Archaeabacteria bipolar lipid analogues: structure, synthesis and lyotropic properties

Over the past several years, various archaeal symmetrical/unsymmetrical and acyclic/macrocyclic bipolar lipid analogues have been synthesized to study, from well-defined molecules, the membrane organizing and packing properties of this new class of amphiphiles. This review focuses on the structure and the synthesis of selected bolaamphiphiles and describes their supramolecular self-assembling properties in aqueous media.     

Switchable Solubility of Azobenzene-Based Bolaamphiphiles

The ability to design amphiphiles with predictable solubility properties is of everlasting interest in supramolecular chemistry. Relevant structural parameters include the hydrophobic–hydrophilic balance and structural flexibility. In this work, we investigate the water solubility of azobenzene-based triglycerol bolaamphiphiles (TGBAs). In particular, we analyzed the structural effects of backbone hydrophobicity, flexibility, and cis/trans isomerization on the water solubility of a subset of five TGBAs. This leads to the first example of a non-ionic bolaamphiphile whose water solubility can be changed by irradiation with light. The underlying kinetics were monitored using liquid chromatography and a closer analysis of the underlying aggregation processes provides a mechanistic understanding of the light-driven dissolution process. We anticipate that the results obtained will help to engineer bolaamphiphiles with predictable solution properties in the future.     

Bolaamphiphiles promote phospholipid translocation across vesicle membranes

A series of membrane-spanning bolaamphiphiles (molecules with two hydrophilic end groups connected by a hydrophobic linker) were prepared by a modular synthetic method and evaluated for their abilities to affect the dynamics of a surrounding bilayer membrane. The goal was to determine if the bolaamphiphiles promote the translocation of phospholipids across vesicle membranes. The bolaamphiphiles were incorporated at low levels (up to 5 mol %) in vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Inward translocation assays were performed using fluorescent, NBD-labeled phospholipid probes with phosphocholine (PC) or phosphoglycerol (PG) headgroups. The membrane-spanning bolaamphiphiles promote the translocation of both phospholipid probes in the order PG > PC, whereas shorter bolaamphiphiles (structures that must adopt a U-shape and keep both end groups in the same leaflet of the membrane), and regular amphiphiles with one hydrophilic end group, are inactive. These results are an exception to the rule-of-thumb that membrane-spanning bolaamphiphiles are inherently membrane-stabilizing molecules that inhibit all types of membrane transport.     

Formation and characterization of simple and mixed vesicles based on monomeric and oligomeric phosphate bipolar amphiphiles

Certain phosphate bipolar amphiphiles, both monomeric ( I and II ) and polymeric or rather oligomeric (poly- I and poly- II ), were used as basic materials for the preparation of simple and mixed vesicles. Specifically, it was found that oligomeric phosphate bipolar amphiphiles form stable vesicles in aqueous media. The same oligomeric bolaamphiphiles in mixture with their monomeric counterparts also form stable mixed vesicles with sonication; they are relatively less stable with the “thin film method.” Furthermore, it was shown that the method of spanning the membrane of didodecylphosphate vesicels with the dipolar amphiphile II is not effective for enhancing stability. © 1995 John Wiley & Sons, Inc.     

Hexayne Amphiphiles and Bolaamphiphiles

Oligoynes with two or more conjugated carbon–carbon triple bonds are useful precursors for carbon-rich nanomaterials. However, their range of applications has so far been severely limited by the challenging syntheses, particularly in the case of oligoynes with functional groups. Here, we report a universal synthetic approach towards both symmetric and unsymmetric, functionalized hexaynes through the use of a modified Eglinton–Galbraith coupling and a sacrificial building block. We demonstrate the versatility of this approach by preparing hexaynes functionalized with phosphonic acid, carboxylic acid, ammonium, or thiol head groups, which serve as neutral, cationogenic, or anionogenic interfacially active groups. We show that these hexaynes are carbon-rich amphiphiles or bolaamphiphiles that self-assemble at liquid–liquid interfaces, on solid surfaces, as well as in aqueous media.     

