Visualizing molecular weights differences in supramolecular polymers.

Issues of molecular weight determination have been central to the development of supramolecular polymer chemistry. Whereas relationships between concentration and optical features are established for well-behaved absorptive and emissive species, for most supramolecular polymeric systems no simple correlation exists between optical performance and number-average molecular weight (Mn). As such, the Mn of supramolecular polymers have to be inferred from various measurements. Herein, we report an anion-responsive supramolecular polymer [M1·Zn(OTf)2]n that exhibits monotonic changes in the fluorescence color as a function of Mn Based on theoretical estimates, the calculated average degree of polymerization (DPcal) increases from 16.9 to 84.5 as the monomer concentration increases from 0.08 mM to 2.00 mM. Meanwhile, the fluorescent colors of M1 + Zn(OTf)2 solutions were found to pass from green to yellow and to orange, corresponding to a red shift in the maximum emission band (λmax ). Therefore, a relationship between DPcal and λmax could be established. Additionally, the anion-responsive nature of the present system meant that the extent of supramolecular polymerization could be regulated by introducing anions, with the resulting change in Mn being readily monitored via changes in the fluorescent emission features.

A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. METHODS: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. RESULTS: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. CONCLUSIONS: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

Characterization by Gel Permeation Chromatography of the Molecular Weight of Supramolecular Polymers Generated by Forming Polyrotaxanes through the Introduction of External Stoppers.

Supramolecular polymers find wide applications across diverse domains, and the molecular weight exerts a critical influence on their applicability. Consequently, the measurement of molecular weight for supramolecular polymers assumes paramount significance. Gel Permeation Chromatography (GPC) requiring low-concentration condition is a common characterization employed for molecular weight determination, which is not suitable for supramolecular polymers possessing concentration-independence property. Here, to break this threshold, we synthesized M1 embodying dibenzo-24-crown-8 (DB24C8) moiety as well as dibenzylammonium salt (DBA) group, which was capable of self-assembling into supramolecular polymers terminated with aldehyde groups at its end. Upon the addition of (4- (1,2,2-Triphenylvinyl) phenyl) methylamine (TPE-NH2), supramolecular polymers underwent a transition into polyrotaxanes, for which it was led by the generation of imine bonds. By virtue of GPC, the molecular weight of polyrotaxanes was obtained, then it was available to gain the molecular weight of supramolecular polymers with the help of transformation efficiency.

Construction of Supramolecular Polymers and Covalent Polymers via the Same Monomers.

Nature owns the ability to construct structurally different polymers from the same monomers. While polymers can be classified as covalent polymers (CPs) and supramolecular polymers (SPs), it is still difficult to synthesize CPs and SPs using same monomers like nature do. Herein, M1 with two diazo salts on both the ends was designed. Additionally, hydroquinone was chosen to be M2 for the existence of two hydroxyl groups. When mixing at room temperature, M1 and M2 self-assembled to SPs via N…H hydrogen bonds. In another way, upon the exposure to ultraviolet irradiation when blending M1 with M2, CPs were fabricated in the presence of covalent bonds. The excellent thermal stability of CPs was determined by TGA and DSC, while the great corrosion resistance of covalent polymers was detected by acid or alkali immersion. In this way, constructing two kinds of polymers using the same monomers was successfully achieved. This shows tremendous potential in fields of polymer science, supramolecular chemistry, which would boom the development of polymers.

Application of Organic Gel on Skin Realized by Hydrogel/Organic Gel Adhesion.

Diversity in solvent selection bestows the organic gel with appealing characteristics embracing antidrying, anti-icing, and antifouling abilities. However, organic gel, subjected to the "toxic" inherent property of solvent, is not able to be manipulated on skin. Herein, introducing the hydrogel layer amid organic gel and skin is envisaged to realize application of organic gel on skin. Hydrogel, inserted as the medium layer, works for the coupling role between skin and organic gel, also avoids the direct contact of organic gel toward skin. First, hydrogel system composed of acrylic acid is fabricated, meanwhile organic gel is prepared employing 2-hydroxyethyl methacrylate, ethylene glycol (EG) as solvent. Organic gel is able to adhere to hydrogel by hydrogen bonding resulting from carboxyl groups of polyacrylic acid chains and hydroxyl groups occurring on 2-hydroxyethyl methacrylate or EG. Additionally, hydrogen bonding enables the hydrogel to be firmly attached to skin, thus organic gel/hydrogel/skin assembly is produced. The further application of organic gel is exploited by incorporating stimuli-responsive dyes including spiropyran and rhodamine derivative.

Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Solvent-free autocatalytic supramolecular polymerization.

Solvent-free chemical manufacturing is one of the awaited technologies for addressing an emergent issue of environmental pollution. Here, we report solvent-free autocatalytic supramolecular polymerization (SF-ASP), which provides an inhibition-free template-assisted catalytic organic transformation that takes great advantage of the fact that the product (template) undergoes a termination-free nucleation-elongation assembly (living supramolecular polymerization) under solvent-free conditions. SF-ASP allows for reductive cyclotetramerization of hydrogen-bonding phthalonitriles into the corresponding phthalocyanines in exceptionally high yields (>80%). SF-ASP requires the growing polymer to form hexagonally packed crystalline fibres, which possibly preorganize the phthalonitriles at their cross-sectional edges for their efficient transformation. With metal oleates, SF-ASP produces single-crystalline fibres of metallophthalocyanines again in exceptionally high yields, which grow in both directions without terminal coupling until the phthalonitrile precursors are completely consumed. By taking advantage of this living nature of polymerization, multistep SF-ASP without/with metal oleates allows for the precision synthesis of multi-block supramolecular copolymers.

Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development.

Genome-wide association studies (GWAS) have identified numerous risk loci for venous thromboembolism (VTE), but it is challenging to decipher the underlying mechanisms. We employed an integrative analytical pipeline to transform genetic associations to identify novel plasma proteins for VTE. Proteome-wide association studies (PWAS) were determined by functional summary-based imputation leveraging data from a genome-wide association analysis (14,429 VTE patients, 267,037 controls), blood proteomes (1348 cases), followed by Mendelian randomization, Bayesian colocalization, protein-protein interaction, and pathway enrichment analysis. Twenty genetically regulated circulating protein abundances (F2, F11, ABO, PLCG2, LRP4, PLEK, KLKB1, PROC, KNG1, THBS2, SERPINA1, RARRES2, CEL, GP6, SERPINE2, SERPINA10, OBP2B, EFEMP1, F5, and MSR1) were associated with VTE. Of these 13 proteins demonstrated Mendelian randomized correlations. Six proteins (F2, F11, PLEK, SERPINA1, RARRES2, and SERPINE2) had strong support in colocalization analysis. Utilizing multidimensional data, this study suggests PLEK, SERPINA1, and SERPINE2 as compelling proteins that may provide key hints for future research and possible diagnostic and therapeutic targets for VTE.

Muscle-Like Supramolecular Polymers with Dual Motion Patterns.

Benefiting from the features like polymeric linear structures, stimuli-responsiveness and dynamic adaptiveness, supramolecular polymers (SPs) are favored as exploiting muscle-like materials, allowing for imitating the muscle functions. However, a substantial part of these materials barely owned an unitary motion orientation while it was obviously known that muscle movements involved distinct orientations. Herein, M1 holding the structure of 44-membered macrocycle with two aldehyde groups was designed, meanwhile, M2 comprising of secondary ammonium ions, 3,5-di-tert-butylphenyl groups as well as the alkyl chains was fabricated, for which it could be assembled with M1 to generate SPs based on host-guest interactions from a large macrocycle and two secondary ammonium ions. SPs underwent vertical compression upon the addition of N2 H4 owing to the forming dynamic covalent bonds, notably, mechanically interlocked structures were also generated. Afterwards, the vertically compressed SPs experienced horizontal shrinkage when tetrabutylammonium chloride was contributed due to the destruction of host-guest interactions.

Pillar[5]arene-Based AIE Supramolecular Polymer Networks Exhibiting Various Fluorescence to Achieve Visible Surveillance.

