Self-assembly Of Bolaamphiphiles Research Articles

Heparin binding induced supramolecular chirality into the self-assembly of perylenediimide bolaamphiphile.

Chirality is one of the hallmarks of biomolecules. Herein, we utilize heparin, a chiral biomolecule and potent drug, to induce chiral organization into the assembly of an achiral molecule. Polyanionic heparin binds with a dicationic perylenediimide derivative to induce supramolecular helical organization in aqueous medium as well as in a highly competitive cell culture medium.

Self-Assembly of Bolaamphiphiles into 2D Nanosheets via Synergistic and Meticulous Tailoring of Multiple Noncovalent Interactions.

A bolaamphiphile possessing a hydrophobic skeleton and two hydrophilic groups at both ends represents an important class of building blocks toward a rich variety of self-assembled materials for use in ion transport, optoelectronic devices, and drug and gene delivery. Herein, we report a one-step synthesis of an array of rationally designed anionic bolaamphiphiles and unravel the correlation between molecular structure of anionic bolaamphiphiles and their disparate self-assemblies via synergistic and meticulous tailoring of a set of interactions. Intriguingly, by delicately regulating the interactions among these supramolecular interactions, two-dimensional (2D) nanosheets are crafted via self-assembly of anionic bolaamphiphiles. Particularly, single-layered 2D nanosheets are formed through the synergy of aromatic π-π stacking, hydrophobic, hydrogen-bonding, and electrostatic repulsion interactions. In contrast, the selective converting of anionic headgroups of bolaamphiphiles into nonpolar alkyl chain screens the electrostatic repulsion between neighboring bolaamphiphiles while keeping the other segments of bolaamphiphiles intact, thereby allowing them to self-assemble into multilayered 2D nanosheets. Interestingly, the intrinsically charged 2D nanosheets could anchor oppositely charged metal nanoparticles via electrostatic attraction. Conceptually, anionic bolaamphiphile-derived 2D nanosheets may function as a substrate to position a diversity of nanocrystals and conjugated polymers for a broad range of applications in catalysis, optical devices, and photothermal therapy.

Coarse-grained molecular dynamics study of the self-assembly of polyphilic bolaamphiphiles using the SAFT-γ Mie force field

A methodology is outlined to parametrize coarse grained molecular models for the molecular dynamics simulation of liquid crystals.

Light-controlled self-assembly of a dithienylethene bolaamphiphile in water.

The self-assembly of bolaamphiphiles comprised of a central photochromic dithienylethene (DTE) chromophore was investigated in aqueous media. Irradiation at 254 nm induced a conversion from the open to closed states of the DTE chromophores. Whereas, in water, irradiation produced a photostationary state of 20 : 80 (open/closed), in methanol the ratio improved to 10 : 90 (open/closed). The open → closed transition was accompanied by the formation of 1D nanofibers during incubation in darkness.

A Self-Assembled Bicontinuous Cubic Phase with a Single-Diamond Network.

The first single-diamond cubic phase in a liquid crystal is reported. This skeletal structure with the space group is formed by self-assembly of bolaamphiphiles with swallow-tailed lateral chains. It consists of bundles of π-conjugated p-terphenyl rods fused into an infinite network by hydrogen-bonded spheres at tetrahedral four-way junctions. We also present a quantitative model relating molecular architecture to the space-filling requirements of six possible bicontinuous cubic phases, that is, the single- and double-network versions of gyroid, diamond, and "plumber's nightmare".

Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles.

