Unsymmetrical Bolaamphiphiles Research Articles

Retraction of "Self-Assembly and Thermal Phase Transition Behavior of Unsymmetrical Bolaamphiphiles Having Glucose- and Amino-Hydrophilic Headgroups".

Retraction of "Self-Assembly and Thermal Phase Transition Behavior of Unsymmetrical Bolaamphiphiles Having Glucose- and Amino-Hydrophilic Headgroups".

Synthesis of symmetrical, single-chain, phenylene/biphenylene-modified bolaamphiphiles

Two new, symmetrical, phenylene- or biphenylene-modified bolaamphiphiles bearing two phosphocholine headgroups and an alkyl spacer chain length of 32 and 36 carbon atoms, respectively, have been synthesised. The key step was the Cu(II)-catalysed Grignard reaction used either as a simultaneous bis-coupling procedure or in a stepwise homo-coupling. Particularly with the use of the homo-coupling, we were able to separate the phenylene-free by-products from the desired products. This homo-coupling additionally offered the possibility of preparing unsymmetrical bolaamphiphiles. Conversion of the diols into bipolar phospholipids was achieved by bis-phosphorylation with β-bromoethylphosphoric acid dichloride and subsequent quarternisation with trimethylamine. Unlike previous studies with aliphatic bolaamphiphiles that formed flexible nanofibres in aqueous suspension, the bolaamphiphiles of the present study, containing phenylene- and biphenylene groups in the middle part of the alkyl spacer chain, formed small ellipsoidal aggregates at ambient temperature.

Lactose-ornithine bolaamphiphiles for efficient gene delivery in vitro

The development of new nonviral vectors characterized by high transfection efficiency and low cytotoxicity remains an important challenge in the field of gene delivery. Unsymmetrical bolaamphiphiles (bolas) appear as new emerging candidates for this application. In this work, new unsymmetrical bolas, bearing neutral lactonic acid and cationic ornithine residues at the two ends of a hydrophobic spacer, were synthesized and their properties were compared to analogues bearing a gluconic acid residue. The new bolas showed DNA binding and condensation at higher N/P ratios than their gluconic analogues, probably due to their larger neutral head group. Whereas the size of the complexes of the new bolas with DNA (bolaplexes) increased with N/P, as a result of charge neutralization, their formulations with DOPE at high N/P were of small size (ca. 200nm). These DOPE formulations showed high transfection efficiency in different cell lines (HeLa, COS-7 and HepG2), close to that of jetPEI. Their cytotoxicity was relatively low, which allowed repetitive transfection in vitro. Fluorescence imaging showed that the bolaplexes bind rapidly to cell surface and internalize mainly through endocytosis. This work suggests a new type of efficient nonviral vectors based on bolaamphiphiles.

New Unsymmetrical Bolaamphiphiles: Synthesis, Assembly with DNA, and Application for Gene Delivery

The success in gene therapy relies strongly on new efficient gene delivery vectors. Nonviral vectors based on lipids and polymers constitute an important alternative to the viral vectors. However, the key problem with these vectors is the poor structural control of their DNA complexes. In the present work, following new design we synthesized unsymmetrical bolaamphiphiles, molecules bearing neutral sugar (gluconic acid) and dicationic ornithine head groups connected by different long hydrophobic spacers. Within this design, a positively charged headgroup is expected to bind DNA, the hydrophobic spacer is to drive the formation of a monolayer membrane shell around DNA, while the neutral group is to be exposed outside of the complex. Our fluorescence and gel electrophoresis data showed that self-assembly of bolas and their interaction with DNA depend strongly on the bola structure. The size of bola/DNA complexes (bolaplexes) estimated from dynamic light scattering data was ∼100 nm at low N/P (cationic nitrogen/DNA phosphate molar ratio), while at higher N/Ps it was significantly larger due to neutralization of their surface charge. Atomic force microscopy studies revealed nanostructural rod-shaped or spherical morphology of the bolaplexes. Transfection efficiency of the bolaplexes in vitro was significant when either DOPE or chloroquine were used as helping agents, suggesting that the key barrier for their internalization is the endosomal escape. Finally, all bolas showed low cytotoxicity (cell viability >80%). The present results show that bolas are prospective candidates for construction of nonviral gene delivery vectors. We believe that further optimization of polar head groups and a hydrophobic spacer in the bolas will lead to vectors with controlled small size and high transfection efficiency.