Supramolecular polymer networks (SPNs) based on pillar[n]arene are widely studied and it is known that evolution from linear polymers to SPNs occurs as a progressive process, which is of importance to monitor the detailed morphology throughout the process. Yet, the current reports related to that distinction by employing fluorescence approach have realized confined success, it still remains a challenge to distinguish the various states visually. Herein, a fluorescent group of the pyrene benzohydrazonate-based (PBHZ-based) derivative is introduced into the pillar[5]arene based SPNs gained from host-guest recognition, enabling the visual monitoring during the formation of SPNs. The whole visual detection was based on the fluorescence color transition ranging from blue to green relying on the gradual aggregated PBHZ molecules upon the increasing cross-linking degree. Besides, the stimuli-responsiveness of this SPNs was confirmed that increasing the temperature or adding a reducing agent would reduce the cross-linking degree.

Hydrogel-Based Macroscopic Click Chemistry.

The click reaction has found good utility across various fields due to the characteristics of high efficiency, atom economy, simple and mild reaction conditions. Click chemistry is usually utilized for connecting components of microscopic level, while it is still unable for joining macroscopic building blocks. Materials consisting of macroscopic building blocks realize the flexible fabrication of three-dimensional structures at macroscopic level, exerting significance on parallel manufactures. In this work, we reported macroscopic click chemistry utilizing hydrogel as macroscopic building blocks. Hydrogels G1 and G2 were prepared by incorporating M1 (N,N'-dimethyl-1,2-ethanediamine) and P1 (alkyne functionalized polyethylene glycol) respectively, where polymer chains formed through diffusion-induced amino-yne click reaction entangled different hydrogel networks together. Additionally, chain-like aggregates and complicated 3D structures such as tetrahedron and quadrangular pyramid were constructed based on the adhesion of the hydrogel blocks. The approach enables us to find more possibilities in the delicate designation of 3D aggregations as well as large-scale manufacturing.

Functional Supramolecular Polymeric Networks: The Marriage of Covalent Polymers and Macrocycle-Based Host-Guest Interactions.

Covalent polymers connected by non-covalent interactions constitute a fascinating set of materials known as supramolecular polymer networks (SPNs). A key feature of SPNs is that the underlying covalent polymers endow the resulting self-assembled materials with features, such as structural and mechanical integrity, good processability, recyclability, stimuli-responsiveness, self-healing, and shape memory, that are not recapitulated in the case of classic covalent polymer systems. The unique nature of SPNs derives from the controlled marriage of traditional covalent polymers and macrocycle-based host-guest interactions. As a consequence, supramolecular polymeric networks have played important roles in a number of diverse fields, including polymer science, supramolecular chemistry, materials science, biomedical materials, and information storage technology. In this Review, we summarize advances made in the area of functional SPNs, with a focus on original literature reports appearing in the past five years. The treatment is organized according to the key macrocycle-based host-guest interactions used to produce various SPNs. The role of the underlying polymer backbones is also discussed.

Metal-Ligand Interactions and Oligo(p-phenylene vinylene) Derivatives Based Supramolecular Polymer Possessing Variable Fluorescence Colors.

Fluorescent supramolecular polymers combine the benefits of supramolecular polymers in terms of dynamic nature with the optoelectronic features of incorporated fluorophores. However, the majority of fluorescent supramolecular polymers can only exhibit a single fluorescent state, restricting their applications. Incorporating J-type dyes into supramolecular monomers is expected to impart supramolecular polymers with variable fluorescence colors, because the aggregation mode of J-type dyes is closely related to the formation of supramolecular polymers. Herein, the authors report a supramolecular polymer [M1·Zn(OTf)2 ]n , in which the monomer M1 contains a J-type dye, oligo(p-phenylene vinylene) derivative, and two terpyridine ends. The M1 + Zn(OTf)2 solutions exhibit fluorescence color changes varying from cyan to yellow-green in the monomer concentration ranging from 0.04 to 1.00 mm. Moreover, based on the outputs from laser scanning confocal microscopy, the fluorescence color transition during the formation of supramolecular polymers is intuitively proven. Additionally, considering the close relationship between the supramolecular polymer structure and the fluorescence color, the fluorescence color can be regulated by introducing tetraethylammonium hydroxide that can bind with Zn2+ competitively to break up the structure of the supramolecular polymer.

Water compatible supramolecular polymers: recent progress.

