Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens

Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of operation.The purpose of this study was to explore whether aggregation-induced emission luminogens(AIEgens)can be used for highly specific imaging of MSU crystals to assist in the diagnosis of gout.First,we developed a series of luminogens(i.e.,tetraphenyl ethylene(TPE)-NH_(2),TPE-2NH_(2),TPE-4NH_(2),TPE-COOH,TPE-2COOH,TPE-4COOH,and TPE-Ketoalkyne),each of which was then evenly mixed with MSU crystals.Next,optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope(CLSM).This approach was used for imaging standard samples of MSU,hydroxyapatite(HAP)crystals,and mixed samples with 1:1 mass ratio of MSU/HAP.We also imaged samples from mouse models of acute gouty arthritis,HAP deposition disease,and comorbidities of interest.Subsequently,CLSM imaging results were compared with those of compensated polarized light microscopy,and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell line.Finally,CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and tophi.As a promising candidate for MSU crystal labeling,TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples,animal samples,and human samples,and could precisely distinguish gout from HAP deposition disease.This work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases.

Understanding the role of interconnecting layer on determining monolithic perovskite/organic tandem device carrier recombination properties

As one of the core parts of two-terminal(2 T) monolithic tandem photovoltaics, the interconnecting layers(ICLs) play a critical role in modulating the carrier transport and recombination between the sub-cells,and thus influencing the tandem device performance. Here, for the first time, the relationship between ICLs architecture and 2 T monolithic perovskite/organic tandem device performance has been studied by investigating the change of ICLs composition layer thickness on the ICLs optical and electrical properties, sub-cells EQE properties, and tandem device J-V properties. It is revealed that the ability of ICLs on modulating the sub-cells carrier balance properties is strongly associated with its composited layers thickness, and the tandem device carrier balance properties can be reflected by the relative EQE intensity between the sub-cells. Finally, with a deep understanding of the mechanisms, rational design of ICLs can be made to benefit the tandem device development. Based on the optimized ICL a high PCE of 20.03% is achieved.

Visualization of supramolecular assembly by aggregation-induced emission

Supramolecular architectures are constructed by the self-assembly of small building blocks via the use of metal-ligand coordination,π–πstacking interactions,hydrogen bonding,host-guest interactions,and other noncovalent driving forces,which confer unique dynamic reversibility and stimulus responsiveness to the supramolecular materials and also lead to the demand of expensive and complex equipment for the characterization of supramolecular assembly processes.Fortunately,the self-assembly processes bring the monomeric chromophores together,offering possibilities to establish ties between the supramolecular assembly and aggregation-induced emission(AIE)techniques.Compared to conventional luminescent molecules,AIE luminogens(AIEgens)exhibit significant fluorescence enhancement upon the restriction of molecular motions,thus displaying the advantages of signal amplification and low background noises.Given the above,the real-time,sensitive,and in situ visualization of the formation of self-assemblies and their stimuli responsiveness based on AIE becomes accessible.Here,we review recent works that encompass the visualization of supramolecular assembly-related behaviors by means of AIE characteristics of chromophores.The organization of this review will be by different types of supramolecular architectures,including metallacycles/cages,micelles/vesicles,supramolecular polymers,and supramolecular gels.An overview of future opportunities and challenges for the real-time monitoring of supramolecular assembly by AIE is also provided.

A multifunctional nanoaggregate-based system for detection of rheumatoid arthritis via Optoacoustic/NIR-Ⅱ fluorescent imaging and therapy via inhibiting JAK-STAT/NF-κB/NLRP3 pathways

Rheumatoid arthritis(RA)is a debilitating autoimmune disease that causes chronic pain and serious complications,presenting a significant challenge to treat.Promising approaches for treating RA involve signaling pathways modulation and targeted therapy.To this end,a multifunctional nanosystem,TPC-U@HAT,has been designed for RA therapy,featuring multitargeting,dual-stimuli response,and on-demand drug release capabilities.TPC-U@HAT is composed of a probe/prodrug TPC,a JAK1 kinase inhibitor upadacitinib,and the drug carrier HAT.TPC is composed of an aggregation-induced emission(AIE)-active NIR-II chromophore TPY and an NF-κB/NLRP3 inhibitor caffeic acid phenethyl ester(CAPE),connected via boronic ester bond which serves as the reactive-oxygen-species-responsive linker.The carrier,HAT,is created by grafting bone-targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains,which can encapsulate TPC and upadacitinib to form TPC-U@HAT.Upon intravenous injection into mice,TPC-U@HAT accumulates at inflamed lesions of RA through both active and passive targeting,and the overexpressed hyaluronidase and H_(2)O_(2) therein cleave the hyaluronic acid polymer chains and boronate bonds,respectively.This generates an AIE-active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR-II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF-κB/NLRP3 and JAK-STAT pathways.