Self‐Assembled Structures of Catanionic Associations: How to Optimize Vesicle Formation?

AbstractLike other amphiphilic compounds, bolaforms do not always possess surfactant properties; it depends on the spacer chain length and the nature of the polar head group (both sufficiently hydrophobic or hydrophilic, respectively, to intensify the amphiphilic properties). In this regard, unsymmetrical bolaamphiphiles bearing a sugar polar head group and a carboxylic acid function at the opposite ends of a hydrophobic binding spacer were synthesized. These biocompatible sugar‐derived bolaforms were associated with basic fatty amines, by an acid–base reaction, to obtain catanionic mixtures. Associations with 1,7‐lactobionamidoheptanoic acid and decylamine or octylamine spontaneously form stable 200–600 nm vesicles. This new type of association may find an application in drug delivery since catanionic vesicles can transport active substances inside the hydrophilic core, as well as hydrophobic drugs within the bilayer.

Unprecedented parallel packing of unsymmetrical bolaamphiphiles driven by π–π stacking of cinnamoyl groups

The self-assembly and molecular packing mode of a novel, unsymmetrical bolaamphiphile, sodium 4-(6-hydroxyhexyloxy) cinnamate (SHHC) was studied. Tube-like structures were obtained in SHHC aqueous solution at pH 9.2. Upon UV irradiation, the SHHC molecules in the system were found to undergo four-center-type photocyclodimerization and photoisomerization. The combination of IR, XRD and Zeta potential results suggested the formation of a tail-to-tail type bilayer membrane structure: the SHHC molecules stretched upright with the cinnamate headgroups toward the outside in each layer, whereas the tail OH groups of two layers remained inside and formed interlayer hydrogen bonds. This parallel packing mode of SHHC molecules in the membrane was also confirmed by the pH-induced self-assembly transition. With increasing pH from 9.2 to 12.0, the low-curvatured tubes transformed into spherical vesicles, which was in line with the increased outer leaflet head group area as increasing pH. Our results demonstrated that upon careful molecular design, the orientation of unsymmetrical bolaamphiphiles can be controlled; π–π interactions between cinnamoyl groups were found to be strong enough to drive the formation of well-oriented molecular assemblies.

Synthesis of unsymmetrical saturated or diacetylenic cationic bolaamphiphiles

This work presents the synthesis of novel unsymmetrical bolaamphiphiles bearing a sugar residue and a cationic glycine betaine moiety connected to both ends of a C 22 or C 32 oligomethylene bridging chain possessing or not a diacetylenic unit. Preliminary transmission electron microscopy (TEM) studies revealed the polymorphism of these bola lipids with regard to their self-assembled morphologies in water depending on the presence or not of the diacetylenic functionality and on alkyl chain length.

Interfacial Tension of Unsymmetrical Bolaamphiphile Surfactant in Surfactant/Alkali/Crude Oil Systems

The dynamic interfacial tensions between crude oil from Liaoning Daqing Oil Field of China and solution of unsymmetrical bolaamphiphile surfactants were measured. It was found that the added surfactants are greatly effective in reducing the interfacial tensions and can reduce the tensions of oil/water interface to ultra-low (under 10−2 mN/m) at the low surfactant concentration. Otherwise, different aromatic rings attached in the surfactant molecule play an important role on the surfactant capability in reducing crude oil/water interface. The results show that the surfactants with the larger aromatic ring can obtain the lower interfacial tension for their strong adsorption at crude oil/water interface, which provides further examination of this kind of surfactant in reducing crude oil/water interface.