Water compatible supramolecular polymers (WCSPs) combine aqueous compatibility with the reversibility and environmental responsiveness of supramolecular polymers. WCSPs have seen application across a number of fields, including stimuli-responsive materials, healable materials, and drug delivery, and are attracting increasing attention from the design, synthesis, and materials perspectives. In this review, we summarize the chemistry of WCSPs from 2016 to mid-2021. For the sake of discussion, we divide WCSPs into five categories based on the core supramolecular approaches at play, namely hydrogen-bonding arrays, electrostatic interactions, large π-conjugated subunits, host-guest interactions, and peptide-based systems, respectively. We discuss both synthesis and polymer structure, as well as the underlying design expectations. The goal of this overview is to deepen our understanding of the strategies that have been exploited to prepare WCSPs, as well as their properties and uses. Thus, a section devoted to potential applications is included in this review.

AIEgen-Enabled Multicolor Visualization for the Formation of Supramolecular Polymer Networks.

Extensive reports on the use of supramolecular polymer networks (SPNs) in self-healing materials, controlled release system and degradable products have led more researchers to tap their potential owing to the unique properties. Yet, the attendant efforts in the visualization through conventional luminescence methods during the formation of SPNs have been met with limited success. Herein, we designed a special type of SPNs prepared by PPMU polymer chains containing pyrene benzohydrazonate (PBHZ) molecules as AIEgens for the multicolor visualization with naked eyes. The complete detection of the formation process of the networks relied on the PBHZ molecules with aggregation-induced ratiometric emission (AIRE) effect, which enabled the fluorescence of the polymer networks transits from blue to cyan, and then to green with the increasing crosslinking degree derived from the hydrogen bonds between 2-ureido-4-pyrimidone (UPy) units of the polymer chains. Additionally, we certificated the stimuli-responsiveness of the obtained SPNs, and the fluorescence change, as well as observing the morphology transition. The AIEgen-enabled multicolor visualization of the formation of SPNs may provide better understanding of the details of the crosslinking interactions in the microstructural evolution, giving more inspiration for the multifunctional products based on SPNs.

A Strategy Based on Aggregation-Induced Ratiometric Emission to Differentiate Molecular Weight of Supramolecular Polymers.

Molecular weight has an important bearing on the properties of supramolecular polymers. However, the intuitive differentiation of the molecular weight of supramolecular polymers remains challenging. Given this situation, establishing a reliable relationship between fluorescence properties and molecular weight may be a promising strategy. Herein, we prepared a supramolecular monomer M1 with aggregation-induced ratiometric emission characteristics. With the increasing M1 concentration (0.100-100 mM), the average degree of polymerization (DPDOSY ) rose from 1.00 to 293. Meanwhile, the color changed from dark blue to cyan, finally to yellow-green in the same concentration range. Hence, the intuitive relationship between DPDOSY and fluorescence colors was constructed, allowing the visual differentiation of molecular weight. Moreover, the fluorescence color could be regulated by introducing a competitive molecule to induce the depolymerization of supramolecular polymers.

Calix[4]pyrrole-based Crosslinked Polymer Networks for Highly Effective Iodine Adsorption from Water.

A series of calix[4]pyrrole-based crosslinked polymer networks designed for iodine capture is reported. These materials were prepared by Sonogashira coupling of α,α,α,α-tetra(4-alkynylphenyl)calix[4]pyrrole with bishalide building blocks with different electronic properties and molecular sizes. Despite their low Brunauer-Emmett-Teller surface areas, iodine vapor adsorption capacities of up to 3.38 g g-1 were seen, a finding ascribed to the presence of a large number of effective sorption sites including macrocyclic π-rich cavities, aryl units, and alkyne groups within the material. One particular system, C[4]P-BTP, was found to be highly effective at iodine capture from water (uptake capacity of 3.24 g g-1 from a concentrated aqueous KI/I2 solution at ambient temperature). Fast capture kinetics (kobs =7.814 g g-1 min-1 ) were seen. Flow-through adsorption experiments revealed that C[4]P-BTP is able to remove 93.2 % of iodine from an aqueous source phase at a flow rate of 1 mL min-1 .

Unlocking Chemically Encrypted Information Using Three Types of External Stimuli.

