Heteroatom-Promoted Polyhexagonal Saddle-Shaped Molecular Structures and their Supramolecular Coassembly with C60.

Molecules with curved architecture can exhibit unique optoelectronic properties due to the concave-convex π-surface. However, synthesizing negatively curved saddle-shaped aromatic systems has been challenging due to the internal structural strain. Herein, we report the facile synthesis of two polyhexagonal molecular systems, 1 and 2, with saddle shape geometry by judiciously varying the aromatic moiety, avoiding the harsh synthetic methods as that of heptagonal aromatic saddle systems. The unique geometry preferences of B, N, and S furnish suitable curvature to the molecules, featuring saddle shape. The saddle geometry also enables them to interact with fullerene C60 , and the supramolecular interactions of fullerene C60 with 1 and 2 modify their optoelectronic properties. Crystal structure analysis reveals that 1, with a small π-surface, forms a double columnar array of fullerenes in the solid state. In contrast, 2 with a large π-surface produces a supramolecular capsule entrapping two discrete fullerenes. The intermolecular interactions between B, N, S, and the aryl-π surface of the host and C60 guest are the stabilizing factors for creating these supramolecular structures. Comprehensive computational, optical, and Raman spectroscopic studies establish the charge transfer interactions between B-N doped heterocycle host and fullerene C60 guest.

Homochiral and Heterochiral Self-Sorting Assemblies of Antiaromatic Ni(II) Norcorrole Dimers.

Recently, π-π stacked antiaromatic π-systems have received considerable attention because they can exhibit stacked-ring aromaticity due to substantial intermolecular orbital interactions. Here, we report three antiaromatic norcorrole dimers that self-assemble to form supramolecular architectures through chiral self-sorting. A 2,2'-linked norcorrole dimer with 3,5-di-tert-butylphenyl groups forms a π-stacked dimer both in solid and solution states via homochiral self-sorting. Its association constant in solution is (3.6±1.7)×105 M-1 at 20 °C. In the solid state, 3,3'-linked norcorrole dimers with 3,5-di-tert-butylphenyl and phenyl groups afford macrocyclic and helical supramolecular assemblies via heterochiral and homochiral self-sorting, respectively. Notably, the subtle modification in the substituent resulted in a complete change in the structure of the aggregates and the chiral self-sorting mode. The present findings demonstrate that structural manipulation in antiaromatic monomer units leads to the formation of various supramolecular assemblies on the basis of the attractive interactions between antiaromatic π-systems.

Controlling Chirogenic Effects in Porphyrin Based Supramolecular Systems: Theoretical Analysis Versus Experimental Observations.

Electronic circular dichroism (ECD) spectroscopy is a widely employed method for studying chiral analysis, requiring the presence of a chromophore close to a chiral centre. Porphyrinoids are found to be one of the best chromophoric systems serving for this purpose and enabling the application of ECD spectroscopy for chirality determination across diverse classes of organic compounds. Consequently, it is crucial to understand the induction mechanisms of ECD in the porphyrin-based complexes. The present study explores systematically the influence of secondary chromophores, bonded to an achiral zinc porphyrin or to chiral guest molecules, on the B-region of ECD spectra using the time-dependent density functional theory (TD-DFT) calculations. The study analyses the impact of change in both the conformation of achiral porphyrin (host) and change in position and conformation of chiral organic molecule (guest) on the B-band of ECD spectra (energy, intensity, sign of Cotton effect). Finally, conclusions made on model complexes are applied to published experimental data, contributing to a deeper understanding of various factors influencing ECD spectra in chiral systems. In addition, a computer program aimed to help rationalise ECD spectra by visualizing corresponding orbital energies, rotatory strengths, electric and magnetic transition moments, and angles between them, is presented.

Amino-Acid Based Chiral Trisubstituted Benzimidazole Supramolecules: Synthesis and Self-Assembling Behavior.