Electrosynthesis of Azobenzenes Directly from Nitrobenzenes

The electrochemical reduction strategy of nitrobenzenes is developed.The chemistry occurs under ambient conditions.The protocol uses inert electrodes and the solvent,DMSO,plays a dual role as a reducing agent.Its synthetic value has been demonstrated by the highly efficient synthesis of symmetric,unsymmetric and cyclic azo compounds.

Functional Hyperbranched Polythioamides Synthesized from Catalyst-free Multicomponent Polymerization of Elemental Sulfur

Hyperbranched polymers with unique topological structures,large number of branching sites and terminal groups have attracted much attention,and are expected to possess advanced functionalities compared with their linear polymer counterparts.The devel-opment of hyperbranched polymers is hence highly desired but challenging,especially for sulfur-containing polymers which are at-tractive metal absorbents,optical materials,dielectric materials,and self-healing materials.In this work,six hyperbranched polythi-oamides with various topological structures,well-defined repeating units,satisfying yields(up to 99%),and high molecular weights(up to 101400 g/mol)were successfully designed and synthesized from the catalyst-free multicomponent polymerization of ele-mental sulfur,aromatic alkynes and aliphatic amines,through different monomer combination strategies based on the designed three-or four-functional alkyne and amine monomers.The hyperbranched polythioamides possess unique luminescence property,and strong affinity toward Hg^(2+),which can be utilized in the fluorescence detection of Hg^(2+),as well as mercury removal from aque-ous solutions with high efficiency of 99.99%and low mercury residue of 0.1 ppb.Hyperbranched polythioamides with unique struc-tures may be developed to a group of fascinating materials and find their potential applications as metal absorbents and optoelec-tronic materials.

White-light emission from organic aggregates:a review

White light,which contains polychromic visible components,affects the rhythm of organisms and has the potential for advanced applications of lighting,display,and communication.Compared with traditional incandescent bulbs and inorganic diodes,pure organic materials are superior in terms of better compatibility,flexibility,structural diversity,and environmental friendliness.In the past few years,polychromic emission has been obtained based on organic aggregates,which provides a platform to achieve white-light emission.Several white-light emitters are sporadically reported,but the underlying mechanistic picture is still not fully established.Based on these considerations,we will focus on the single-component and multicomponent strategies to achieve efficient white-light emission from pure organic aggregates.Thereinto,single-component strategy is introduced from four parts:dual fluorescence,fluorescence and phosphorescence,dual phosphorescence with anti-Kasha’s behavior,and clusteroluminescence.Meanwhile,doping,supramolecular assembly,and cocrystallization are summarized as strategies for multicomponent systems.Beyond the construction strategies of white-light emitters,their advanced representative applications,such as organic light-emitting diodes,white luminescent dyes,circularly polarized luminescence,and encryption,are also prospected.It is expected that this review will draw a comprehensive picture of white-light emission from organic aggregates as well as their emerging applications.

Manipulation of clusteroluminescence in carbonyl-based aliphatic polymers

Clusteroluminogens(CLgens),nonconjugated structures with visible luminescence at the clustering state,have recently received remarkable attention due to their great theoretical significance and practical values.In carbonyl-based aliphatic polymers,(n,π*)transition of carbonyl groups and the through-space interactions have been demonstrated to play an important role in their clusteroluminescence(CL)properties,but it is still a big challenge to manipulate their CL at the molecular level.In this work,six nonconjugated carbonyl-based polymers with different heteroatoms and steric hindrances were synthesized,and their photophysical properties were systematically studied.These polymers all showed CL but with different emission efficiency and wavelength.Experimental and theoretical studies indicated that the CL properties could be manipulated by changing the electronic structures of carbonyl groups and the rigidity of polymer chains.This work not only gains further insights into the CL mechanism but also provides reliable strategies to design and manipulate non-conjugated luminescent materials.