Supramolecular assemblies from single-chain hydrocarbon fluorocarbon hybrid bolaamphiphiles

Three types of single-chain hydrocarbon fluorocarbon hybrid bolaamphiphiles were synthesized.They readily formed different kinds of organized supramolecular assemblies,including vesicles,tapes,and micellar fibers,in aqueous solution.The aggregates morphology was characterized by transmission electron microscopy (TEM) after negative staining.The superstructures of these aggregates seemed to be determined by the geometry and the head group's properties of the corresponding amphiphiles.     

Engineered lipids that cross-link the inner and outer leaflets of lipid bilayers

The application of supported lipid bilayer systems as molecular sensors, diagnostic devices, and medical implants is limited by their lack of stability. In an effort to enhance the stability of supported lipid bilayers, three pairs of phosphatidylcholine lipids were designed to cross-link at the termini of their 2-position acyl chain upon the formation of lipid bilayers. The cross-linked lipids span the lipid bilayer, resembling naturally occurring bolaamphiphiles that stabilize archaebacterial membranes against high temperatures. The three reactions investigated here include the acyl chain cross-linking between thiol and bromine groups, thiol and acryloyl groups, and cyclopentadiene and acryloyl groups. All three reactive lipid pairs were found to cross-link in liposomal membranes, as determined by thin-layer chromatography, ion-spray mass spectrometry, and 1H NMR. The monolayer film properties of the reactive amphiphiles were characterized by surface pressure-area isotherms and showed that stable monolayers formed at the air-water interface with limiting molecular areas comparable to that of pure saturated phosphatidylcholine lipids. Langmuir-Blodgett bilayers of dimyristoylphosphatidylcholine incorporating 15 mol % of the reactive thiol and acryloyl lipids had diffusion coefficients comparable with pure dimyristoylphosphatidylcholine, while bilayers with more than 25 mol % of the reactive lipids were immobile, suggesting that interleaflet cross-linking of the lipids inhibited membrane diffusion. Our results show that the reactive lipids can cross-link within a lipid bilayer and are suitable for assembling supported lipid bilayers using Langmuir-Blodgett deposition. By using terminally reactive amphiphiles to build up supported lipid bilayers with cross-linked leaflets, bolaamphiphiles can be incorporated into asymmetric solid supported membranes to increase their stability in biosensor and medical implant applications.     

A family of hydrogels based on ureido-linked aminopolyol-derived amphiphiles and bolaamphiphiles: synthesis, gelation under thermal and sonochemical stimuli, and mesomorphic characterization

This article describes the systematic preparation of a novel family of carbohydrate amphiphiles and bolaamphiphiles in which hydrophilic and hydrophobic units are connected via a ureido or bis(ureido) moiety. The sugar core is derived from aminopolyols such as D-glucamine (1), N-methyl-D-glucamine (2), or the sugar-like species tris(hydroxymethyl)aminomethane (3). The O-unprotected derivatives behave as self-organizing nonionic surfactants with good water gelation ability, which can be induced under thermal or ultrasound-driven stimuli. In addition, some derivatives of 1 and 2, and rarely 3 also formed lyotropic liquid crystals with lamellar or hexagonal structures that exhibit low-temperature transitions.     

Evidence for a reverse U-shaped conformation of single-chain bolaamphiphiles at the air-water interface

Infrared reflection absorption spectroscopy and X-ray reflectivity have been used to elucidate the molecular orientation and hydrocarbon chain conformation and packing of the symmetric long-chain bolaamphiphiles dotriacontane-1,1'-diyl-bis-[2-(trimethylammonio)ethylphosphate] (PC-C32-PC) and dotriacontane-1,1'-diyl-bis-[2-(dimethylammonio)ethylphosphate] (Me2PE-C32-Me2PE) at the air-water interface. At low surface pressures, these bipolar amphiphiles are found to lie flat on the water surface with a disordered chain. With increasing surface pressure, the alkyl chain becomes more ordered. Concomitantly, the chain is bent pointing into the air, whereas both polar headgroups keep contact with the water subphase. At an area of 0.9-1.1 nm2 per molecule, a surface pressure plateau is reached for both bolaamphiphiles, where the molecules adopt a reverse U-shaped conformation with a strongly tilted alkyl chain. Further compression leads to the formation of 3-D aggregates.     

