Self-assembled multivalent carbohydrate ligands

Materials that display multiple carbohydrate residues have gained much attention due to their potential to inhibit or modulate biological multivalent interactions. These materials can be grouped accordingly to the way they are prepared, as unimolecular or as self-assembled systems. Both systems take advantage of the fact that multivalent interactions have significantly higher binding affinity than the corresponding monovalent interactions. The self-assembled system is a more recent field of research compared to the unimolecular system. In this review, we describe current efforts to realize multivalent carbohydrate interactions from the perspective of synthetic self-assembled systems. We limit the scope to self-assembled systems that are stable, soluble in aqueous solution and morphologically discrete. We grouped them into two separate categories. In the first category carbohydrate ligands self-assemble onto a pre-organized nanostructure, and in the second carbohydrate-conjugated block molecules spontaneously assemble to construct morphologically distinct nanostructures.     

Directed self-assembly of functionalized silica nanoparticles on molecular printboards through multivalent supramolecular interactions

Silica nanoparticles functionalized with beta-cyclodextrin (CD) host molecules (5) have been prepared by reacting carboxylic active ester-terminated silica nanoparticles (4) with CD heptamine. Silica nanoparticles functionalized with glucosamine (6), having similar surface properties as 5 but lacking the host-guest recognition motif, were used to perform blank experiments. The CD-functionalized silica nanoparticles 5 were determined by TEM to be 55 +/- 6 nm in size. They exhibited pH-dependent aggregation, which is explained by the presence of free amino and carboxylic acid groups on the particle surface, which was corroborated by zeta potential measurements. The functionalization with CD was further confirmed by host-guest studies in solution and at CD-functionalized silicon substrates. The addition of an adamantyl-terminated dendrimer, capable of multivalent host-guest binding with CD, led to strong aggregation of the CD particles 5, but not of the glucosamine-functionalized 6. Furthermore, 5 gave strong adsorption to CD monolayers on silicon onto which adamantyl-terminated dendrimers were adsorbed, whereas 6 did not. The good discrimination between dendrimer-covered and uncovered areas of the CD monolayer substrates allowed the directed self-assembly of the silica particles 5 onto dendrimer-patterned areas created by microcontact printing.     

Controlled formation of gold nanoparticle dimers using multivalent thiol ligands

Approaches for the controlled formation of gold nanoparticle dimers are investigated. These are based on a locally confined surface modification of gold nanoparticles followed by bridging two particles with an organic linker. A key factor in these approaches is the use of multivalent ligands. Citrate-stabilized gold nanoparticles are immobilized on a glass surface and mono- and multivalent thiol ligands are investigated regarding their ability to inactivate the nanoparticles sites facing away from the glass. A successful locally confined functionalization is only possible if multivalent ligands are used in this step. The application of monovalent ligands results in less stable particles without a permanent regioselective functionalization. This result can be explained by the dynamic equilibrium between bound and free ligands. Subsequently, the sites of the nanoparticles previously bound to the glass surface are functionalized with thiol ligands additionally bearing a reactive group. Approaches using dithiol linkers, diamine linkers, and coupling complementary functionalized particles are investigated. The highest yield of stable dimers is obtained from conditions where nanoparticles which are regioselectively functionalized with an N-hydroxysuccinimide ester are reacted with complementary amino-functionalized particles. The application of nanoparticles with activated carboxyl groups is essential since standard carboxyl activation agents induce an aggregation of the nanoparticles due to a reaction with remaining citrate molecules on the nanoparticle surface which reduces significantly electrostatic stabilization. This versatile approach using complementary regioselective with multivalent ligands functionalized nanoparticles may be also used for the coupling of particles with different size, shape, or composition, as well as a control of the interparticle distance.     

