Aggregation-induced Emission Fluorophore Research Articles

Configuration-Induced Multichromism of Phenanthridine Derivatives: A Type of Versatile Fluorescent Probe for Microenvironmental Monitoring.

Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine-based fluorophores (i.e., B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163 nm, which results in organic fluorophore-based full-color piezochromism. Moreover, both B1 and F1 exhibit an aggregation-caused quenching (ACQ) behavior, while T1 is an aggregation-induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring.

Janus-Type AIE Fluorophores: Synthesis and Properties of π-Extended Coumarin-Bearing Triskelions.

Janus-type triskelion-shaped fluorophores comprising coumarins bearing various electron-donating substituents (1aad, 1add, 1ccd, and 1cdd) were successfully synthesized via an intramolecular Ullmann coupling. Density functional theory (DFT) calculations indicated that all the compounds presented two different molecular surfaces, similar to Janus-type molecules. The absorption and fluorescence spectra of asymmetrical derivatives 1aad, 1add, 1ccd, and 1cdd exhibited a bathochromic shift due to their narrow highest occupied molecular orbital (HOMO) -lowest unoccupied molecular orbital (LUMO) gap. Natural transition orbital (NTO) analysis indicated that the excited state orbital overlaps differ among the C3 symmetrical and asymmetrical dyes. These triskelion-shaped fluorophores were found to form molecular nanoaggregates in THF/H2O mixtures and demonstrated aggregation-induced emission (AIE) enhancement characteristics as a result of restricting their molecular inversion. These results indicate that Janus-type AIE fluorophores are potentially applicable as solid-state fluorescent chiral materials, which can be optimized by controlling their molecular rearrangement in the solid state.

A novel strategy for sensitive detection of thrombin via subtly integrated polypeptide substrate and aggregation-induced emission fluorophores in carotid artery thrombosis

Accurate monitoring thrombin played an important role in the diagnosis of carotid artery thrombosis. In this investigation, a novel strategy was designed by one-step process for sensitive and specific detection of thrombin via integrated 2-(4-bromophenyl)− 3-(4-(4-(diphenylamino)styryl) phenyl) fumaronitrile (TPABDFN) and polypeptide substrate. More concretely, TPABDFN was gathered and wrapped by the peculiar short chain polypeptide substrate (SPS) with the assistance of glutaric dialdehyde in water containing 10 % tetrahydrofuran (THF), possessing an “ON” state owing to the aggregation-induced emission (AIE) characteristics. In the present of thrombin, the TPABDFN-SPS could be specifically degraded, leading the “OFF” state by the specific hydrolysis of thrombin. Indeed, the fluorescence intensity of the TPABDFN-SPS would decline with the increasing concentrations of thrombin. The results demonstrated that this “turn-off” fluorescent complex had a linear response in the range of 1.56–200 ng mL−1 for thrombin with the detection limit of 0.42 ng mL−1. More fascinatingly, this strategy could further applied to monitor thrombin in the plasma sample, which displayed that the thrombin concentration in the plasma of carotid artery thrombosis (CAT) rats was higher than that in the sham group. Conceivably, the proposed strategy showed prospective promise in the detection of target proteases for the diagnose of certain disease.

Highly Efficient and para-Selective C-H Functionalization of Polystyrene Providing a Versatile Platform for Diverse Applications.

Postpolymerization modification of polystyrene (PS) can afford numerous value-added materials with different functions and applications, but it has been hampered by the lack of efficient methods. We report herein a highly efficient and para-selective conversion of the C-H bonds of the aromatic ring of PS into diverse functional groups using a combination of thianthrenation and thio-Suzuki-Miyaura coupling reaction. Notably, the thianthrenation efficiency of PS is as high as 99% and the degree of thianthrenation can be conveniently controlled using stoichiometric tuning of the amount of thianthrene-S-oxide added, resulting in 24-99 mol % thianthrenation. In the subsequent thio-Suzuki-Miyaura coupling reaction, 18 functionalized PS containing various functional groups (-CH2OH, -OMe, -SMe, -OTBS, -CH3, -NHBoc, -OCOMe, -CHO, -COMe, -Si(Me)3, etc.) were successfully prepared with a high degree of functionalization (64-99 mol %). The obtained functionalized PS can be readily converted into diverse functional materials, including solid-phase synthesis resins, aggregation-induced emission fluorophores, as well as ionomer binders and ion-exchange membranes for energy conversion devices. This method imparts diverse functionality onto PS with extremely high efficiency and selectivity, providing a versatile platform to transform existing commodity PS plastics into high-performance materials.