The self-assembly and antimicrobial activity of two novel arginine-capped bola-amphiphile peptides, namely RA6R and RA9R (R, arginine; A, alanine) are investigated. RA6R does not self-assemble in water due to its high solubility, but RA9R self-assembles above a critical aggregation concentration into ordered nanofibers due to the high hydrophobicity of the A9block. The structure of the RA9R nanofibers is studied by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Circular dichroism spectroscopy shows that both RA6R and RA9R adopt coil conformations in water at low concentration, but only RA9R adopts a β-sheet conformation at high concentration. SAXS and differential scanning calorimetry are used to study RA6R and RA9R interactions with a mixed lipid membrane that models a bacterial cell wall, consisting of multilamellar 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine vesicles. Cytotoxicity studies show that RA6R is more cytocompatible than RA9R. RA6R has enhanced activity against the Gram-negative pathogen P. aeruginosa at a concentration where viability of mammalian cells is retained. RA9R has little antimicrobial activity, independently of concentration. Our results highlight the influence of the interplay between relative charge and hydrophobicity on the self-assembly, cytocompatibility, and bioactivity of peptide bola-amphiphiles.

Strain-Stiffening in Dynamic Supramolecular Fiber Networks.

The cytoskeleton is a highly adaptive network of filamentous proteins capable of stiffening under stress even as it dynamically assembles and disassembles with time constants of minutes. Synthetic materials that combine reversibility and strain-stiffening properties remain elusive. Here, strain-stiffening hydrogels that have dynamic fibrous polymers as their main structural components are reported. The fibers form via self-assembly of bolaamphiphiles (BA) in water and have a well-defined cross-section of 9 to 10 molecules. Fiber length recovery after sonication, H/D exchange experiments, and rheology confirm the dynamic nature of the fibers. Cross-linking of the fibers yields strain-stiffening, self-healing hydrogels that closely mimic the mechanics of biological networks, with mechanical properties that can be modulated by chemical modification of the components. Comparison of the supramolecular networks with covalently fixated networks shows that the noncovalent nature of the fibers limits the maximum stress that fibers can bear and, hence, limits the range of stiffening.

Photoinduced Intermolecular Electron Transfer Mediated by the Colloidal Tyrosyl Bolaamphiphile Assembly.

The self-assembly of tyrosyl bolaamphiphiles is exploited to create a colloidal protein-like host matrix, upon which sacrificial electron-donor molecules associate to create a photosystem II (PSII) mimetic electron-relay system. This system harnesses the tyrosine phenol groups abundant on the surface of the assemblies to mediate photoinduced intermolecular electron transfer. Compared with the l-tyrosine molecules, the tyrosyl bolaamphiphile assembly facilitates electron transfer from the sacrificial electron donor to the oxidized photosensitizer. The enhanced electron relay is likely to be driven by the host function of the assembly associated with the sacrificial electron donor and by the suppression of the oxidative cross-linking of phenoxyl radicals. The tyrosyl bolaamphiphile assembly is advantageous in the construction of a PSII mimetic system with a protein-like nature and displaying biochemical functions.

Modeling the Self-Assembly of Bolaamphiphiles under Nanoconfinement by Coarse-Grained Molecular Dynamics.

Novel and complex nanostructures of amphiphiles assemblies facilitate realizing of many practical applications in nanotechnologies. Under different physical conditions, amphiphiles can form various morphologies. In this article, the self-assembly of bolaamphiphiles was investigated under the cylindrical confinement of carbon nanotubes by coarse-grained molecular dynamics simulation. We found that bolaamphiphiles inside a carbon nanotube with a relatively large diameter tended to self-assemble into curved cylindrical micelles, and further some of these micelles can form double helix structures which were not observed in bulk solutions. We develop an effective method to characterize different morphologies. Our analysis results showed that the formation of double helix and other amorphous morphologies of micelles in carbon nanotubes is not induced by the conformational variation of bolaamphiphiles. Moreover, through examining the potential energies of different structures, we infer that it is entropy which leads micelles to bend even to form double stranded helix structures. In addition, we analyzed the sizes of micelles and find the scission and recombination of micelles during the double helix formation process. This work indicates that the confinement of carbon nanotube is an available method to produce complex nanostructures and provides some new insights of the self-assembly of bolaamphiphiles.

Low molecular weight hydrogels derived from urea based-bolaamphiphiles as new injectable biomaterials.