Photophysical and self‐assembly behavior of poly(amidoamine) dendrons with chromophore as scaffold: The effect of dendritic architecture

Two series of amphiphiles composed of hydrophilic poly(amidoamine) dendrons (from the first to the third generation) as the shell and hydrophobic aromatic chromophores (3,6‐di(maleimidyl)‐9‐phenyl carbazole and 9‐(4′‐maleimidyl phenyl)‐3‐maleimidyl carbazole) as the central scaffold were synthesized. The effect of dendritic architecture on the photophysical properties and the self‐assembly behavior of these amphiphiles were studied by UV–vis absorption spectroscopy, fluorescence spectroscopy, and transmission electron microscopy (TEM) measurements. Both the generation of dendritic shell and the location of dendrons at the chromophoric scaffold had great effect on the photophysical properties of these amphiphiles. In addition, different spherical aggregates were formed from these amphiphiles in the aqueous solution at different concentrations. Because of the combined effects of steric hindrance and architecture of dendritic shells, the amphiphiles from G2 dendron with central chromophore self‐organized into ordered aggregates more readily than that from G1 and G3. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4584–4593, 2008     

双头基两亲分子研究进展

本文介绍了双头基两亲分子的结构特征与性质, 概述了由双头基两亲分子在气液界面形成的单分子膜以及在体相中形成的囊泡的特征, 并介绍了这类两亲分子在催化、生物矿化、药物缓释、膜破解以及纳米材料等方面的应用研究。对其研究前景进行了展望。     

Control of surface forces through hydrated boundary layers

Hydration layers surrounding charges or zwitterionic moieties have long been known to play important roles in areas including antifouling and colloidal stability, and particularly over the past 15 years or so, their role in boundary lubrication has been widely investigated. Hydration repulsion because of hydrated ions or polar groups present on surfaces may dominate their interactions at high electrolyte concentrations, so that Derjaguin–Landau–Verwey–Overbeek theory does not apply. Hydration shells, strongly held by the charges they surround, can sustain large pressures without being squeezed out, while by rapidly relaxing, and they behave like a fluid during shear; this may lead to their acting as lubrication vectors with outstanding friction–reduction properties. This review considers hydration layers around trapped ions, polymer brushes, and amphiphiles (surfactants and phosphatidylcholines), focusing on their lubrication properties. Finally, we suggest some prospects for further development of current hydrated vectors and designing new hydrated vectors for modifying surface interactions.     

Facile Synthesis and Photophysical Properties of Sphere–Square Shape Amphiphiles Based on Porphyrin–[60]Fullerene Conjugates

Molecules constructed from a combination of zero‐dimensional ([60]fullerene (C₆₀)) and two‐dimensional (porphyrin (Por)) nanobuilding blocks represent an intriguing category of sphere–square “shape amphiphiles”. These sphere–square shape amphiphiles possess interesting optoelectronic properties. To efficiently synthesize a large variety of C₆₀–Por shape amphiphiles, a facile route based on Steglich esterification was developed. The synthetic strategy enables the preparation of hydroxy‐functionalized Por precursors ( 9 , 10 , 11 , 12 ) with high purity in a one‐pot procedure. All of the C₆₀–Por shape amphiphiles ( 1 , 2 , 3 , 4 , 5 ) can be readily synthesized in good yields through subsequent Steglich esterification with a highly soluble carboxylic acid derivative of methanofullerene ( 13 ). Photophysical studies indicated weak electronic coupling between the C₆₀ and Por moieties and suggest an edge‐to‐face alignment for the moieties. The fluorescence of electronically excited Por portions of each amphiphile was efficiently quenched, which was indicative of electron transfer from ¹Por to the C₆₀ group(s). Increasing the number of C₆₀ groups on the shape amphiphiles led to more pronounced quenching of the Por fluorescence, which indicated the potential for more effective generation of charge‐separated species, C₆₀^?.Por^+., from the photoexcited C₆₀–Por shape amphiphiles.     

