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.     

Combinatorial library of low molecular-weight organo- and hydrogelators based on glycosylated amino acid derivatives by solid-phase synthesis

A combinatorial approach for the synthesis of supramolecular gelators as new organic materials is described herein. In the course of the development of a convenient and flexible solid-phase synthesis of the artificial glycolipids, some of these compounds were accidentally found to act as low molecular-weight gelators toward organic solvents. Using this combinatorial solid-phase synthesis of glycosylated amino acetates, screening and optimization of low molecular-weight organo/hydro-gelators were efficiently carried out. We found that an N-acetyl-galactosamine-appended amino acid ester (GalNAc-aa) efficiently gelates a broad spectrum of organic solvents. More interestingly, some GalNAc-aa derivatives displayed an excellent hydrogelation capability. Transmission electron microscopy, scanning electron microscopy, confocal laser scanning microscopy, and FT-IR were used for characterization of the gel structure. It is indicated that supramolecular fibers supported by strong hydrogen-bonding networks are entangled so that the resulting spaces can immobilize a number of solvent molecules effectively. In addition, the supramolecular hydrogel consisting of GalNAc-suc-glu(O-methyl-cyc-pentyl)(2) is stable even under high salt concentrations probably due to its nonionic character and as a result, a native protein is successfully entrapped in the gel matrix without denaturation.     

First thermally responsive supramolecular polymer based on glycosylated amino acid

In materials science, a dynamic property sensitive to an environmental change (heat, light, electric current, pH, and other chemical or physical changes) is indispensable for intelligent materials. Such organic materials, however, are very limited even in conventional polymers. This paper clearly demonstrates that, regardless of the low molecular weight, a glycosylated amino acid derivative newly screened by a combinatorial method forms a macroscopic supramolecular hydrogel that reversibly swells or shrinks in response to the external temperature. Using the unique thermal response of the present hydrogel, we carried out the controlled release of DNA and the perfect removal of bisphenol A from the polluted water. Recently, advanced supramolecular polymers, in which monomers are noncovalently connected, are expected to be highly advantageous over traditional polymers because of their tunable and recyclable characteristics. The present result newly confers a dynamic feature on the supramolecular polymers, which is desirable for the sophisticated application in many fields.     

Multifunctional, polymorphic, ionic fullerene supramolecular materials: self-assembly and thermotropic properties

An N-methylfulleropyrrolidine (2) bearing three eicosyloxy chains on the laterally substituted phenyl group can be further functionalized to give the ionic fullerene derivative, i.e., N,N-dimethylfulleropyrrolidinium iodide (1). The spectroscopic, electrochemical, self-assembly, and liquid crystalline properties of 1 have been investigated and compared to its neutral precursor 2. Changes in electronic structure upon ionization are observed in the UV spectra. Additionally, a positive potential shift of electrochemical reductions for 1 compared to those of 2 is noted in both homogeneous solution and film state. Driven by the π-π, van der Waals, and electrostatic interactions, the ionic compound 1 is able to form a variety of functional and polymorphic self-assembled structures both from solution and on substrates, including hierarchically organized flakelike microparticles with high water repellency, doughnut-shaped objects with rough surfaces, and long one-dimensional C(60) nanowires (>1 μm). The thermotropic behavior of 1 has also been investigated, and a smectic liquid crystalline phase was observed at elevated temperatures. Further investigations of the thermotropic behavior of 1 revealed that a deionization back-reaction from 1 to the neutral precursor 2 gradually occurred. The mechanism of this deionization reaction is presented and discussed. These investigations provide insight into the effects of added ionicity to alkylated fullerene derivatives, in particular on their self-assembly features and functionality.     