Metal-Free Synthesis of Benzo[a]phenanthridines from Aromatic Aldehydes,Cyclohexanones,and Aromatic Amines

A three-component synthesis of benzo[a]phenanthridines from aromatic aldehydes,cyclohexanones,and aromatic amines has been developed,which is mediated by KI/DMSO/camphorsulfonic acid to afford a variety of functionalized benzo[a]phenanthridines in satisfactory yields.The present strategy provides a biaryl motif ortho to the nitrogen atom which has the potential to be used as ligand by further modification.With the advantages of readily available starting materials,transition-metal-free conditions,gram-scale synthesis,and broad substrate scope,this three-component protocol provides an efficient approach for the preparation of diverse benzo[a]phenanthridines.

Functional Polyselenoureas for Selective Gold Recovery Prepared from Catalyst-Free Multicomponent Polymerizations of Elemental Selenium

Selenium-containing polymers with fascinating functionalities such as stimuli-responsive property,enzyme mimics,antioxidant activity,promotion of immune-cell activity,anticancer activity,and controlled delivery property,are highly desired,but rarely developed due to their underexplored synthetic methods.Herein,through careful design of monomeric structures and polymerization conditions,we report a series of catalyst-free multicomponent polymerizations(MCPs)of elemental selenium with aliphatic/aromatic diamines and diisocyanides that directly converted selenium to polyselenoureas with long-term stability,good solubility,well-characterized structures,and unique functionalities.The MCPs enjoyed broad monomer scope and fast conversion in 1 min,delivering 18 polyselenoureas with high molecular weights(M_(w)s up to 94,600 g/mol)in high yields(up to 99%).Furthermore,the polyselenoureas could be used for the extraction of Au^(3+)from mixed-metal ion solutions under practical conditions with high selectivity,sensitivity(<1μg/L),efficiency(>99.99%),and capacity(up to 665.60 mg·Au^(3+)/g)within 1 min.Further,the elemental gold was recoverable after the pyrolysis of the polymer complexes.

Adaptive Chirality of an Achiral Cage:Chirality Transfer,Induction,and Circularly Polarized Luminescence through Aqueous Host-Guest Complexation

Chirality transfer,induction,and circularly polarized luminescence(CPL)using supramolecular hosts,such as macrocycles and cages,have been explored for wide-ranging applicationsin chiral recognition,sensing,catalysis,and chiroptical functional materials.Herein,we report the adaptive chirality of an achiral tetraphenylethene(TPE)-basedoctacationic cage(1)inducedby bindingwith enantiopure deoxynucleotides(A,T,C,and G)throughhost-guest(H-G)complexationinwater.The hydrophobic cavity of the cage efficiently stabilizes the hydrogen-bonded dimerization of deoxynucleotides(A_(2),T_(2),C_(2),and G_(2))to form H-G complexes in 1∶2 ratios.Given the photophysical properties and dynamic rotational conformation of the TPE units of the cage,cage⊃deoxynucleotide complexes exhibited excellent chiroptical propertiesbased on chirality transfer andinduction from the chiral guest to the achiral host.For this supramolecular system,the cage showed a unique adaptive chirality of the double clockwise-typed(PP)rotational conformation of the two TPE units,which was induced by chiral guests(e.g.,A_(2),T_(2),C_(2),and G_(2))through H-G complexation in water.Furthermore,the adaptive chirality of the cage⊃deoxynucleotide complexes successfully induced CPL signals in homogeneous aqueous solutions.This study provides insights for the construction of adaptive chirality from an achiral TPE-based octacationic cage with dynamic conformational nature,and might facilitate further design of chiral functional materials for several applications,such as chiral recognition,sensing,displays,catalysis,and other chiral fluorescent supramolecular systems based on aqueous H-G complexation.

Diamines,CS2 and Monoisocyanide-participated Polymerizations for Large-scale Synthesis of Polythioureas and Thioformamide

Multicomponent polymerizations(MCPs)are powerful tools to synthesize functional polymers with great structural diversity,low cost and high efficiency,which usually generate single polymer product.Herein,a robust one-pot diamines,CS_(2)and monoisocyanide-participated catalyst-free polymerization was developed at room temperature to produce polythiourea and thioformamide simultaneously in equal equivalent,which was featured with cheap monomers,simple operation and mild condition,affording various polythioureas with high Mws of up to 4.75×10^(4)g/mol in high yields of up to 98%.Polythioureas with varied chain composition and sequence-controlled structure could be synthesized in 62 g-scale from copolymerization or multicomponent tandem polymerization,enabling facile tuning of thermal property,crystallinity,mechanical property,and fluorescence.The abundant irregular hydrogen bonds endowed the polythioureas excellent glassy state self-healing property at room temperature or below 0℃.This polymerization provided an efficient and economic approach to access functional polythioureas.