Hierarchical self-assembly of bolaamphiphiles with a hybrid spacer and L-glutamic acid headgroup: pH- and surface-triggered hydrogels, vesicles, nanofibers, and nanotubes

Bolaamphiphiles with L-glutamic acid headgroups and hybrid linkers, each composed of two rigid benzene rings and different polymethylene units, were designed, and morphological controls of the hierarchical self-assemblies were realized via changing solution pH and application to solid surfaces. At a low pH of 3, bolaamphiphiles formed hydrogels with water and molecules with short and long spacers formed nanofibers and helical nanoribbon-nanotubes, respectively. In a pH 12 aqueous solution, vesicles were observed from cryo-TEM measurements for amphiphiles with short spacers that could transfer to huge vesicles when cast onto a mica surface. Amphiphiles with longer spacers self-assembled into nanoparticles in a pH 12 aqueous solution while micellar fibers were formed on a mica surface. Those assemblies were characterized with UV-vis, CD, and FT-IR spectroscopy and AFM and TEM observations. With molecular structure modification and the fine tuning of conditions, morphology transitions between various nanostructures were obtained from the self-assembled bolaamphiphiles. The environmental pH can induce different interaction modes between the headgroups, and at high pH, there are strong interactions between molecular assemblies and the mica surface. It is suggested that the active headgroups, rigid necks, and flexible linkers with different lengths render molecules with diverse aggregation morphologies.     

d-xylose-based bolaamphiphiles: Synthesis and influence of the spacer nature on their interfacial and membrane properties

A two-step synthesis, with good yields, of d-xylose-based bolaamphiphiles is described. The monolayer properties, the adsorption behavior and membrane destabilization properties of two bolaamphiphiles differing by their spacers (presence or absence of one double bond) were studied. The presence of one unsaturation has no influence on the interfacial organization at low compression but impairs the stability of the monolayer at high compression. Saturated and unsaturated molecules are suggested to adopt a loop structure at the interface at low compression. The higher degree of freedom of the saturated hydrophobic spacer does not affect the initial diffusion step of the bolaform from the subphase to the interface but greatly slows the arrangement step at the interface. However, once at the interface, their surface-active properties are similar. The higher flexibility of the saturated analogue spacer also greatly increases its lipid vesicle destabilizing property. Its rearrangement within the lipid bilayer is in favour of the formation of inverted phases, facilitating membrane fusion.     

Self-organization of double-chained and pseudodouble-chained surfactants: counterion and geometry effects

Self-organization in aqueous systems based on ionic surfactants, and their mixtures, can be broadly understood by a balance between the packing properties of the surfactants and double-layer electrostatic interactions. While the equilibrium properties of micellar systems have been extensively studied and are understood, those of bilayer systems are less well characterized. Double-chained and pseudodouble-chained (or catanionic) surfactants are among the amphiphiles which typically form bilayer structures, such as lamellar liquid–crystalline phases and vesicles. In the past 10–15 years, an experimental effort has been made to get deeper insight into their aggregation patterns. With the double-chained amphiphiles, by changing counterion, adding salt or adding anionic surfactant, there are possibilities to depart from the bilayer aggregate in a controlled manner. This is demonstrated by several studies on the didodecyldimethylammonium bromide surfactant. Mixtures of cationic and anionic surfactants yield the catanionics, surfactants of the swelling type, and also show a rich phase behavior per se. A variety of liquid–crystalline phases and, in dilute regimes, equilibrium vesicles and different micellar shapes are often encountered. Phase diagrams and detailed structural studies, based on several techniques (NMR, microscopy and scattering methods), have been reported, as well as theoretical studies. The main features and conclusions emerging from such investigations are presented.     

Facial amphiphiles in molecular recognition: From unusual aggregates to solvophobically driven foldamers

The term “facial amphiphiles” was originally used for molecules with the hydrophilic and hydrophobic groups located on two opposite faces, rather than at two ends as in the more conventional head/tail amphiphiles. Recent research has expanded this concept and created facially amphiphilic molecules with diverse topologies and intriguing properties. The geometry and the distribution of hydrophilic/hydrophobic groups on facial amphiphiles were key parameters influencing their properties. Intermolecular aggregation of facial amphiphiles generated a range of structures including dimers, vesicles, nanoclusters, and nanotubes. Intramolecular aggregation of facially amphiphilic repeat units in a molecule, on the other hand, allowed the molecule to respond to environmental stimuli through controlled conformational changes.     