There is a critical need for soft materials in the field of regenerative medicine and tissue engineering. However, designing injectable hydrogel scaffolds encompassing both adequate mechanical and biological properties remains a key challenge for invivo applications. Here we use a bottom-up approach for synthesizing supramolecular gels to generate novel biomaterial candidates. We evaluated the low molecular weight gels candidates invivo and identified one urea-containing molecule, compound 16, that avoid foreign body reactions in mice. The self-assembly of bolaamphiphiles creates a unique hydrogel supramolecular structures featuring fast gelation kinetics, high elastic moduli, thixotropic, and thermal reversibility properties. This soft material, which inhibits recognition by macrophages and fibrous deposition, exhibits long-term stability after invivo injection.

An Unconventional Zwitterionic Bolaamphiphile Containing PEG as Spacer Chain: Surface Tension and Self-Assembly Behavior.

Monolayer lipid membrane formation based on self-assembly of bolaamphiphiles containing hydrophobic spacer are well-established in the literature, but monolayer vesicle formation by so-called hydrophilic poly(ethylene glycol) (PEG) spacer has not been reported to date. Here, a novel l-cysteine-derived bolaamphiphile with PEG as spacer has been developed and characterized. The interfacial properties and the solution behavior of the amphiphile were investigated in pH 7.0 at 25 °C. The self-assembly properties of the bolaamphiphile in aqueous buffer were investigated by using different techniques, such as surface tensiometry, fluorescence spectroscopy, UV-vis spectroscopy, isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy, and atomic force microscopy. Surprisingly, despite having so-called polar spacer in between two polar head groups, it exhibits formation of microstructures in aqueous buffer as well as in water at 25 °C. The molecule undergoes self-organization leading to the formation of monolayer vesicles with hydrodynamic diameters between 100 and 250 nm in a wide range of concentration. The thermodynamic parameters clearly suggest that the aggregate formation is mainly driven by the hydrophobic effect. The monolayer vesicles were found to form at a very low concentration (≥0.63 mM) and within a wide pH range (2-10). The vesicles exhibit excellent shelf life at physiological temperature.

Visualization of periodic electric polarizability of helical nanofibers formed by self-assembly of nucleotide-bearing bolaamphiphiles and natural-source DNA as a template.

The possibility of fabricating DNA-based electronics has attracted considerable attention, but constructing robust, functional DNA nanowires on hard substrates has proven to be difficult. This paper describes the production of robust one-dimensional nanofibers by self-assembly of 1,18-nucleotide-bearing bolaamphiphiles templated by salmon sperm DNA. Electrostatic force microscopy measurements of the nanofibers on a highly oriented pyrolytic graphite substrate revealed that they showed electric polarizability that varied periodically with a pitch of 20-30 nm. Atomic force microscopy, gel electrophoresis, and circular dichroism spectroscopy suggested that the periodic polarizability was derived from right-handed helicity induced by the template DNA. Salmon sperm DNA itself did not show electric polarizability.

Hemoglobin-mimetic oxygen adsorbent prepared via self-assembly of cysteinyl bolaamphiphiles

In this study, a novel cysteinyl bolaamphiphilic molecule was synthesized and its self-assembled planar suprastructure was applied as a biomimetic matrix to create a hemoglobin-mimetic oxygen adsorbent that exploits the ability of cysteine thiols to bind hemin. Self-assembly of the cysteinyl bolaamphiphilic molecule exposed cysteine thiols on its surface in the presence of β-mercaptoethanol, known to reduce disulfide bonds, without which, helically coiled structures were generated. The self-assembled planar structure was used as a soft matrix to create a hemoglobin-mimetic oxygen adsorbent. The surface-exposed cysteine thiols were used to attach hemin, producing a hemin-bound, planar structure mimicking hemoglobin. This hemoglobin mimic strongly adsorbed oxygen and remained stable up to 50°C. The cysteinyl bolaamphiphile self-assembled structure provided a biomimetic platform that allowed for the association of biological substances in a manner similar to natural proteins.