NIR-II and visible fluorescence hybrid imaging-guided surgery via aggregation-induced emission fluorophores cocktails.

Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

Aggregation-Induced Emission Fluorophore-Incorporated Curcumin-Based Ratiometric Nanoprobe for Hypochlorite Detection in Food Matrices.

The development of efficient, economic, reliable, and accurate monitoring of hypochlorite (ClO-) in food matrices is in great demand for food safety assessment, particularly during its massive use against the COVID-19 epidemic. Here, we prepared an aggregation-induced emission (AIE) fluorophore tetraphenylethylene (TPE)-incorporated curcumin-based hybrid ratiometric fluorescence nanoprobe (Curcumin/TPE@HyNPs) through amphiphilic phospholipid polymer-powered nanoprecipitation, which exhibited a fast, highly sensitive, and selective response to the residual ClO- in real food matrices. Because of the inner filter effect (IFE) from curcumin toward TPE inside the nanoprobe, the bright fluorescence of TPE aggregation at ∼437 nm was effectively quenched, along with an enhanced fluorescence of curcumin at ∼478 nm. Once there was a ClO- residue in food matrices, ClO- triggered the oxidation of o-methoxyphenol inside curcumin and led to the almost complete absorption collapse, thereby terminating curcumin fluorescence at ∼478 nm and the IFE process. Accordingly, the fluorescence of TPE at ∼437 nm was recovered. In this case, a ratiometric fluorescent response of Curcumin/TPE@HyNPs toward the residual ClO- in food matrices (e.g., milk) was proposed with a low detection limit of 0.353 μM and a rapid response time of 140.0 s. Notably, the phospholipid polymer as the protection layer effectively reduced/evaded the nonspecific binding of signal reporters inside the nanoprobe, facilitating it to directly monitor the residual ClO- in real food matrices. This work provided a novel approach to utilize the unconventional AIE luminophors for constructing the efficient and reliable early warning mechanisms toward various food contaminants.

Through-bond/space conjugated nonaromatic dihydrobenzoquinolines: Luminogens with simple synthesis method, strong aggregation-induced emission and emissive excimers

In recent years, AIE (aggregation-induced emission) fluorophores have attracted great interest owing to their advantages in wide areas and many AIE fluorophores have be designed by combing conventional fluorophores with AIEgens that exhibiting AIE attributes. However, only few efficient AIEgens were developed. Here, novel dihydrobenzoquinolines (h-DHBQs 4a−e and f-DHBQ 5a), a new kind of AIEgens with strong AIE, are reported. DHBQs were synthesized by a catalyst-free multi-component reaction (MCR) in good overall yield and their optical properties were investigated through steady-state and transient fluorescence spectra, single-crystal diffraction, calculated HOMOs and LUMOs. It was found that DHBQs have these characteristics: a) strong AIE, that is, their fluorescence quantum yields lower than 4.1% in solutions, but high to 90.5% in crystals; b) efficient through-bond and -space conjugated nonaromatic central heterocycle; c) radiative-process-favored but non-radiative-decay-prevented self-assemblies; d) emissive excimers; and e) easily tunable fluorescence color. This work affords a new kind of AIEgens with excellent optical properties in solids and a strategy to develop AIEgens by constructing nonaromatic heterocycle using simple MCRs.

Aggregation-induced emission: An emerging concept in brain science

As an emerging concept in brain science, aggregation-induced emission (AIE) has captivated much interest by virtue of the unique superiority of AIE fluorophores in terms of emission intensity, imaging resolution, biocompatibility and photosensitivity. This review mainly overviews the current state-of-art advances of AIE fluorophores achieving the superb performance in brain imaging and therapy, which facilitate deep tissue penetration, high contrast to autofluorescence and efficient blood-brain barrier (BBB) crossing by rational molecular design and functionalized strategies. We expect this review serve as a modest spur to push forward the blooming growth of research in this fertile field.