The commercial antibiotics with inherent AIE feature: In situ visualization of antibiotic metabolism and specifically differentiation of bacterial species and broad-spectrum therapy

The research on pharmacology usually focuses on the structure-activity relationships of drugs,such as antibiotics,to enhance their activity,but often ignores their optical properties.However,investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism.In this work,we identified a class of commercialized antibiotics,such as levofloxacin,norfloxacin,and moxifloxacin(MXF)hydrochloride,featuring the unique aggregation-induced emission(AIE)characteristics.By taking advantage of their AIE feature,antibiotic metabolism in cells could be in situ visualized,which clearly shows that the luminescent aggregates accumulate in the lysosomes.Moreover,after a structure-activity relationship study,we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared,which is able to specifically differentiate bacterial species after only 10 min of treatment.Moreover,MXF-P shows highly effective broad-spectrum antibacterial activity,excellent therapeutic effects and biosafety for S.aureus-infected wound recovery.Thus,this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.

A Versatile Tetraphenylethene Derivative Bearing Excitation Wavelength Dependent Emission,Multistate Mechanochromism,Reversible Photochromism,and Circularly Polarized Luminescence and Its Applications in Multimodal Anticounterfeiting

Multimodal anticounterfeiting has become increasingly challenging in modern society to guarantee information security and the safety of property.In this study,a versatile cholesterol-containing tetraphenylethene derivative is shown to have multiple optical properties,including stimuli-responsive fluorescence,reversible photochromism,excitation wavelength dependent luminescence,and circularly polarized luminescence.After the application of diverse processing methods(writing,screen painting,drawing,and pyrography),we found that this molecule can serve as an anticounterfeiting toolbox to provide rich anticounterfeiting effects through the synergistical use of multiple optical properties.This work offers important insight for designing novel small organic molecules for advanced multimodal anticounterfeiting technology.

Antifouling mechanism of natural product-based coatings investigated by digital holographic microscopy

Using natural product-based antifouling coatings has proven to be an effective strategy to combat biofouling.However,their antifouling mechanisms are still unclear.In this study,the antifouling mechanism of natural product-based coatings consisting of bio-sourced poly(lactic acid)-based polyurethane and ecofriendly antifoulant(butenolide)derived from marine bacteria was revealed by observing 3D bacterial motions utilizing a 3D tracking technique-digital holographic microscopy(DHM).As butenolide content increases,the density of planktonic marine bacteria(Pseudomonas sp.)near the surface decreases and thus leads to a reduced adhesion,indicating that butenolide elicits the adaptive response of Pseudomonas sp.to escape from the surface.Meanwhile,among these remained cells,an increased percentage is found to undergo subdiffusive motions compared with the case of smaller dose of butenolide.Further experiments show that butenolide can accelerate their swimming velocity and reduce flick frequency.Antibacterial assay confirms that butenolide-based coating shows high efficacy of antifouling performance against Pseudomonas sp.but without killing them like 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one(DCOIT).

A specific aggregation-induced emission-conjugated polymer enables visual monitoring of osteogenic differentiation

Osteogenic differentiation is the basis of bone growth and repair related to many diseases,in which evaluating the degree and ability of osteogenic transformation is quite important and highly desirable.However,fixing or stopping the growth of cells is required for conventional methods to monitor osteogenic differentiation,which cannot realize the full investigation of the dynamic process.Herein,a new anion conjugated polymer featuring aggregation-induced emission(AIE)characteristics is developed with excellent solubility for in-situ monitoring the process of osteogenic differentiation.This novel polymer can bind with osteogenic differentiated cells,and the intracellular fluorescence increases gradually with the enhancement of osteogenic differentiation.Moreover,it possesses good biosafety with negligible effect on cell activity and osteogenic differentiation,which cannot be realized by the typical method of Alizarin Red S staining.Further study shows that the polymer crosses the cell membrane through endocytosis and enriches in lysosomes,whereas no obvious fluorescence is detected with other cells,including non-differentiated osteoblast cells,under the same conditions,demonstrating the high selectivity.This is the first fluorescent probe with excellent specificity to realize real-time observation of the process of osteogenic differentiation.Therefore,PTB-EDTA shows great promise in the study of osteogenic differentiation and related applications.