Understanding self-assembly of rod-coil copolymer in nanoslits

Rod-coil diblock copolymers are a special kind of molecule containing a rigid rod and a flexible part. We present a systematic study on self-assembly of the rod-coil copolymers in nanoslits using a hybrid density functional theory. The self-assembly of the rod-coil molecule is driven by the bulk concentration, and there exists a critical bulk concentration beyond which the rod-coil molecule self-assembled into ordered lamellar structures in the slit, otherwise it is in a disordered state. By monitoring the effect of the interaction (epsilon(TT)(*)) of molecular tail on the self-assembly, we found that in the nanoslit of H=13sigma, it is at epsilon(TT)(*)=8 rather than epsilon(TT)(*)=10 or epsilon(TT)(*)=12 that the minimal critical bulk concentration occurs. It may be because the strong tail-tail interaction leads to aggregation of the copolymer molecules in bulk phase, and the resulting supramolecular structures are fairly difficult to enter the slit due to the depletion effect. At a fixed slit, the structural evolution of the self-assembled film with the bulk concentration is observed, including trilayer and five-layer lamellar structures, smectic-A, smectic-C, and a mixture of smectic-A and smectic-C liquid crystal phases and so on. We found that the critical bulk concentration, corresponding to the disordered-ordered phase transition, greatly depends on the separation between two walls, and it changes periodically with the increase of the slit width. In addition, it is also found that the molecular flexibility is one of key factors determining the self-assembled structure in the slit, and the critical bulk density increases with the molecular flexibility.     

Hierarchical self-assembly of noncovalent amphiphiles

Amphiphiles defined by noncovalent inclusion complexes between an alkylated beta-cyclodextrin and PEG-conjugated guests assemble into higher-ordered structures whose thermodynamic stability reflects that of the defining intermolecular interactions.     

Confined supramolecular nanostructures of mesogen-bearing amphiphiles

Stable surface nanostructures with different morphology have been successfully constructed by modifying the chemical structure of synthetic amphiphiles; by introducing mesogenic groups into bolaform amphiphiles, stable spaghetti-like or stripe-like nanostructures can be obtained; it is believed that such a kind of surface structure could be used for templating synthesis and assembly.     

超分子自组装中的非共价键协同作用

本文综述了近年来氢键、π-π堆积作用、配位作用、供体-受体相互作用和疏溶剂作用等多种非共价键协同作用在超分子自组装研究中的新进展。     

Controlled self-assembly of squaraines to 1D supramolecular architectures with high molar absorptivity

A tailor made squaraine dye upon binding with Ca2+ self-assembles to form a spherical micellar assembly that reorganises to thermodynamically stable 1D cylindrical rods with high molar absorptivity.     

Flexible bidentate pyridine and chiral ligands in the self-assembly of supramolecular 3-D cages

Discrete, nanoscopic 3-D cages are prepared in high yield via coordination-driven self-assembly from a variety of building blocks, including bidentate 3-substituted pyridines, chiral, and silicon-based tripods. All are characterized by NMR ((31)P, (1)H) and electrospray ionization mass spectrometry.     

Supramolecular reactor from self-assembly of rod-coil molecule in aqueous environment

We synthesized an amphiphilic coil-rod-coil triblock molecule consisting of hexa-p-phenylene as a rod block and poly(ethylene oxide) with the number of repeating units of 17 as coil blocks and investigated aggregation behavior in aqueous environment. The rod-coil molecule was observed to aggregate into discrete micelles consisting of hydrophobic disklike rod bundles encapsulated by hydrophilic poly(ethylene oxide) coils. The aromatic bundles of the micelles were demonstrated to be used as an efficient supramolecular reactor for the room temperature Suzuki cross-coupling reaction of a wide range of aryl halides, including even aryl chlorides with phenylboronic acids in aqueous environment. These results demonstrate that self-assembly of amphiphilic rod-coil molecules can provide a useful strategy to construct an efficient supramolecular reactor for aromatic coupling reaction.     

Synthesis and hierarchical self-assembly of cavity-containing facial amphiphiles

The synthesis and aggregation behavior of cavity-containing facial amphiphiles is described. The molecules consist of a glycoluril-based rigid cavity functionalized with two water-soluble benzoate groups. By specific molecular recognition processes in water, the amphiphilic hosts self-assemble in a hierarchical process to form arrays of molecules. Depending on the counterions, these arrays can be assembled into well-defined aggregates of mesoscopic size. The size and shape of the aggregates can be tuned by variations in the size and substitution pattern of the cavities of the host molecules.     