Trisubstituted 1,3,5-tri(benzimidazolyl)benzene derivatives were synthesized from l-alanine, l-valine, d-valine and glycine, and their self-assembling behavior and stimuli-response in solution and gel states were evaluated. Circular dichroism/UV-vis absorption spectroscopic and dynamic light scattering measurements revealed that the compounds formed H-aggregates via intramolecular hydrogen bonding and π-π stacking interactions in nonpolar solvents such as CHCl3, whereas collapse of the aggregates was confirmed by MeOH addition. Quantum mechanical calculations and molecular dynamics simulations also supported aggregation in CHCl3 . Rheological analysis and morphology observation revealed the formation of a fibril like structure by further assembling of aggregates at a high concentration in CHCl3 .

[Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond].

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Cyclization of an Achiral Flipping Panel to Homochiral Tubes Exhibiting Circularly Polarized Luminescence.

Macrocyclization of the bendable 2,7-dimethoxythianthrene with methylene linkages afforded a pair of homochiral macrocycles featuring a hex-nut-like geometry. Their structures were fully characterized by NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction analysis. Their stable planar chirality facilitates efficient resolution of the pair of enantiomers which could be readily derivatized. Installing phenylethynyl groups on their rims leads to luminescent tubular macrocycles exhibiting circularly polarized luminescence with a large dissymmetry value |glum | of 5×10-3 . Supramolecular binding of electron-deficient guests by the tube results in fluorescence quenching, which proved its potential for the future development of switchable chiroptical systems.

Biomimetic lipidic nanovectors for effective asparaginase supramolecule delivery.

Effectiveness of enzyme therapy is limited by enzyme drawbacks such as short half-life, low bioavailability and high immunogenicity. We loaded asparaginase (Aase) into hydroxypropyl- or sulfonbutylether-beta cyclodextrin to form supramolecular amphiphilic molecules by self-assembly followed by entrapment inside the cores of two biomimetic lipidic nanovectors (AS-XLNs). Supramolecular structure was simulated by molecular docking. AS-XLNs maintained superior activity through isolating Aase from external environment due to docking with cyclodextrin and coating with biomimetic membrane. Fluorescent probes and computational simulations were used to reveal possible interactions between serum albumin/trypsin and Aase/nanovector membrane components which were partly responsible for enhanced bioavailability and bioactivity of AS-XLNs compared to Aase. AS-XLNs significantly increased cytotoxicity against pulmonary tumor cells due to synergistic effects of Aase and nanovector membrane components (killing tumor cells through apoptosis induced by asparagine depletion and autophagy inhibition or via targets such as vascular endothelial growth factor A, alpha-amylase, p-selectin or androgen receptor).

Supramolecule self-assembly synthesis of amyloid phenylalanine-Cu fibrils with laccase-like activity and their application for dopamine determination.

Laccases are multicopper proteins for dioxygen-involved oxidation of a broad spectrum of organic compounds. I Novel amyloid-like phenylalanine-Cu (F-Cu(II)) fibrils were developed, which were obtained via supramolecular self-assembly of Cu2+ and phenylalanine (F) under basic condition. The obtained amyloid-like fibrils represented highly periodic structure, of which the lattice unit was constructed via alternating hydrophobic (aromatic environment) and hydrophilic (both hydrogen bonding and Cu(II) coordination) interactions. Relative to natural laccases, the amyloid-like F-Cu(II) architecture exhibited comparable substrate affinity (Michaelis constant, Km = 0.75 mM) and higher catalytic efficiency (kcat/Km = 773.33 × 10-3 g-1 min-1L). Moreover, it exhibited remarkable tolerances in pH (4 ~ 10), temperature (room temperature ~ 200 ℃), organic solvent, and long-term storage (> 15 days). These stabilities were superior among the reported nature and artificial laccases, presenting a more promising candidate in various chemo- or bio-applications. In addition, F-Cu(II) fibrils could catalyze the oxidation of dopamine (DA) to a brown product, in which a new absorption band at 470 nm was observed. Based on this, a simple colorimetric assay for the detection of DA could be performed. We reported a novel amyloid-like phenylalanine-Cu fibrils, in which F-Cu+ complex can mimick the T1 site of natural laccase to oxidize the substrates. Then electrons transferred to F-Cu2+ complex via N-H···O=C hydrogen binding pathway. Finally, the dioxygen was transformed to water though radical reaction.

A Bionic Nano-Band-Aid Constructed by the Three-Stage Self-Assembly of Peptides for Rapid Liver Hemostasis.