Interaction between uracil nucleobase and phenylalanine amino acid: the role of sodium cation in stacking

The stacking interactions in the uracil:phenylalanine (U:PHE) and (U:PHE)···Na⁺ complexes have been studied at different levels of theory, in which the structures were optimized by both standard and gradient counterpoise corrected methods. The Na⁺ cation can interact with different sites of stacked U:PHE unit. The geometrical parameters of the optimized structures and the calculated binding energies reveal the influence of cation interaction on π–π stacking and vice versa. The interplay between π–π stacking and cation interaction has also been investigated by topological analysis of electron charge density using atoms in molecules (AIM) method. A good agreement between the results of AIM analysis and calculated binding energies has been observed in dimer and complexes.     

Influence of the nucleobase and anchimeric assistance of the carboxyl acid groups in the hydrolysis of amino acid nucleoside phosphoramidates

Nucleoside phosphoramidates (NPs) are a class of nucleotide analogues that has been developed as potential antiviral/antitumor prodrugs. Recently, we have shown that some amino acid nucleoside phosphoramidates (aaNPs) can act as substrates for viral polymerases like HIV‐1 RT. Herein, we report the synthesis and hydrolysis of a series of new aaNPs, containing either natural or modified nucleobases to define the basis for their differential reactivity. Aqueous stability, kinetics, and hydrolysis pathways were studied by NMR spectroscopy at different solution pD values (5–7) and temperatures. It was observed that the kinetics and mechanism (P? N and/or P? O bond cleavage) of the hydrolysis reaction largely depend on the nature of the nucleobase and amino acid moieties. Aspartyl NPs were found to be more reactive than Gly or β‐Ala NPs. For aspartyl NPs, the order of reactivity of the nucleobase was 1‐deazaadenine>7‐deazaadenine>adenine>thymine≥3‐deazaadenine. Notably, neutral aqueous solutions of Asp‐1‐deaza‐dAMP degraded spontaneously even at 4 °C through exclusive P? O bond hydrolysis (a 50‐fold reactivity difference for Asp‐1‐deaza‐dAMP vs. Asp‐3‐deaza‐dAMP at pD 5 and 70 °C). Conformational studies by NMR spectroscopy and molecular modeling suggest the involvement of the protonated N3 atom in adenine and 1‐ and 7‐deazaadenine in the intramolecular catalysis of the hydrolysis reaction through the rare syn conformation.     

Superior SWNT dispersion by amino acid based amphiphiles: designing biocompatible cationic nanohybrids

Stable aqueous SWNT dispersion up to 92% was achieved using amino acid based amphiphiles through a structure-property investigation. The nanohybrids showed remarkable serum stability and biocompatibility to mammalian cells.     

Recent advances in biocompatible supramolecular assemblies for biomolecular detection and delivery

Inspired by sophisticated biological structures and their physiological processes,supramolecular chemistry has been developed for understanding and mimicking the behaviors of natural species. Through spontaneous self-assembly of functional building blocks,we are able to control the structures and regulate the functions of resulting supramolecular assemblies.Up to now,numerous functional supramolecular assemblies have been constructed and successfully employed as molecular devices, machines and biological diagnostic platforms.This review will focus on molecular structures of functional molecular building blocks and their assembled superstructures for biological detection and delivery.     

New l-valine-based hydrogelators: formation of supramolecular hydrogels

New l-valine derivatives, which have a positively charged group, function as excellent hydrogelators that can gel pure water, saline, and aqueous solutions containing inorganic acids and salts at 0.2 wt %.     