Versatility of cyclodextrins in self-assembly systems of amphiphiles

Recently, cyclodextrins (CDs) were found to play important yet complicated (or even apparently opposite sometimes) roles in self-assembly systems of amphiphiles or surfactants. Herein, we try to review and clarify the versatility of CDs in surfactant assembly systems by 1) classifying the roles played by CDs into two groups (modulator and building unit) and four subgroups (destructive and constructive modulators, amphiphilic and unamphiphilic building units), 2) comparing these subgroups, and 3) analyzing mechanisms. As a modulator, although CDs by themselves do not participate into the final surfactant aggregates, they can greatly affect the aggregates in two ways. In most cases CDs will destroy the aggregates by depleting surfactant molecules from the aggregates (destructive), or in certain cases CDs can promote the aggregates to grow by selectively removing the less-aggregatable surfactant molecules from the aggregates (constructive). As an amphiphilic building unit, CDs can be chemically (by chemical bonds) or physically (by host–guest interaction) attached to a hydrophobic moiety, and the resultant compounds act as classic amphiphiles. As an unamphiphilic building unit, CD/surfactant complexes or even CDs on their own can assemble into aggregates in an unconventional, unamphiphilic manner driven by CD–CD H-bonds. Moreover, special emphasis is put on two recently appeared aspects: the constructive modulator and unamphiphilic building unit.     

An extraordinary cylinder-to-cylinder transition in the aqueous assemblies of fluorescently labeled rod-coil amphiphiles

We report an unprecedented cylinder-to-cylinder transformation in the self-assemblies of pyrene-labeled rod-coil molecules in water. The extraordinary morphological transformation can be monitored by a fluorescence variation from exciplex to excimer emissions, suggesting the rod-packing transition from antiparallel to interdigitated arrangements as a function of PEO coil length.     

Bioinspired self-assembly supramolecular hydrogel for ocular drug delivery

Based on a recent report concerning endogenous agents (i.e., pyridoxal phosphate, adenosine triphosphate, adenosine monophosphate, folinic acid) that modulate the oligomerization of apoptosis-associated speck-like protein (ASC) via the peptide epitope of KKFKLKL, we rationally designed and synthesized a nonapeptide (NapFFKKFKLKL), which can co-assemble with dexamethasone sodium phosphate (Dexp) to generate a NapFFKKFKLKL/Dexp supramolecular hydrogel for ocular drug delivery. The NapFFKKFKLKL/Dexp hydrogel formed instantly after the complexation of NapFFKKFKLKL with Dexp in aqueous solution. The formed supramolecular hydrogels were thoroughly characterized by transmission electron microscopy (TEM), fluorescent spectrum, circular dichroism (CD) spectra and rheology. The peptide concentration significantly affected the in vitro release behavior of Dexp from the supramolecular hydrogel, and the higher peptide concentration resulted in the slower drug release. Following a single intravitreal injection, the proposed NapFFKKFKLKL/Dexp hydrogel displayed good intraocular biocompatibility without having an adverse impact on the retinal architecture and eyesight functions during one month of follow-up. Using an experimental autoimmune uveitis (EAU) rat model, we demonstrated that the resulting NapFFKKFKLKL/Dexp hydrogel had potent capacity to alleviate the intraocular inflammation and retain the morphology of retinal architecture. Overall, the resulting NapFFKKFKLKL/Dexp hydrogel may be a promising drug carrier system to treat various posterior disorders (i.e., uveitis).     

Coordination-driven self-assembly of predesigned supramolecular triangles

The design and self-assembly of three supramolecular triangles is described. A novel 60 degrees corner unit directs the exclusive formation of triangular assemblies that are not in detectable equilibrium with other macrocycles. The resulting triangles have sides ranging from 2.7 to 3.5 nm in length and molecular masses as high as 5396 amu. The crystal structure of one of the assemblies shows an approximately 1.4 nm cavity; the crystal packing forms open, triangular channels. The characterization of the supramolecular triangles by multinuclear NMR, elemental analysis, and electrospray mass spectrometry is also reported.     

Synthesis and characterization of maltose-based amphiphiles as supramolecular hydrogelators

Low molecular mass amphiphilic glycolipids have been prepared by linking a maltose polar head and a hydrophobic linear chain either by amidation or copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. The liquid crystalline properties of these amphiphilic materials have been characterized. The influence of the chemical structure of these glycolipids on the gelation properties in water has also been studied. Glycolipids obtained by the click coupling of the two components give rise to stable hydrogels at room temperature. The fibrillar structure of supramolecular hydrogels obtained by the self-assembly of these gelators have been characterized by electron microscopy. Fibers showed some torsion, which could be related with a chiral supramolecular arrangement of amphiphiles, as confirmed by circular dichroism (CD). The sol-gel transition temperature was also determined by differential scanning calorimetry (DSC) and NMR.