Design and fabrication of chitosan-based AIE active micelles for bioimaging and intelligent delivery of paclitaxel

In this study, cetyl 4-formylbenzoate alkyl and 4-(2-hydroxyethoxy) benzophenonesalicylaldazide modified biotinylated chitosan (CS-BT-HBS-CB) featured with aggregation-induced emission (AIE) characteristic, active tumor-targeting ability and pH-responsive drug release property was designed and synthesized. The polymer was fabricated by introducing hydrophobic segment, tumor targeting ligand, acid-sensitive bond and AIE fluorophore to the backbone of chitosan. Due to its amphiphilicity, the polymer could self-assemble into micelles and encapsulate paclitaxel (PTX) to form PTX-loaded CS-BT-HBS-CB micelles. The mean size of the micelles was 167 nm, which was beneficial to the EPR effect. Moreover, with the help of above functional groups, the micelles exhibited excellent AIE effect, triggered drug release behavior by acidic condition, selective internalization by MCF-7 cells and excellent cellular imaging capability. In vivo studies revealed that the PTX-loaded CS-BT-HBS-CB micelles could enhance the antitumor efficacy with low systemic toxicity. This micellar system would be a potential candidate for cancer therapy and bioimaging.

Smart Tetraphenylethene-Based Luminescent Metal-Organic Frameworks with Amide-Assisted Thermofluorochromics and Piezofluorochromics.

Luminescent metal–organic frameworks (MOFs) are appealing for the design of smart responsive materials, whereas aggregation‐induced emission (AIE) fluorophores with twisted molecular rotor structure provide exciting opportunities to construct MOFs with new topology and responsiveness. Herein, it is reported that elongating AIE rotor ligands can render the newly formed AIE MOF (ZnETTB) (ETTB = 4',4''',4''''',4'''''''‐(ethene‐1,1,2,2‐tetrayl)tetrakis(([1,1'‐biphenyl]‐3,5‐dicarboxylic acid))) with more elasticity, more control for intramolecular motion, and specific amide‐sensing capability. ZnETTB shows specific host–guest interaction with amide, where N,N‐diethylformamide (DEF), as an example, is anchored through C—H···O and C—H···π bonds with Zn cluster and ETTB8− ligand, respectively. DEF anchoring reduces both the distortion level and the intramolecular motions of ETTB8− ligand to lead a blueshifted and intensified emission for DEF ∈ ZnETTB. Moreover, amide anchoring also affords the DEF ∈ ZnETTB with the excellent thermofluorochromic behavior, and further increases the piezofluorochromic sensitivity at low‐pressure ranges on the basis of its elastic framework. This work is one of the rare examples of amide‐responsive smart materials, which shall shed new lights on design of smart MOFs with twisted AIE rotors for further sensing and detection applications.

Specific “light-up” sensor made easy: An aggregation induced emission monomer for molecular imprinting

Development of a specific “light-up” sensor for detection of psychoactive drug has been a great challenge in forensic analysis. To achieve this goal, an aggregation induced emission (AIE) functional monomer containing both phenylboronic group and double bond was synthesized for construction of molecularly imprinted polymers (MIPs) based fluorescent sensor. In this AIE-MIP sensor, the AIE fluorophore could vibrate freely in the absence of the target analyte (cathinone, CAT), while this vibration was restricted after the specific molecular recognition, leading to “light-up” character of the corresponding sensor. FT-IR and LC-MS characterizations proved the AIE monomer was successfully introduced onto AIE-MIPs. SEM analysis indicated the AIE-MIPs was ∼140 nm in diameter. Binding experiments indicated the AIE-MIPs owned high specificity towards CAT. Fluorescent studies confirmed that the “light-up” capability of the AIE-MIPs was highly selective. On this basis, the AIE-MIP sensor was applied in detecting CAT in forensic samples. The sensor reached a detection limit of 0.32 μmol L-1 and exhibited a linear range of 2–12 μmol L-1. Compared to previously reported MIPs based electrochemical sensors and fluorescent sensors for measurement of CAT drug and its analogue, the present AIE-MIP sensor showed much higher sensitivity. To the best of our knowledge, this is the first time that an AIE functional monomer was synthesized for molecular imprinting, and also the first “light-up” AIE-MIP sensor to be reported. We believe that this versatile design of the specific “light-up” sensor can be used as a general protocol for construction of advanced sensor in various fields.

An ESIPT-Dependent AIE Fluorophore Based on HBT Derivative: Substituent Positional Impact on Aggregated Luminescence and its Application for Hydrogen Peroxide Detection.