Encryption is critical to information security; however, existing chemical-based information encryption strategies are still in their infancy. We report here a new approach to chemical encryption involving a supramolecular gel QR (quick response) code with multiple encryption functions. Three color "turn-on" supramolecular polymer gels, G1-G3, were prepared that produce pink, purple, and yellow colors when subject to treatment with acetic acid vapor, UV light, and methanolic FeCl3, respectively. As the result of hydrogen-bonding interactions at the gel interfaces, the three gels can be assembled to produce gel G4. Engraving a QR code pattern onto G4 then gave gel G5. When one or two stimuli are applied to the individual pieces corresponding to the QR engraved versions of the gels G1-G3 making up G5, a complete scannable pattern is not displayed, and the stored information cannot be recognized. Only when three different stimuli are applied at the same time does G5 give a complete recognizable pattern allowing the stored information to be retrieved. This strategy was applied to the decryption-based opening of a coded lock.

Calix[4]pyrrole-Crosslinked Porous Polymeric Networks for the Removal of Micropollutants from Water.

Calix[4]pyrrole-based porous organic polymers (P1-P3) for removing organic micropollutants from water were prepared. A bowl-shaped α,α,α,α-tetraalkynyl calix[4]pyrrole and diketopyrrolopyrrole monomer were crosslinked via Sonogashira coupling to produce a 3D network polymer, P1. P1 proved too hydrophobic for use as an adsorbent and was converted to the corresponding neutral polymer P2 (containing carboxylic acid groups) and its anionic derivative P3 (containing carboxylate anion groups). Anionic P3 outperformed P2 in screening studies involving a variety of model organic micropollutants of different charge, hydrophilicity and functionality. P3 proved particularly effective for cationic micropollutants. The theoretical maximum adsorption capacity (qmax,e ) of P3 reached 454 mg g-1 for the dye methylene blue, 344 mg g-1 for the pesticide paraquat, and 495 mg g-1 for diquat. These uptake values are significantly higher than those of most synthetic adsorbent materials reported to date.

Soft Materials Constructed Using Calix[4]pyrrole- and "Texas-Sized" Box-Based Anion Receptors.

Soft materials have received considerable attention from supramolecular chemists and material scientists alike. This interest reflects the advantages provided by their soft, flexible nature and the convenience of the molecular self-assembly that underlies their preparation. Common soft supramolecular materials include polymeric gels, supramolecular polymers, nanoaggregates, and membranes. Polymeric gels are solidlike networks of cross-linked polymer chains. Supramolecular polymers contain repeat units connected through reversible non-covalent bonds. Nanoaggregates are formed as a result of hydrophobic interactions involving amphiphilic building blocks. Because of the presence of non-covalent interactions, supramolecular soft materials typically display stimuli-responsive or adaptive features. Various macrocyclic hosts, such as cyclodextrins, crown ethers, calixarenes, cucurbiturils, and pillararenes, and many classic non-covalent interactions have been harnessed to construct supramolecular soft materials. Only recently has anion binding been used as the underlying recognition motif. Anions are ubiquitous in the natural world. Their importance has inspired efforts to achieve good anion binding and to exploit anion recognition in a number of fields, including extraction, transport, sensing, and catalysis. Most of this effort has involved the use of stand-alone anion receptors. On the other hand, soft materials with anion recognition features could lead to new macromolecular systems of interest in the context of many application areas. In this Account, we summarize the latest efforts from our laboratory to prepare supramolecular soft materials, including polymeric gels, supramolecular polymers, and nanoaggregates, with bona fide anion recognition features. Two anion receptor systems, namely, calix[4]pyrroles (C4Ps) and a tetraimidazolium macrocycle known as the "Texas-sized" molecular box (TxSB), have been used for this purpose. To date, TxSB-based hydrogels have been utilized to capture anions from water and for coded information applications; C4P-based organic polymeric gels have been used to extract dianions from aqueous source phases and for the on-site detection of chloride anions. Polymers containing C4P and TxSB anion recognition subunits typically display responsive features and can be modified through application of appropriately chosen external stimuli. For instance, nanoaggregates may be formed as a result of the hydrophobic interactions of C4P- and TxSB-based amphiphiles. The resulting aggregates were found to mimic the structural evolution of organelles and could be used as effective anion and ion pair extractants. This Account summarizes progress to date while underscoring potential opportunities associated with combining anion recognition and soft materials chemistry. The hope is to stimulate further advances in broad areas, including polymer science, supramolecular chemistry, biology, materials research, and information storage.