Pristine Carbon‐Nanotube‐Included Supramolecular Hydrogels with Tunable Viscoelastic Properties

Research investigations involving pristine carbon nanotubes (CNTs) and their applications in diversified fields have been gathering enormous impetus in recent times. One such emerging domain deals with the hybridization of CNTs within hydrogels to form soft nanocomposites with superior properties. However, till now, reports on the inclusion of pristine CNTs within low‐molecular‐weight hydrogels are very scarce due to their intrinsic feature of remaining in the bundled state and strong repulsive behavior to the aqueous milieu. Herein, the synthesis of a series of amino acid/dipeptide‐based amphiphilic hydrogelators having a quaternary ammonium/imidazolium moiety at the polar head and a C16 hydrocarbon chain as the hydrophobic segment is reported. The synthesized amphiphiles exhibited excellent hydrogelation (minimum gelation concentration (MGC) ≈0.7–5 % w/v) as well as single‐walled carbon nanotube (SWNT) dispersion ability in aqueous medium. Interestingly, the dispersed SWNTs were incorporated into the supramolecular hydrogel formed by amphiphiles with an imidazolium moiety at the polar end through complementary cation–π and π–π interactions. More importantly, the newly synthesized hydrogelators were able to accommodate a significantly high amount of pristine SWNTs (2–3.5 % w/v) at their MGCs without affecting the gelating properties. This is the first time that such a huge amount of SWNTs has been successfully incorporated within hydrogels. The efficient inclusion of SWNTs to develop soft nanocomposites was thoroughly investigated by spectroscopic and microscopic methods. Remarkably, the developed nanocomposites showed manifold enhancement (≈85‐fold) in their mechanical strength compared with native hydrogel without SWNTs. The viscoelastic properties of these nanocomposites were readily tuned by varying the amount of incorporated CNTs.     

Routes to Functional Vesicle Membranes without Proteins

Fixation of reaction partners at appropriate distances from one another is a structural prerequisite for vectorial reactions and reaction sequences. In biological systems (e.g. the photosynthetically active thylakoid membrane or membrane receptors) the positions of the reaction centers are fixed by membrane-protein complexes, but little is known about the structure of these complexes. Ordered reactive systems in synthetic vesicle membranes were first obtained by employing amphiphiles with reactive head groups as building units, by regioselective incorporation of foreign molecules into the membrane, by alignment of bolaamphiphiles with two head groups of differing solubility or size, and by the formation of domains. Chiral superstructures have also been observed in membranes, and the first stereoselective reactions have been performed in vesicle membranes. The report concludes with a brief discussion of membranes constructed from non-amphiphilic building blocks and problems which still have to be solved.     

Axially Chiral Facial Amphiphiles with a Dihydronaphthopentaphene Structure as Molecular Tweezers for SWNTs

Syntheses of chiral 6,15‐dihydronaphtho[2,3‐c]pentaphene derivatives of opposite configurations are reported. Starting from anthracene, the strategy involves two key steps: a Diels–Alder reaction on a prochiral dianthraquinone, and an enantiomeric resolution using (?)‐menthol. The final molecules exhibit very strong optical activity, as shown by their circular dichroism spectra, and are examples of chiral facial amphiphiles. Their adsorption at the surface of single‐walled carbon nanotubes (SWNTs) has also been studied, and has been found to occur preferentially on 0.8–1.0 nm diameter nanotubes among the population of a high‐pressure CO conversion (HiPco) SWNT sample (0.8–1.2 nm). The synthesised facial amphiphiles act as nano‐tweezers for the diameter‐selective solubilisation of SWNTs in water. The expected optical activities of the SWNT samples solubilised by each of the chiral amphiphiles have been studied by circular dichroism spectroscopy, but the results are not yet conclusive.