Effect of Ionic Strength on the Interfacial and Bulk Properties of Unsymmetrical Bolaamphiphiles

AbstractBy performing measurements of the equilibrium surface tensions of electrolyte solutions of three unsymmetrical bolaamphiphiles, each of which has an aromatic ring and a ω‐carboxyalkyl chain in its molecular structure, we conclude that the carboxyl and sulfonate groups at both ends of the molecule—which enter the solution while the hydrophobic chain extends into the air—can force these surfactants to adopt a looped configuration which looks like the letter “U” upside‐down, resulting in regular arrangements at the air/water interface and micelles in bulk solution. Surface tension measurements of these surfactants as a function of added salt reveal the limiting surface tension to be less sensitive to the ionic strength in LiCl solution and significantly sensitive to divalent Ca2+ and Mg2+ ions in hard water. This result reveals that the looped configuration of the molecule is the dominant factor in determining whether the molecules of this surfactant are sensitive to ionic strength or not. This paper also reports briefly on the effect of the interactions of divalent Ca2+ and Mg2+ ions with unsymmetrical bolaamphiphiles on the turbidity of hard water. These results suggest that the interactions of divalent Ca2+ and Mg2+ ions with carboxyl groups are strong, and the two breaks in the surface tension curves disappear. In 200 ppm hard water, the turbidity appears over just a small range of surfactant concentrations, showing that the presence of the Ca2+ and Mg2+ ions has little effect on the application of these surfactants.

Molecular Monolayer Nanotubes Having 7–9 nm Inner Diameters Covered with Different Inner and Outer Surfaces

Abstract Novel unsymmetrical bolaamphiphile, bearing glucose- and triglycine-headgroups at both ends, exclusively self-assembled into nanotubes with 7–9-nm inner diameters, which consist of a single monolayer lined by polyglycine-II-type hydrogen-bond networks among the triglycine moieties.

Functionalizable Organic Nanochannels Based on Lipid Nanotubes: Encapsulation and Nanofluidic Behavior of Biomacromolecules

The amino groups on the inner surface of the nanotube that was self-assembled from unsymmetrical bolaamphiphile, N-(2-aminoethyl)-N‘-(β-d-glucopyranosyl)-icosanediamide 1, were modified covalently with a fluorescence donor dye. This functionalization of the nanotube inner surfaces has allowed us to achieve the construction of an optical recognition system for the encapsulation of guest molecules. Fluorescence resonance energy transfer (FRET) from the fluorescence donor located on the inner surface to the ferritin labeled with fluorescence acceptor enabled us to visualize the encapsulation and nanofluidic features of the ferritin in the nanochannel shaped by the hollow cylinder structure. By using this system, we were able to estimate the diffusion constants for ferritin and gold nanoparticles in the organic nanochannels on the basis of lipid nanotubes. We have also demonstrated that the size and surface charge of the nanochannel strongly affect the encapsulation behavior toward the biomacromolecules such ...

Self-assembly and thermal phase transition behavior of unsymmetrical bolaamphiphiles having glucose- and amino-hydrophilic headgroups.

The thermal phase transition and self-assembly behaviors in water of the crystalline lamellar films prepared from unsymmetrical bolaamphiphiles, N-(2-aminoethyl)-N'-(beta-d-glucopyranosyl)-alkanediamide [1(n), n = 12, 14, 16, 17, 18, and 20], have been studied using differential scanning calorimetry, polarized light microscopy, variable-temperature (VT) X-ray diffraction (XRD), and VT-IR spectroscopy. The behavior allowed us to classify the bolaamphiphiles into two categories: short chain 1(n) (n = 12, 14, 16, and 17) and long chain 1(n) (n = 18 and 20). On heating, the films of the long chain 1(n) exhibited polymorphism of two crystal phases (Cr1 and Cr2) and one thermotropic mesophase (smectic). These phases proved to consist of unsymmetrical monolayer lipid membranes (MLMs), in which the molecules packed in a parallel fashion. On the other hand, the films of the short chain 1(n) gave a single crystal phase (Cr1) consisting of symmetrical MLMs with antiparallel molecular packing. Scanning transmission electron microscopy and atomic force microscopy revealed that the long chain 1(n) self-assembles in alkaline aqueous solutions to form nanotubes with 110-120 nm outer diameters, while the short chain 1(n) produces nanotapes with 80-250 nm widths. XRD and IR measurements revealed that the nanotubes consist of unsymmetrical MLMs, while the nanotapes consist of symmetrical MLMs. The molecular packing of the initial solid phase was essentially maintained even in the self-assemblies in water. The self-assembly process in water allowed the symmetrical MLM films of the short chain 1(n) to convert into the symmetrical MLM nanotapes. Similarly, the unsymmetrical MLM films of the long chain 1(n) were converted into the unsymmetrical MLM nanotubes.