An enzyme-coupled artificial photosynthesis system prepared from antenna protein-mimetic tyrosyl bolaamphiphile self-assembly.

An artificial photosynthesis system coupled with an enzyme was constructed using the nanospherical self-assembly of tyrosyl bolaamphiphiles, which worked as a host matrix exhibiting an antenna effect that allowed enhanced energy transfer to the ZnDPEG photosensitizer. The excited electrons from the photosensitizer were transferred to NAD+ to produce NADH, which subsequently initiated the conversion of an aldehyde to ethanol by alcohol dehydrogenase. Production of NADH and ethanol was enhanced by increasing the concentration of tyrosyl bolaamphiphiles. Spectroscopic investigations proved that the photosensitizer closely associated with the surface of the bolaamphiphile assembly through hydrogen bonds that allowed energy transfer between the host matrix and the photosensitizer. This study demonstrates that the self-assembly of bolaamphiphiles could be applicable to the construction of biomimetic energy systems exploiting biochemical activity.

Effects of transition metal ions on the catalytic activity of carbonic anhydrase mimics

Many carbonic anhydrase (CA)–mimetic catalysts have active sites composed of a Zn ion coordinated with multiple nitrogens of azacyclic compounds. In this study, some divalent transition metal ions (Co2+, Cd2+, and Ni2+) were examined as potential substitutes for the Zn cofactor when preparing CA–mimetic catalysts by means of self-assembly of histidyl bolaamphiphiles. The self-assembly of histidyl bolaamphiphiles yielded a densely packed histidine imidazole sites offering metal complexation places similar to the triple-histidine imidazoles of natural CA active sites. In the catalytic hydrolysis of p-nitrophenyl acetate, the catalytic efficiency of the mimetic catalysts agreed with the order of catalytic activities of metal–substituted carbonic anhydrases: Zn>Co>Cd≈Ni; activation energy of the CA–mimetic catalysts and practical CO2 hydration efficiency also had the same order. However, Co showed better catalytic activity than Zn when the concentrations of metal salts were higher than 0.1mM because of weakened inhibition by the counter anion. This study elucidated the effect of transition metal ions on the catalytic efficiency of a CA–mimetic catalyst, with emphasis on the coordination of transition metal ions.

Biomimetic Catalytic and Sensing Cascades Built with Two Designer Bolaamphiphilic Self-Assemblies.

A system performing both a catalytic hydrolysis reaction and the direct optical monitoring of the product was created by the combination of two bolaamphiphile self-assemblies. Two bolaamphiphilic self-assemblies were applied as a biomimetic catalyst of p-nitrophenyl acetate (p-NPA) hydrolysis and an optical sensor probe that detects p-NPA hydrolysis through photoluminescence quenching by p-nitrophenol (p-NP), the product of p-NPA hydrolysis. One bolaamphiphilic self-assembly with a histidine moiety catalytically hydrolyzed the p-NPA substrate, and the other self-assembly of tyrosyl bolaamphiphile monitored the product of p-NP by photoluminescence quenching. The progression of the reaction and quenching degree were adjusted by controlling the quantity of histidyl and tyrosyl self-assemblies, respectively. The reaction and subsequent sensing cascade could be interrupted by a reducing agent. The addition of NaBH4 induced the chemical conversion of p-NP to p-aminophenol, which retarded photoluminescence quenching. Thus, it was demonstrated that hydrolysis of an organic substrate and subsequent monitoring of the hydrolysis reaction could be achieved through a combination of independent bolaamphiphilic self-assemblies. This study demonstrated the construction of a catalytic reaction and detection system incorporating designer biomimetic self-assemblies whose functionalities were devised to realize deliberate functions.

Water-soluble nano-fluorogens fabricated by self-assembly of bolaamphiphiles bearing AIE moieties: towards application in cell imaging.