Critical challenges remain in trauma emergency and surgical procedures involving liver bleeding, particularly in perforating wounds that cannot be pressed and large wounds that cannot be sewn. Self-assembling peptide hydrogels are particularly attractive due to their intrinsic biocompatibility and programmability. Herein, we develop a nano-band-aid (NBA) through a three-stage self-assembly strategy of two functionalized peptides, which were first coassembled into nanofibers and then woven to a meshlike network driven by Ca2+. Then, catalyzed by blood coagulation factor XIIIa (FXIIIa), NBA underwent a third stage, self-assembly into a densely compacted physical barrier to stop and control the bleeding. As expected, NBA rapidly and efficiently stopped the bleeding in rat liver scratches while effectively reducing the inflammation around the wound and promoting the wound healing. This bionic self-assembly strategy will provide a clinically potential peptide-based treatment for fatal liver bleeding and reinvigorate efforts to develop self-assembling peptide hydrogels as hemostatic agents.

Charged Tubular Supramolecule Boosting Multivalent Interactions for the Drastic Suppression of Aß Fibrillation.

Anti-Aß therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD). However, suppressing Aß aggregation and disintegrating mature fibrils simultaneously remains a great challenge. In this work, we developed a new strategy using a charged tubular supramolecule (CTS) with pillar[5]arene as the backbone and modifying amino and carboxyl groups at the tubular terminals (noted as CTS-A, CTS-A/C, and CTS-C, respectively) to suppress Aß fibrillation for the first time. According to the spectroscopic and microscopic characterizations, Aß40 fibrillation can be efficiently suppressed by CTS-A in a very low inhibitor:peptide (I:P) molar ratio (1:10). A greatly alleviated cytotoxic effect of Aß peptides after the inhibition or disaggregation process is further disclosed. The well-organized supramolecular structure drives multivalent interaction and gains enhanced efficiency on amyloid fibrillar modulation. These results open a new path for the design of supramolecules in the application of AD treatment.

ß-Cyclodextrin-Based Supramolecular Imprinted Fiber Array for Highly Selective Detection of Parabens.

A novel high-throughput array analytical platform based on derived ß-cyclodextrin supramolecular imprinted polymer (SMIP) fibers was constructed to achieve selective enrichment and removal of parabens. SMIP fiber arrays have abundant imprinting sites and introduce the host−guest inclusion effect of the derived ß-cyclodextrin, which is beneficial to significantly improve the adsorption ability of fiber for parabens. Upon combination with HPLC, a specific and sensitive recognition method was developed with a low limit of detection (0.003−0.02 µg/L, S/N = 3) for parabens analysis in environmental water. This method has a good linearity (R > 0.9994) in the linear range of 0.01−200 µg/L. The proposed SMIP fiber array with high-throughput adsorption capacity has great potential in monitoring water pollution, which also provides a reliable reference for the analysis of more categories of pharmaceutical and personal care product pollutants.

A Review of Crystalline Multibridged Cyclophane Cages: Synthesis, Their Conformational Behavior, and Properties.

This paper reviews the most stable conformation of crystalline three-dimensional cyclophane (CP) achieved by self-assembling based on changing the type of aromatic compound or regulating the type and number of bridging groups. [3n]cyclophanes (CPs) were reported to form supramolecular compounds with bind organic, inorganic anions, or neutral molecules selectively. [3n]cyclophanes ([3n]CPs) have stronger donor capability relative to compound [2n]cyclophanes ([2n]CPs), and it is expected to be a new type of electron donor for the progress of fresh electron conductive materials. The synthesis, conformational behavior, and properties of crystalline multi-bridge rings are summarized and discussed.

[Material basis of Rhei Radix et Rhizoma-Coptidis Rhizoma combination in alleviating "bitter-cold" properties based on supramolecular chemistry of Chinese medicine].