Self‐assembled lipid nanotube hosts: The dimension control for encapsulation of nanometer‐scale guest substances

AbstractSupramolecular nanotube hosts with precisely controlled inner or outer diameters have been synthesized by self‐assembly of unsymmetrical bolaamphiphilic monomers or glucopyranosylamide lipids, respectively. Time‐resolved fluorescent measurement using 8‐anilinonaphthalene‐1‐sulfonate (ANS) as a probe revealed that the water confined in a cardanyl‐β‐D‐glucopyranoside lipid nanotube has relatively lower solvent polarity corresponding to that of propanol than bulk water. Extensively developed hydrogen bond networks also characterize the confined water in comparison to the case in bulk water. Encapsulation ability of the glucopyranosylamide lipid nanotube has been examined by filling the lyophilized LNTs with gold or silver nanoparticles, ferritin, or magnetic crystals. Filling the unsymmetrical bolaamphiphile nanotube possessing positively charged inner surfaces with negatively charged polymer beads or ferritin proved to be successful without depending on capillary action. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5137–5152, 2006

Supramolecular Nanotube Hosts for Encapsulation of 10-nm-Scale Objects

AbstractSupramolecular nanotube hosts with precisely controlled inner or outer diameters have been synthesized by self-assembly of cardanol-based glycolipids, glucopyranosylamide lipids, or glucose-based unsymmetrical bolaamphiphiles. Time-resolved fluorescent measurement using 8-anilinonaphtahalene-1-sulfonate (ANS) as a probe revealed that the water confined in a cardanol-based glycolipid nanotube has relatively lower solvent polarity than bulk water, which corresponds to that of 1-propanol. Extensively developed hydrogen bond networks also characterize the confined water in comparison to the case in bulk water. Encapsulation ability of the glucopyranosylamide lipid nanotube, which depends on capillary action, has been examined by filling the lyophilized lipid nanotubes with aqueous dispersions of gold or silver nanocrystals, ferritin, or magnetic crystals. We have also succeeded in filling the unsymmetrical bolaamphiphile nanotube, which possesses positively charged inner surfaces, with negatively charged polymer beads or ferritin without depending on capillary action.

Inside Front Cover: Selective Construction of Supramolecular Nanotube Hosts with Cationic Inner Surfaces (Adv. Mater. 22/2005)

AbstractSelective construction of a supramolecular nanotube host with a cationic inner surface consisting of unsymmetrical bolaamphiphiles is reported on p. 2732 by Masuda, Shimizu, and co‐workers. The nanotube, shown schematically on the inside cover, has different inner and outer surfaces covered with amino and sugar functionalities, respectively, and is able to effectively encapsulate anionic nanomaterials, such as sulfate‐latex beads (see TEM image) and spherical proteins, in the cationic hollow cylinder without depending on capillary action.

Polymorphism of monolayer lipid membrane structures made from unsymmetrical bolaamphiphiles

The crystal structures of synthetic unsymmetrical 1-glucosamide- and 1-galactosamide bolaamphiphiles, 13-[(β- d-glucopyranosyl)carbamoyl]tridecanoic acid ( 1) and 15-[(β- d-galactopyranosyl)carbamoyl]pentadecanoic acid ( 2), respectively, were elucidated by single-crystal X-ray analysis. The space group for 1 is P2 1, Z = 2 with cell dimensions: a = 8.6816(9), b = 4.8578(5), c = 26.250(3) Å, β = 91.460(2)°; that for 2 P2 1, Z = 2 with cell dimensions: a = 4.90(1), b = 40.139(1), 6.289(1) Å, β = 106.48(1)°. The glucopyranosyl and galactopyranosyl rings in 1 and 2, respectively, take a 4 C 1 chair conformation. In the crystal lattice, the 1-glucosamide 1 forms a symmetrical monolayer lipid membrane (MLM) structure in which the molecules are packed in an antiparallel fashion, while 1-galactosamide 2 has an unsymmetrical MLM with parallel molecular packing. The stereochemistry of the sugar hydroxy group proved to affect their hydrogen-bonding networks and induce the polymorphism of the MLM.