Nano-fluorogens with a mono-molecule layered structure are fabricated by self-assembly of a new bolaamphiphile bearing a tetraphenylethene moiety. The nano-fluorogens show good water-solubility, biocompatibility, and strong emission with a quantum yield as high as 15%. The nano-fluorogens, as prepared, are successfully applied to label and map HeLa cells. The images obtained have high contrast and resolution, showing a promising potential for fluorescence detection in bio-related systems.

Peroxidase-like oxidative activity of a manganese-coordinated histidyl bolaamphiphile self-assembly.

A peroxidase-like catalyst was constructed through the self-assembly of histidyl bolaamphiphiles coordinated to Mn(2+) ions. The prepared catalyst exhibited oxidation activity for the organic substrate o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2). The histidyl bolaamphiphiles of bis(N-alpha-amido-histidine)-1,7-heptane dicarboxylates self-assembled to make spherical structures in an aqueous solution. Subsequent association of Mn(2+) ions with the histidyl imidazoles in the self-assembly produced catalytic active sites. The optimal Mn(2+) ion concentration was determined and coordination of the Mn(2+) ion with multiple histidine imidazoles was investigated using spectroscopy analysis. The activation energy of the produced catalysts was 55.0 kJ mol(-1), which was comparable to other peroxidase-mimetic catalysts. A detailed kinetics study revealed that the prepared catalyst followed a ping-pong mechanism and that the turnover reaction was promoted by increasing the substrate concentration. Finally, application of the prepared catalyst for glucose detection was demonstrated through cascade enzyme catalysis. This study demonstrated a facile way to prepare an enzyme-mimetic catalyst through the self-assembly of an amphiphilic molecule containing amino acid segments.

Concentration-dependent and light-responsive self-assembly of bolaamphiphiles bearing α-cyanostilbene based photochromophore.

In this paper, a new bolaamphiphile bearing 1-cyano-1,2-bis(phenyl)ethene (CNBE) has been synthesized. The self-assembly of this molecule in aqueous solution is concentration-dependent. Two distinct morphologies, monomolecular layered lamellas and helical nanofibres have been obtained with the as-prepared molecular configuration. Note worthily, the helical nanofibres provide an experimental evidence for the pure twisted structure in the liquid crystals, which is theoretically proposed by De Gennes. Due to the photoisomerization of CNBE, the self-assembled nanostructures undergo morphological changes upon irradiation. Although various nanostructures were observed in the solution-state, only nanofibres were obtained after the solution was cast on a substrate, which was attributed to a strong dewetting effect. This work illustrates concentration-dependent and light-responsive self-assembly and provides a novel avenue for fabricating smart soft materials.

Evaluation of photoluminescence quenching for assessing the binding of nitroaromatic compounds to a tyrosyl bolaamphiphile self-assembly.

Quenching of a fluorophore is significantly influenced by the molecular structure of the quencher. In this study, photoluminescence quenching by nitroaromatic compounds was evaluated to assess the molecular interaction between nitroaromatic molecules and the photoluminescent tyrosyl bolaamphiphile self-assembly, a nanoscale optical photoluminescent probe. Both the aromatic structure and hydrophilic functional groups of the nitroaromatic quencher molecules significantly enhanced the binding of quencher molecules to the photoluminescent probe. UV-vis spectroscopy supported the non-covalent molecular association of aromatic stacking, which significantly increased the quenching efficiency compared to an aliphatic compound. The hydrophilic groups of the nitroaromatic compounds also enhanced the photoluminescence quenching, because of the hydrophilic nature of the phenol moiety. Energy levels of the photoluminescent probe and quencher molecules, along with molecular interactions, were investigated to explain the quenching mechanism. Density functional theory (DFT) calculation was performed to provide the energy levels and charge density of the nitroaromatic compounds. The information presented in this study regarding the structural effect of a quencher molecule on the photoluminescence quenching of the photoluminescent probe will be useful in designing binding motifs of future photoluminescent probes.