The present study aimed to explore the material basis of Rhei Radix et Rhizoma-Coptidis Rhizoma combination in alleviating "bitter-cold" properties based on the supramolecular chemistry of Chinese medicine.Dynamic light scattering and scanning/transmission electron microscopy were used to characterize the morphological characteristics of supramolecules in the decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma.The chemical composition of supramolecules, as well as the dissolution and release processes of supramolecules and the medicinal components of Coptidis Rhizoma decoction, was determined by the high-performance liquid chromatography-mass spectrometry.The differences in "bitter-cold" medicinal properties between Rhei Radix et Rhizoma decoction, Coptidis Rhizoma decoction, and co-decoction were analyzed by sensory evaluation, electronic tongue, mouse diarrhea model, and pathological indicators.The anthraquinones/tannins and alkaloids interacted to form supramolecules with a scale of about 400 nm when Rhei Radix et Rhizoma and Coptidis Rhizoma were decocted together, which delayed the dissolution and release of the active components represented by berberine. Compared with the consequence of single drug administration at 4 g·kg~(-1), the combination of the two drugs at 8 g·kg~(-1) significantly alleviated the "bitter-cold" properties.The effective components interacted to form supramolecules in the co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma, which affected the dissolution and release of the effective components of Chinese medicinal decoction, thereby alleviating the "bitter-cold" properties.The findings of this study provide a new idea for revealing the scientific compatibility of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Design of a Metallacycle-Based Supramolecular Photosensitizer for In Vivo Image-Guided Photodynamic Inactivation of Bacteria.

Bacterial infection is one of the greatest threats to public health. In vivo real-time monitoring and effective treatment of infected sites through non-invasive techniques, remain a challenge. Herein, we designed a PtII metallacycle-based supramolecular photosensitizer through the host-guest interaction between a pillar[5]arene-modified metallacycle and 1-butyl-4-[4-(diphenylamino)styryl]pyridinium. Leveraging the aggregation-induced emission supramolecular photosensitizer, we improved fluorescence performance and antimicrobial photodynamic inactivation. In vivo studies revealed that it displayed precise fluorescence tracking of S. aureus-infected sites, and in situ performed image-guided efficient PDI of S. aureus without noticeable side effects. These results demonstrated that metallacycle combined with host-guest chemistry could provide a paradigm for the development of powerful photosensitizers for biomedicine.

Stoichiometry between Humate Unit Molecules and Metal Ions in Supramolecular Assembly Induced by Cu2+ and Tb3+ Measured by Gel Electrophoresis Techniques.

Humic acid (HA), a fraction of humic substances, can strongly complex with metal ions to form a supramolecular assembly via coordination binding and other intermolecular forces. However, determining the supramolecular size distribution and stoichiometry between small HA unit molecules constituting HA supramolecules and metal ions has proven to be challenging. Here, we investigated the changes in the size distributions of HAs induced by Cu2+ and Tb3+ ions using unique PAGE for the separation and quantification of HA complexes and metal ions bound, followed by UV-vis spectroscopy and excitation-emission matrix-parallel factor analysis. By determining the concentrations of HA and metal ions, it was possible to estimate the stoichiometry of the HA unit molecule to metal ions in supramolecular complexes. It was found that the supramolecular behaviors of Cu2+ and Tb3+ complexes with HA collected from peat (PAHA) and deep groundwater (HHA) differed. For example, two HHA unit molecules form a supramolecule via cross-linking by a Cu2+ ion in the case of Cu2+-HHA. Our results suggest that this supramolecular stoichiometry is related to the abundance of sulfur atoms in the elemental composition of HHA. Our experimental results and analysis provide new insights into HA supramolecules formed via metal complexation.

Synthesis of Azacalixarenes and Development of Their Properties.

This review focuses on the synthesis, structure, and interactions of metal ions, the detection of some weak interactions using the structure, and the construction of supramolecules of azacalixarenes that have been reported to date. Azacalixarenes are characterized by the presence of shallow or deep cavities, the simultaneous presence of a basic nitrogen atom and an acidic phenolic hydroxyl group, and the ability to introduce various side chains into the cyclic skeleton. These molecules can be given many functions by substituting groups on the benzene ring, modifying phenolic hydroxyl groups, and converting side chains. The author discusses the evidence of azacalixarene utilizing these characteristics.

A Highly Selective Supramolecule Array Membrane Made of Zero-Dimensional Molecules for Gas Separation.