Aiming to develop the facile organic fluorophore possessing excited state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE), we designed and synthesized two isomers with different linkage site between hydroxyl of 2-(2-hydroxyphenyl) benzothiazole (HBT) and a benzothiazole substituent (para position refers to p-BHBT and ortho position refers to o-BHBT). Fluorescence emission properties of p-BHBT and o-BHBT in THF/water mixtures with different water volume fractions indicated an opposite luminescence in aggregates, in which p-BHBT showed an ESIPT-dependent AIE properties while o-BHBT displayed ESIPT effect and aggregation-caused quenching (ACQ) qualities. A possible mechanism for molecular actions to illustrate the aggregating luminescence alteration of these two isomers had been proposed and verified by theoretical and experimental studies. More importantly, Probe-1, generated from dual ESIPT-AIE fluorophore p-BHBT, was successfully used as a ratiometric fluorescent chemosensor for highly selective (above 15-fold over other ROS) and sensitive (69-fold fluorescence enhancement with 0.22 μM of detection limit) detection of hydrogen peroxide in aqueous solution and living cells, respectively.

H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

Aggregation-induced emission fluorophore doped phosphate glass: Toward light-emitting electrochemical cells

Light-emitting electrochemical cells (LECs) are an easy-to-fabricate electroluminescent device, which in its simplest manifestation comprises an electroluminescence organic fluorophore and electrolytes as the active layer sandwiched between two electrodes. The LEC exhibits poor operational stability, and the poor thermal stability of the electrolyte is a major cause of the instability. Because most of the electrolytes utilized in LEC are organic electrolytes (polymer and ionic liquids), the thermal stability is difficult to improve on a large scale. Therefore, in this work, we are devoted to preliminarily exploring the possibility of using an inorganic glass electrolyte for LEC application. Following this objective, organic fluorophore (π-extended phosphole sulfide 1) doped inorganic phosphate amorphous matrix was successfully synthesized using spark plasma sintering technology. The optical properties, microstructure, and electrochemical properties of the hybrid glass were investigated, respectively. The ionic conductivity of the glass host can reach 10−7 S/cm at room temperature, and the glass matrix contain aggregates of 1 of around 100 nm. Strong photoluminescence at 600 nm, characteristic of the organic fluorophore, was observed in the hybrid glass. The cyclic voltammetry performed on the hybrid glass shows a redox couple contribution of the organic fluorophore. The result suggests 1 can complete the exchange of electric charges in the inorganic glass electrolyte, which is one of the fingerprints of the transient phenomena of a LEC.

AIE-Based Fluorescent Triblock Copolymer Micelles for Simultaneous Drug Delivery and Intracellular Imaging.

Fluorescent drug delivery systems have received increasing attention in cancer therapy because they combine drug delivery and bioimaging into a single platform. For example, polymers with aggregation-induced emission (AIE) fluorophores, such as tetraphenylethylene (TPE), have emerged as an elegant choice for drug delivery/bioimaging applications. In this work, we report one-pot sequential organocatalytic ring-opening polymerization of ε-caprolactone (CL) and ethylene oxide (EO) using TPE-(OH)2 as a difunctional initiator, in the presence of a t-BuP2/TEB Lewis pair (catalyst), in THF at room temperature. Two well-defined triblock copolymers with inverse block sequences, TPE-(PCL-b-PEO)2 and TPE-(PEO-b-PCL)2, were synthesized by altering the sequential addition of CL and EO. The physicochemical properties, including hydrodynamic diameter, morphology, and AIE properties of the synthesized amphiphilic triblock copolymers were investigated in aqueous media. The block copolymer micelles were loaded with anticancer drugs doxorubicin and curcumin to serve as drug delivery vehicles. In vitro studies revealed the accelerated drug release at lower pH (5.5), which mimics the tumor microenvironment, different from the physiological pH (7.4). In vitro cytotoxicity studies demonstrated that the neat block copolymer micelles are biocompatible, while drug-loaded micelles exhibited a significant cytotoxic effect in cancer cells. Cellular uptake, examined by confocal laser scanning microscopy, showed that the block copolymer micelles were rapidly internalized by the cells with simultaneous emission of TPE fluorophore. These results suggest that these triblock copolymers can be utilized for intracellular bioimaging.

An Enzyme-Activatable Aggregation-Induced-Emission Probe: Intraoperative Pathological Fluorescent Diagnosis of Pancreatic Cancer via Specific Cathepsin E.