Melamine driven supramolecular self‐assembly of nucleobase derivatives in water

Water‐soluble supramolecular polymers, especially made up of biomolecules, are ideally suited to build new biomaterials that can mimic or interact with dynamic, biological environments. Here, two derivatives from thymine (T), that is N‐[2‐(3,4‐Dihydro‐5‐methyl‐2,4‐dioxo‐1(2H)‐pyrimidinyl)acetyl]‐L‐phenylalanine (T‐phe) and N‐(2‐Aminoethyl)‐3,4‐dihydro‐5‐methyl‐2,4‐dioxo‐1(2H)‐pyrimidineacetamide (T‐NH₂) were synthesized. Then the optimal condition for self‐assembly of T‐phe and T‐NH₂ driven by melamine (M) was explored. It was observed that M/T kept at 1:3 with equivalent T‐phe and T‐NH₂ under neutral environment resulted in long fibers (>1 μm) with extremely high aspect ratios, which suggested that electrostatic and π‐stacking interactions could be effectively orchestrated by hydrogen bonds to direct the hierarchical assembly. Furthermore, hydrogels were spontaneously generated with a concentrated solution of T‐phe, T‐NH₂, and M due to the fibril entanglement. Given its biomimetic nature and efficient self‐assembly process, this newly developed supramolecular polymer stacked by tetrameric structures represented an innovative concept and pathway for novel bio‐inspired materials. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 789–796     

Remarkable supramolecular catalysis of glycoside hydrolysis by a cyclodextrin cyanohydrin

(6AR,6DR)-6A,6D-di-C-cyano-beta-cyclodextrin (3) was synthesized and shown to catalyze hydrolysis of nitrophenyl glycosides with the reaction following Michaelis-Menten kinetics. At pH 7.4 and 25 degrees C, hydrolysis of 4-nitrophenyl-beta-glucopyranoside (2) was catalyzed with KM = 15 mM, kcat = 8.2 x 10-6 s-1, and kcat/kuncat = 1217. Catalysis was observed with concentration of 3 as low as 10 muM. Hydrolysis of the corresponding alpha-glucoside, alpha-galactoside, alpha-mannoside, and 2-nitrophenyl-beta-galactoside was also catalyzed by 3, with kcat/kuncat ranging from 283 to 2147. A series of analogues of 3 was prepared and investigated for catalysis of the hydrolysis of 2: (6AR,6DR)-6A,6D-di-C-propyl-beta-cyclodextrin (9) was not catalytic, while 6A,6D-di-C-cyano-6A,6D-dideoxy-beta-cyclodextrin (12) had a low catalytic activity (kcat/kuncat = 4). A kcat/kuncat = 48 was found for 6A,6D-dialdehydo-beta-cyclodextrin dihydrate (11). It was proposed that 3 acts by general acid catalysis on the bound substrate.     

Multifunctional triazolylferrocenyl Janus dendron: Nanoparticle stabilizer,smart drug carrier and supramolecular nanoreactor

Owing to their unique broken symmetry, amphiphilic Janus dendrimers and dendons provide fascinating properties for material, biological, pharmaceutical and biomedical applications. The integration of various organometallic moieties into these macromolecules will further offer the opportunity to form complex and intelligent architectures and materials. Here, we report a novel, simple and multifunctional Janus dendron containing redox‐reversible hydrophobic ferrocene (Fc) unit, complexing‐effective 1,2,3‐triazole ligand and biocompatible hydrophilic triethylene glycol termini. Silver and gold nanoparticles were firstly successfully prepared by using the Janus dendron as the reducing agent of Au(III) and Ag(I), and the stabilizer of the corresponding nanoparticles. The redox response of the Fc moiety was then employed to trigger the release of model drug, rhodamine B, encapsulated in supramolecular micelles formed by the self‐assembly of the Janus dendron. Finally, the precise and excellent metal‐complexing ability of the triazole group in this dendron was fully utilized to stabilize a water‐soluble Cu(I) catalyst, forming supramolecular nanoreactors for the catalysis of the copper(I)‐catalyzed azide alkyne cycloaddition click reaction in only water. The multifunctional characteristics of this dendron highlight the potential for organometallic Janus dendrimers and dendrons in the fields of functional materials and nanomedicines.     

