values of log (cmc) depended linearly on carbon number of the alkyl chains, but that was not true for the carbon number of the headgroup substituents. The temperature dependence of cmc and degree of counterion association (β) were used to calculate the Gibbs free energy (Δ(mic)G°), enthalpies (Δ(mic)H°) and entropies (Δ(mic)S°) of micelle formation for these gemini surfactants, and well correlated enthalpy-entropy compensation was observed. The analyses showed C(12)C(4)C(12)(Me) and C(12)C(4)C(12)(Et) behaved similarly in terms of thermodynamics of micellization, but they behaved differently from C(12)C(4)C(12)(Pr) and C(12)C(4)C(12)(Bu), which could be ascribed to the hydrophobicity and the location of the headgroup alkyl chains in the aggregates. These initial results indicate the headgroup alkyl chain plays an important role in influencing the thermodynamic properties of gemini surfactants.     

The relationship between ligand structures and their CoII and NiII complexes: Synthesis and characterization of novel dimeric CoII/CoIII complexes of bis(thiosemicarbazone)

4,6-Diacetylresorcinol serves as a starting point for the generation of multidentate S/N/O or O/N/O symmetrical chelating agents by condensation with thiosemicarbazide or semicarbazide to yield the corresponding bis(thiosemicarbazone) H₄L¹ or bis(semicarbazone) H₄L², respectively. Reaction of H₄L¹ and H₄L² with M(NO₃)₂·6H₂O (M?=?Co or Ni) afforded dimeric complexes for H₄L¹ and binuclear complexes for H₄L², revealing the tendency of S to form bridges. The dimeric cobalt complexes of H₄L¹ are very interesting in that they contain Co^II/Co^III, side/side, low-spin octahedral coordinated Co^III-ions and high-spin square-planar coordinated Co^II-ions. These complexes have the general formula [(H₂L¹)₂Co₂(H₂O) (NO₃)]·nEtOH. Arguments supporting these anomalous Co^II/Co^III structures are based on a pronounced decrease in their magnetic moments, elemental and thermal analyses, visible and IR spectra, as well as their unreactivity towards organic bases such as 1,10-phenanthroline (phen), 2,2′-bipyridine (Bpy), N,N,N′,N′-tetramethylethylenediamine (Tmen) and 8-hydroxyquinoline (oxine, Ox). The dimeric octahedral Ni^II complex [(H₂L¹)₂Ni₂(H₂O)₄]·3H₂O showed higher reactivity towards phen and Bpy and formed adducts; [(HL¹)Ni₂(B)(H₂O)₅] NO₃ (B?=?phen or Bpy). In the presence of oxine, the dimeric brown paramagnetic octahedral complex [(H₂L¹)₂Ni₂(H₂O)₄]·3H₂O was transformed to the dimeric brick-red diamagnetic square-planar complex [(H₃L¹)₂Ni₂](NO₃)₂. The latter showed dramatic behavior in its ¹H NMR spectrum in DMSO-d ₆, which was explained on the basis of H⁺-transfer. By contrast, the binuclear Ni^II–H₄L² complex (11) showed higher reactivity towards phen, Bpy and oxine. These reactions afforded mixed dimeric complexes having the molar ratio 2?:?2?:?1 (Ni^II?:?H₄L²?:?base). The binuclear Co^II–H₄L² complex afforded an adduct with phen and trinuclear complexes with Bpy and oxine. All complexes were found to be unreactive towards Tmen. Structural characterization was achieved by elemental and thermal analyses, spectral data (electronic, IR, mass and ¹H NMR spectra) and conductivity and magnetic susceptibility measurements.     

Nanostructure of complexes between cationic lipids and an oppositely charged polyelectrolyte

The morphology of aqueous solutions of polyelectrolytes and oppositely charged lipids is the subject of extensive colloid science research, because of their application in industry and medicine, the latter especially for gene therapy. In this work, we show that complexes of two different cationic lipids with the polyelectrolyte sodium poly(acrylic acid), PAA, share similar morphology with the complexes of those lipids with nucleic acids, implying a broader and universal packing phenomenon. We characterized by direct-imaging cryogenic-temperature transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and zeta (ζ)-potential two cationic lipids, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and bis(11-ferrocenylundecyl) dimethylammonium bromide (BFDMA), which are used in gene transfection, at equivalent lipid/polyelectrolyte charge ratio. Our results revealed that, for both types of complexes, onion-like multilamellar nanostructures formed, which exhibited similar morphology as in complexes of DNA or oligonucleotides (lipoplexes), based on the same lipids. Our findings suggest that the onion-like packing may be energetically favorable for a wide range of polyelectrolyte-liposome systems, from oligonucleotides and DNA to PAA.     