We orderly assembled zero-dimensional 2-methylimidazole (mim) molecules into unprecedented supramolecule array membranes (SAMs) through solvent-free vapor processing, realizing the intermolecular spacing of mim at ca. 0.30 nm available as size-sieving channels for distinguishing the tiny difference between H2 (kinetic diameter: 0.289 nm) and CO2 (kinetic diameter: 0.33 nm). The highly oriented and dense membranes yield a separation factor above 3600 for equimolar H2 /CO2 mixtures, which is one order of magnitude higher than those of the state-of-the-art membranes defining 2017's upper bound for H2 /CO2 separation. These SAMs define a new benchmark for molecular sieve membranes and are of paramount importance to precombustion carbon capture. Given the range of supramolecules, we anticipate SAMs with variable intermolecular channels could be applied in diversified separations that are prevalent in chemical processes.

Stepwise Self-Assembly and Dynamic Exchange of Supramolecular Snowflakes.

Snowflake, a highly symmetrical hexagram figure, is challenging to be expressed by chemistry/supramolecular chemistry due to the complex structure. Herein, we have constructed super snowflake supramolecules using terpyridine (tpy)-based metal-organic building blocks with and connectivities through stepwise strategies in high yield. The structures were characterized by multi-dimensional mass spectrometry and multi-dimensional NMR spectrometry. In order to address the stability/tolerance of our designed super snowflake structures, ligand exchange behaviors between different supramolecules with various arm length were fully investigated by mass spectrometry. The study revealed that three modes could exist in such binary systems, including full exchange, partial exchange and self-sorting (no exchange) depending on the length difference of ligands.

Synthesis and characterization of triazole based supramolecule for interaction with cefuroxime in tap water and blood plasma.

In this study a new calix[4]arene triazole 5 was successfully synthesized using click reaction and characterized through UV-visible, FT-IR, 1H NMR spectroscopes and Mass Spectrometry. The supramolecular interaction of compound 5 towards commonly used drugs has been carried out using UV-Visible spectroscopy. The supramolecule 5 showed characteristic enhancement in the absorbance intensity after mixing with Cefuroxime at pH (2-12). Compound 5 displayed considerably good interactions with cefuroxime in the presence of other drugs. Compound 5 exhibits linear relationship with cefuroxime concentration in the range of (10-80µM) with regression value of 0.9954. The standard deviation for 50µM Cefuroxime was found to be 0.01 and the limit of detection for cefuroxime was calculated to be 2µM. Job's plot experiments showed 1:1 (5: cefuroxime) binding stoichiometry between compound 5 and cefuroxime. Supramolecule 5 displayed fairly good spectrophotometric recognition of Cefuroxime in human blood plasma and tap water thus showing that the ingredients of tap water and plasma sample was inert in the recognition of cefuroxime.

Nanotubes of Biomimetic Supramolecules Constructed by Synthetic Metal Chlorophyll Derivatives.

Various supramolecular nanotubes have recently been built up by lipids, peptides, and other organic molecules. Major light-harvesting (LH) antenna systems in a filamentous anoxygenic phototroph, Chloroflexus (Cfl.) aurantiacus, are called chlorosomes and contain photofunctional single-wall supramolecular nanotubes with approximately 5 nm in their diameter. Chlorosomal supramolecular nanotubes of Cfl. aurantiacus are constructed by a large amount of bacteriochlorophyll(BChl)-c molecules. Such a pigment self-assembles in a chlorosome without any assistance from the peptides, which is in sharp contrast to the other natural photosynthetic LH antennas. To mimic chlorosomal supramolecular nanotubes, synthetic models were prepared by the modification of naturally occurring chlorophyll(Chl)-a molecule. Metal complexes (magnesium, zinc, and cadmium) of the Chl derivative were synthesized as models of natural chlorosomal BChls. These metal Chl derivatives self-assembled in hydrophobic environments, and their supramolecules were analyzed by spectroscopic and microscopic techniques. Cryo-transmission electron microscopic images showed that the zinc and cadmium Chl derivatives could form single-wall supramolecular nanotubes and their outer and inner diameters were approximately 5 and 3 nm, respectively. Atomic force microscopic images suggested that the magnesium Chl derivative formed similar nanotubes to those of the corresponding zinc and cadmium complexes. Three chlorosomal single-wall supramolecular nanotubes of the metal Chl derivatives were prepared in the solid state and would be useful as photofunctional materials.