Pancreatic cancer (PC) is one of the most devastating malignant tumors. However, fluorescence probes for early clinical diagnosis of PC often encounter difficulties in accuracy and penetrability. In this work, an enzyme-activated aggregation-induced-emission (AIE) probe, QM-HSP-CPP, for high-contrast fluorescence diagnosis of PC is developed by monitoring specific overexpressed enzyme Cathepsin E (CTSE). The probe is composed of an AIE fluorophore QM-COOH (QM = quinoline-malononitrile), CTSE-triggered hydrophobic peptide (HSP), and hydrophilic biocompatible cell penetrating peptide (CPP). The CPP unit can well-modulate the molecular dispersion properties, giving initial fluorescence-off state in the aqueous biosystem, thus endowing high signal-to-noise ratio, and finally overcoming the poor targeting selectivity of traditional AIE probes. CPP can ensure cell/tissue penetrating ability, thus allowing on-site monitoring of endogenous CTSE in PC cells, tissues, and living animal models. When the QM-HSP-CPP probe is specifically cleaved by CTSE, it can generate AIE signals in situ with high-specificity and long-term tracking ability, and successfully achieve intraoperative diagnosis of human PC sections, tracking PC in heterotopic nude mice models. The CTSE-enzyme-triggered AIEgens' liberation strategy improves accuracy and addresses the penetration problem simultaneously, which can expand the database of multitudinous biocompatible AIE-active probes, especially for establishing intraoperative pathological fluorescent diagnosis.

Insights into Optical Probes Based on Aggregation‐Induced Emission: from Restriction of Intramolecular Motions to Dark State (Advanced Optical Materials 21/2021)

Recently, many efforts have been devoted to mechanism studies on the luminescence nature of aggregation-induced emission (AIE) fluorophores. In article number 2100832, to disclose the connotation of the restrictions of intramolecular motions (RIM) theory, Wenbin Zeng and co-workers systematically summarize the advances of luminescence quenching mechanisms for AIE molecules. These insights are of great significance for fundamental understanding of the character of optical molecules.

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

Cucurbit-Like Polymersomes with Aggregation-Induced Emission Properties Show Enzyme-Mediated Motility.

Polymersomes that incorporate aggregation-induced emission (AIE) moieties are attractive inherently fluorescent nanoparticles with biomedical application potential for cell/tissue imaging and tracking, as well as phototherapeutics. An intriguing feature that has not been explored yet is their ability to adopt a range of asymmetric morphologies. Structural asymmetry allows nanoparticles to be exploited as active (motile) systems. Here, we present the design and preparation of AIE fluorophore integrated (AIEgenic) cucurbit-shaped polymersome nanomotors with enzyme-powered motility. The cucurbit scaffold was constructed via morphology engineering of biodegradable fluorescent AIE-polymersomes, followed by functionalization with enzymatic machinery via a layer-by-layer (LBL) self-assembly process. Because of the enzyme-mediated decomposition of chemical fuel on the cucurbit-like nanomotor surface, enhanced directed motion was attained, when compared with the spherical counterparts. These cucurbit-shaped biodegradable AIE-nanomotors provide a promising platform for the development of active delivery systems with potential for biomedical applications.

Circularly Polarized Fluorescence Resonance Energy Transfer (C-FRET) for Efficient Chirality Transmission within an Intermolecular System.

The occurrence and transmission of chirality is a fascinating characteristic of nature. However, the intermolecular transmission efficiency of circularly polarized luminescence (CPL) remains challenging due to poor through-space energy transfer. We report a unique CPL transmission from inducing the achiral acceptor to emit CPL within a specific liquid crystal (LC)-based intermolecular system through a circularly polarized fluorescence resonance energy transfer (C-FRET), wherein the luminescent cholesteric LC is employed as the chirality donor, and rationally designed achiral long-wavelength aggregation-induced emission (AIE) fluorophore acts as the well-assembled acceptor. In contrast to photon-release-and-absorption, the chirality transmission channel of C-FRET is highly dependent upon the energy resonance in the highly intrinsic chiral assembly of cholesteric LC, as verified by deliberately separating the achiral acceptor from the chiral donor to keep it far beyond the resonance distance. This C-FRET mode provides a de novo strategy concept for high-level information processing for applications such as high-density data storage, combinatorial logic calculation, and multilevel data encryption and decryption.