Synthesis of dimeric estradiol enzyme model containing imidazolyl and study on its catalytic efficiency in hydrolysis of carboxylates and phosphates

Dimeric estradiol enzyme model (2) was synthesized by etherification of 2,4-bis(N-imidazolylmethyl)-17β-estradiol (1) with 1,3-dibromopropane in the presence of anhydrous K2CO3. Hydrolysis of carboxylates and phosphates catalyzed by the model showed Michaelis-Menten kinetic behavior. Hydrophobic interaction between the model and ester accelerates the hydrolysis markedly, rate enhancement of up to 65 and 285 fold, relative to imidazole, is observed.     

Water-soluble complexes between cationic surfactants and comb-type copolymers consisting of an anionic backbone and hydrophilic nonionic poly(N,N-dimethylacrylamide) side chains

The formation of complexes between the cationic surfactant dodecyl trimethylammonium bromide (DTAB) and the comb-type anionic polyelectrolytes poly(sodium acrylate-co-sodium 2-acrylamido-2-methylpropane sulfonate)-g-poly(N,N-dimethylacrylamide) (P(NaA-co-NaAMPS)-g-PDMAMx) was investigated in dilute aqueous solutions by means of turbidimetry, pyrene fluorescence probing, viscometry, z-potential measurements, and dynamic light scattering. The comb-type copolymers consist of an anionic copolymer backbone, P(NaA-co-NaAMPS), containing 84 mol % NaAMPS units, while the weight percentage, x, of the PDMAM side chains varies from x = 12% (w:w) up to x = 58% (w:w). It was found that, contrary to the water-insoluble complexes formed between the linear polyelectrolyte P(NaA-co-NaAMPS) and DTAB, the solubility in water of the complexes formed between the comb-type copolymers and DTAB is significantly improved with increasing x. The complexation process starts at the same critical aggregation concentration (about 2 orders of magnitude lower than the critical micelle concentration of DTAB), regardless of x, and it is accompanied by charge neutralization and appearance of hydrophobic microdomains. Both effects lead to the substantial collapse of the polyelectrolyte chain upon addition of DTAB. However, the complexes of the comb-type copolymers with DTAB are stabilized in water as nanoparticles, and probably consisted of a water-insoluble core (the polyelectrolyte/surfactant complex), protected by a hydrophilic nonionic PDMAM corona. The size of the nanoparticles varies from approximately 35 nm up to approximately 120 nm, depending on x.     

Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids

The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC) as positive controls. All cationic lipids (controls and single-chain lipids) were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE). Cationic lipid-siRNA complexes of varying (+/-) molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/-) molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.     

Synthesis,characterization and comparative studies of mono- and dimeric copper(II) complexes containing tripodal ligands

Mono and dimeric bromo-bridged copper(II) complexes of the type [CuBr₂(L)] and [Cu₂Br₂(L)₂](ClO₄)₂ containing nitrogen donor tripodal ligands L = 2,6-bis(pyrazol-1-yl)pyridine (bppy) or 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (dmbppy) have been synthesized. All complexes have been characterized by elemental analysis, IR, ESR and electronic spectra and magnetic susceptibility and cyclic voltammetry measurements.     

Isolation and characterization of an iodide bridged dimeric palladium complex in carbonylation of methanol

Palladium-catalyzed carbonylation of methanol in presence of iodide promoters was investigated. Iodide bridged palladium dimeric complex, [PPh₃CH₃]₂[Pd₂I₆] was isolated from the carbonylation reaction mixture and characterized using X-ray crystallography. Reaction mechanism was proposed based on IR and UV spectroscopic characterizations of catalytic species involved in the catalytic cycle. The isolated dimeric palladium species, [Pd₂I₆]²⁻ underwent carbonylation to give monomeric species [PdI₃CO]⁻ at atmospheric pressure of carbon monoxide. It was also observed that PPh₃ plays an important role to avoid catalyst deactivation at higher temperatures. Turnover frequency (TOF) of 1052 h⁻¹ was achieved using Pd(OAc)₂-HI-PPh₃ catalyst system at 175 °C.     