Lipid Nanotubes and Microtubes: Experimental Evidence for Unsymmetrical Monolayer Membrane Formation from Unsymmetrical Bolaamphiphiles

Unsymmetrical bolaamphiphiles, omega- [N-beta-D-glucopyranosylcarbamoyl] alkanoic acids, with even-numbered oligomethylene chains (12, 14, 16, 18, and 20 carbons) self-assembled in water to form lipid nano- and microtubes. The tubular assemblies were separated by centrifugation and examined by transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to study the molecular packing within the tubular membranes. The nanotubes encapsulated the staining reagent phosphotungstate, which revealed them to be hollow cylinders up to several hundred micrometers long with 30-43-nm outer diameters and 14-29-nm inner diameters. By comparing the membrane stacking periodicity obtained from powder X-ray diffraction analysis of the dehydrated tubes with the molecular packing within single crystals, we found that the nanotubes consist of an unsymmetrical monolayer lipid membrane (MLM) in which the molecules are packed in a parallel fashion. This suggests that the inner surface of the nanotubes is covered with carboxy headgroups and the outer surface with 1-glucosamide headgroups. The inner diameters of the lipid nanotubes could be controlled in the range 17.7-22.2 nm in steps of approximately 1.5 nm/two carbons by varying the oligomethylene spacer length. The microtubes had three types of molecular arrangements. The first type was a symmetrical MLM in which the molecules were packed in an antiparallel fashion. The other two types had unsymmetrical MLM stacking with head-to-head and head-to-tail motifs. Increasing the number of oligomethylene spacers stabilized the unsymmetrical MLM structure in both nano- and microtubes.

Efficient Synthesis of Unsymmetrical Bolaamphiphiles for Spontaneous Formation of Vesicles and Disks with a Transmembrane Organization

Unsymmetrical bolaamphiphiles 1a−1d bearing a neutral glycosidic polar head and an electropositive ammonium group at opposite ends of a polymethylene bridging spacer were efficiently synthesized. An additional alkoxy group was introduced at the anomeric site of the carbohydrate in order to yield anomerically defined compounds, to allow the modulation of hydrophobic−hydrophilic balance (HLB), and to increase the dissymmetry of the monomers. The self-assembling properties of the bolaphiles 1a−1d were investigated in both concentrated and more diluted aqueous media and were characterized in a variety of ways. An appropriate modulation of the HLB allowed us to obtain spontaneous formation of stable vesicles characterized by a transmembrane conformation of the lipids. Freeze fracture electron microscopy clearly demonstrated an unusual transformation of the vesicular systems into disks upon heating.

Supramolecular chemistry of cascade polymers: Construction, molecular inclusion, and inorganic connectivity

AbstractThe construction of cascade polymers with novel properties is discussed. A flexible amide‐based cascade architecture facilitates changes of the molecular hydrodynamic radius as a function of environmental pH, provided that the periphery is coated with ionizable functional groups (e.g., carboxylic acids or amines). Thus, it is possible to expand or contract the internal void domains within these cascades. By extension of the heteroatom connectivity, we have prepared a novel multifunctional molecule possessing a predetermined spherical morphology, that utilizes a ruthenium(II) metal center coordinated to two different orthogonal 2,2':6',2″‐terpyridine moieties to build the arm(s) of the cascade polymer. This technology permits the placement of multiple metal complexes at predetermined internal sites within the hydrophilic‐surfaced MicellaneTM framework. The combination of these two strategies to build cascade polymers allows the creation of an unsymmetrical bolaamphiphile constructed from two separate and distinct macromolecules. We are able to build cascade molecules either with a terpyridine unit inside or outside the polyamide sphere. The use of a connecting ruthenium(II) center allows the specific formation of a stable complex between the discrete cascade polymers.