Effect of stoichiometry on liquid crystalline supramolecular polymers formed with complementary nucleobase pair interactions

We report herein studies on the liquid crystalline behavior of a series of supramolecular materials that contain different ratios of two complementary symmetrically-substituted alkoxy-bis(phenylethynyl)benzene AA- and BB-type monomers. One monomer has thymine units placed at either end of the rigid mesogenic core, while the other has N⁶-(4-methoxybenzoyl)-adenine units placed on the ends. Differential scanning calorimetric and polarized optical microscopy studies have been carried out on these systems. These studies show that the material's behavior is strongly dependent on its thermal history. As a result, the materials can exhibit, on heating, either a liquid crystalline phase, a crystalline phase, or the coexistence of crystalline and liquid crystalline regions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5049–5059, 2006     

A glycoside of meristotropic acid

Chemistry of Natural Compounds -     

Architecture of a biocompatible supramolecular material by supersaturation-driven fabrication of its fiber network

The architecture of a biocompatible organogel formed by gelation of a small molecule organic gelator, N-lauroyl-L-glutamic acid di-n-butylamide, in isostearyl alcohol was investigated based on a supersaturation-driven crystallographic mismatch branching mechanism. By controlling the supersaturation of the system, the correlation length that determines the mesh size of the fiber network was finely tuned and the rheological properties of the gel were engineered. This approach is of considerable significance for many gel-based applications, such as controlled release of drugs that requires precise control of the mesh size. A direct cryo-transmission electron microscopy (TEM) imaging technique capable of preserving the network structure was used to visualize its nanostructure.     

Multifunctional compact zwitterionic ligands for preparing robust biocompatible semiconductor quantum dots and gold nanoparticles

We describe the synthesis of a series of four different ligands which are used to prepare hydrophilic, biocompatible luminescent quantum dots (QDs) and gold nanoparticles (AuNPs). Overall, the ligands are designed to be compact while still imparting a zwitterionic character to the NPs. Ligands are synthesized appended to a bidentate dihydrolipoic acid- (DHLA) anchor group, allowing for high-affinity NP attachment, and simultaneously incorporate tertiary amines along with carboxyl and/or hydroxyl groups. These are placed in close proximity within the ligand structure and their capacity for joint ionization imparts the requisite zwitterionic nature to the nanocrystal. QDs functionalized with the four different compact ligands were subjected to extensive physical characterization including surface charge, wettability, hydrodynamic size, and tolerance to a wide pH range or high salt concentration over time. The utility of the compact ligand coated QDs was further examined by testing of direct conjugation to polyhistidine-appended protein and peptides, aqueous covalent-coupling chemistry, and the ability to engage in F?rster resonance energy transfer (FRET). Conjugating cell penetrating peptides to the compact ligand coated QD series facilitated their rapid and efficient cellular uptake, while subsequent cytotoxicity tests showed no apparent decreases in cell viability. In vivo biocompatibility was also demonstrated by microinjecting the compact ligand coated QDs into cells and monitoring their stability over time. Inherent benefits of the ligand design could be extended beyond QDs as AuNPs functionalized with the same compact ligand series showed similar colloidal properties. The strong potential of these ligands to expand NP capabilities in many biological applications is highlighted.     

Acutifoliside,a novel benzoic acid glycoside from Salix acutifolia

Ultra high-performance liquid chromatography–mass spectrometry (UHPLC–MS) profiling of a polar solvent extract of juvenile stem tissue of Salix acutifolia Willd. identified a range of phenolic metabolites. Salicortin, 1, a well-known salicinoid, was the major compound present and the study identified young stem tissue of this species as a potential source of this compound for future studies. Three further known metabolites (salicin 2, catechin 3 and tremuloidin 4) were also present. The UHPLC–MS analysis also revealed the presence of a further, less polar, unknown compound, which was isolated via HPLC peak collection. The structure was elucidated by high-resolution mass spectroscopic analysis, 1- and 2-D NMR analysis and chemical derivatisation and was shown to be a novel benzoic acid glycoside 5, which we have named as acutifoliside.