Ultralong organic room-temperature phosphorescence of electrondonating and commercially available host and guest molecules through efficient Förster resonance energy transfer

Ultralong organic room-temperature phosphorescence(RTP)materials have attracted tremendous attention recently due to their diverse applications.Several ultralong organic RTP materials mimicking the host-guest architecture of inorganic systems have been exploited successfully.However,complicated synthesis and high expenditure are still inevitable in these studies.Herein,we develop a series of novel host-guest organic phosphorescence systems,in which all luminophores are electron-rich,commercially available and halogen-atom-free.The maximum phosphorescence efficiency and the longest lifetime could reach 23.6%and 362 ms,respectively.Experimental results and theoretical calculation indicate that the host molecules not only play a vital role in providing a rigid environment to suppress non-radiative decay of the guest,but also show a synergistic effect to the guest through Förster resonance energy transfer(FRET).The commercial availability,facile preparation and unique properties also make these new host-guest materials an excellent candidate for the anti-counterfeiting application.This work will inspire researchers to develop new RTP systems with different wavelengths from commercially available luminophores.

Red AIE conjugated polyelectrolytes for long-term tracing and image-guided photodynamic therapy of tumors

Robust photosensitizers with strong red/NIR fluorescence, efficient reactive oxygen species(ROS) generation and high photostability are highly desired for photodynamic therapy(PDT). Herein, three novel red conjugated polyelectrolytes(CPEs) with tetraphenylethene and 2,1,3-benzothiadiazole on the main chains and triphenylphosphonium on the side chains are developed.These CPEs display apparent aggregation-induced emission feature and high fluorescence quantum yields in the aggregated state. They can target lysosome in He La cells for fluorescence bioimaging. By virtue of the good retention effect and high photostability, these CPEs show ultralong-term tracing performance of subcutaneous tumors, and the tumor site can still be visualized for 20 days after injection. Owing to their good biocompatibility and strong ROS generation ability, the image-guided PDT based on these CPEs can effectively inhibit the growth of subcutaneous tumor and significantly prolong the survival of tumor bearing mice. The H&E and IHC staining reveal that the PDT of these CPEs depress the proliferation of tumor cells, and promote apoptosis and necrosis process. These new CPEs may be employed both as fluorescent probes for in vitro and in vivo long-term tracing and as photosensitizers for image-guided PDT of tumors.

Green Monomer of CO_(2) and Alkyne-based Four-component Tandem Polymerization toward Regio-and Stereoregular Poly(aminoacrylate)s

Green monomers, such as carbon dioxide(CO_(2)), are closely related to our daily life and highly desirable to be transferred to functional polymers with diverse structures and versatile properties because they are abundant, cheap, nontoxic, renewable, and sustainable. However, the polymerizations based on these green monomers are to be further developed. In this work, a facile CO_(2) and alkyne-based one-pot, two-step, fourcomponent tandem polymerization was successfully established. The polymerization of CO_(2), diynes, alkyl dihalides, and primary/secondary amines can proceed under mild reaction conditions and regio-and stereoregular poly(aminoacrylate)s with good solubility and thermal stability were obtained in high yields(up to 95%). Notably, distinctly different stereoregularity of resultant poly(aminoacrylate)s was realized via using primary or secondary amines. Using the former would readily generate polymers with 100% Z-isomers, whereas the latter furnished products with over 95% E-isomers. Through different monomer combination, the polymers with tunable structures and properties were obtained.Moreover, the tetraphenylethene units containing poly(aminoacrylate)s, showing the unique aggregation-induced emission characteristics,could function as a fluorescent probe for sensitive explosive detection. Thus, this work not only develops a facile CO_(2) and alkyne-based multicomponent tandem polymerization but also provides a valuable strategy to fine-tune the polymer structures and properties, which could be potentially applied in diverse areas.

Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways

Immune-mediated inflammatory diseases(IMIDs)represent a diverse group of diseases and challenges remain for the current medications.Herein,we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways.A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate(EGCG)through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety.BH-EGCG molecules readily form stable nanoparticles in aqueous medium,which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites.Additionally,an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy.Benefiting from the inflammation-homing effect of the macrophage membrane,the nanosystem delivers payloads(diagnostic probe and therapeutic drugs)to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS,thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models,including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation.This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.