Synthesis and characterization of graft copolymers based on poly(p-phenylene terephthalamide) backbone and well-defined polystyrene side chains

<正>A novel dualfunctional monomer,2-(2',2',6',6'-tetramethyl-piperidinyl-1'-oxy)methylbenzene-1,4-dioyl chloride hydrochloride,with two acid chloride groups for step-growth polymerization and a nitroxide group for the mediation of living radical polymerization was synthesized.It was first copolymerized with terephthaloyl chloride and p-phenylenediamine at a feed molar ratio of 1:3:4 in N-methyl-2-pyrrolidone containing 10 wt%calcium chloride at -10℃to yield a poly(p-phenylene terephthalamide) based macroinitiator,which initiated radical polymerization of styrene at 125℃to obtain a series of poly(p-phenylene terephthalamide)-g-polystyrenes.A combinatory analysis of proton nuclear magnetic resonance spectroscopy,Fourier transform infrared spectroscopy,elementary analysis,thermogravimetry and gel permeation chromatography indicated that the macroinitiator induced the radical polymerization of styrene to proceed in a well-controlled way.The molecular weight of side-chains increased with an increase of monomer conversion,and the molecular weight distribution index remained lower than 1.5.The graft copolymers showed a remarkably improved solubility in N-methyl -2-pyrrolidone and much depressed crystallinity in bulk.     

A novel fluorine‐containing graft copolymer bearing perfluorocyclobutyl aryl ether‐based backbone and poly(methyl methacrylate) side chains

A series of novel graft copolymers consisting of perfluorocyclobutyl aryl ether‐based backbone and poly(methyl methacrylate) side chains were synthesized by the combination of thermal [2π + 2π] step‐growth cycloaddition polymerization of aryl bistrifluorovinyl ether monomer and atom transfer radical polymerization (ATRP) of methyl methacrylate. A new aryl bistrifluorovinyl ether monomer, 2‐methyl‐1,4‐bistrifluorovinyloxybenzene, was first synthesized in two steps from commercially available reagents, and this monomer was homopolymerized in diphenyl ether to provide the corresponding perfluorocyclobutyl aryl ether‐based homopolymer with methoxyl end groups. The fluoropolymer was then converted to ATRP macroinitiator by the monobromination of the pendant methyls with N‐bromosuccinimide and benzoyl peroxide. The grafting‐from strategy was finally used to obtain the novel poly(2‐methyl‐1,4‐bistrifluorovinyloxybenzene)‐g‐poly(methyl methacrylate) graft copolymers with relatively narrow molecular weight distributions (M_w/M_n ≤ 1.46) via ATRP of methyl methacrylate at 50 °C in anisole initiated by the Br‐containing macroinitiator using CuBr/dHbpy as catalytic system. These fluorine‐containing graft copolymers can dissolve in most organic solvents. This is the first example of the graft copolymer possessing perfluorocyclobutyl aryl ether‐based backbone. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and characterization of aromatic polyazomethines bearing pendant pentadecyl chains

Aromatic diamine monomer viz., 4-(4′-aminophenoxy)-2-pentadecylbenzenamine containing pendant pentadecyl chain was synthesized starting from cashew nut shell liquid - a renewable resource material and was characterized by FTIR, ¹H and ¹³C NMR spectroscopy. A series of new (co) polyazomethines containing pendant pentadecyl chains and flexibilizing ether linkages was synthesized by polycondensation of 4-(4′-aminophenoxy)-2-pentadecyl benzenamine with commercially available aromatic dialdehydes viz., terephthaldehyde (TPA), isophthaldehyde (IPA) and varying mixture of TPA and IPA. Inherent viscosities and number average molecular weights of (co) polyazomethines were in the range 0.50-0.70 dL/g and 10,490-40-800 (GPC, polystyrene standard), respectively indicating formation of medium to reasonably high molecular weight polymers. (Co) polyazomethines containing pendant pentadecyl chains were found to be soluble in common organic solvents such as chloroform, dichloromethane, tetrahydrofuran, pyridine, m-cresol and could be cast into transparent and stretchable films from their solution in chloroform. (Co) polyazomethines were essentially amorphous in nature and the formation of loosely-developed layered structure was observed arising from the packing of pendant pentadecyl chains. Polyazomethines exhibited glass transition temperatures (T_g) in the range 21-48 °C. The observed depression of glass transition temperature could be ascribed to the “internal plasticization” effect of pentadecyl chains. The temperature at 10% wt loss (T₁₀), determined from TGA in nitrogen atmosphere of polyazomethines were in the range 434-441 °C indicating their good thermal stability.