Aggregation-induced Emission Fluorophore Research Articles

Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

A Dual Fluorescence Turn-On Sensor Array Formed by Poly(para-aryleneethynylene) and Aggregation-Induced Emission Fluorophores for Sensitive Multiplexed Bacterial Recognition.

Bacterial infections have emerged as the leading causes of mortality and morbidity worldwide. Herein, we developed a dual-channel fluorescence "turn-on" sensor array, comprising six electrostatic complexes formed from one negatively charged poly(para-aryleneethynylene) (PPE) and six positively charged aggregation-induced emission (AIE) fluorophores. The 6-element array enabled the simultaneous identification of 20 bacteria (OD600=0.005) within 30s (99.0 % accuracy), demonstrating significant advantages over the array constituted by the 7 separate elements that constitute the complexes. Meanwhile, the array realized different mixing ratios and quantitative detection of prevalent bacteria associated with urinary tract infection (UTI). It also excelled in distinguishing six simulated bacteria samples in artificial urine. Remarkably, the limit of detection for E. coli and E. faecalis was notably low, at 0.000295 and 0.000329 (OD600), respectively. Finally, optimized by diverse machine learning algorithms, the designed array achieved 96.7 % accuracy in differentiating UTI clinical samples from healthy individuals using a random forest model, demonstrating the great potential for medical diagnostic applications.

Design and synthesis of triphenylphosphine-based donor-π-acceptor fluorophores with strong aggregation-induced emission and enantiomer-paired flower-like stacking

Triphenylphosphine (TPP) shows stereo pyramidal configuration and has been considered as a poor electron-donor and fluorophore. Here, seven TPP-based compounds (o-TPPs 3a–3e and p-TPPs 3f/g) introducing simple non-aromatic electron-withdrawing (EW) groups at the ortho- and para-position of P atom have been synthesized to understand the inherent optical properties of TPP. All TPPs show aggregation-induced emission (AIE): non-emissive in solutions but emissive upon aggregation. Unexpectedly, lower conjugative o-TPPs possess much higher fluorescence quantum yields (43 and 65 %) than those (1 and 29 %) of their corresponding position isomers, p-TPPs; these achiral pyramidal TPPs in crystals exist as racemic M- and P-enantiomers, with all o-TPPs showing unique MP-paired flower-like arrangements; and the pyramidal TPP moiety could form an excellent electron delocalization system via through-space conjugation. This work proves that TPP could act as an excellent electron-donor and AIEgen by reasonable design, opens a new window to the application of pyramidal TPPs or other pyramidal compounds and affords a new strategy to design strong AIE fluorophores.

A novel polymer-based probe for fluorescently ratiometric sensing of hydrogen sulfide with multiple applications

Hydrogen sulfide (H2S) as an endogenous signaling molecule, plays an irreplaceable role in many important physiological activities. It is also closely related to sewage treatment, wine quality evaluation, and food spoilage. Herein, we have successfully synthesized a novel polymer-based probe P1 for fluorescently ratiometric sensing of H2S with a high selectivity and sensitivity. By virtue of ring-opening metathesis polymerization (ROMP), P1 was prepared with the disulfide bond linked coumarin-norbornene dyad NB-SS-COU as energy donor, the aggregation-induced emission (AIE) fluorophore anchored norbornene NB-TPE as energy receptor, and the polyethylene glycol (PEG) attached norbornene NB-PEG as a hydrophilic chain. At the 400 nm excitation, P1 displays a bright red emission at 615 nm due to the efficient fluorescence resonance energy transfer (FRET) from energy donor COU to energy acceptor TPE. Upon addition of H2S, it shows strong COU-based blue emission at 473 nm for cleavage of the disulfide bond. We also constructed a smartphone sensing platform to conduct visual quantitative detection of H2S by calculating the B/R (blue/red) emission ratio values. Moreover, P1 can be successfully employed in evaluating the level fluctuations of endogenous and exogenous H2S in living cells, testing water samples/wine samples, and monitoring food freshness.

Furan‐modified thiadiazolo quinoxaline as an electron acceptor for constructing second near‐infrared aggregation‐induced emission fluorophores for beyond 1300 nm fluorescence/photoacoustic imaging and photothermal therapy

AbstractCreation of new fluorophores is important for understanding the structure–property relationship, by which the required optical properties are likely to be attained. Herein, through theory calculation, it is found that furan‐modified thiadiazolo quinoxaline acting as an electron acceptor can endow donor–acceptor–donor (D–A–D) type second near‐infrared (NIR‐II) fluorophores with longer emission wavelength than the other thiadiazolo quinoxaline‐based acceptors containing pyridine, pyrrole, thiophene, and phenyl groups, respectively. On the basis of this theoretical prediction, a D–A–D type NIR‐II fluorophore with 6,7‐di(furan‐2‐yl)‐[1,2,5]thiadiazolo[3,4‐g] quinoxaline (DFTQ) as the acceptor and dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) as the donor is designed and synthesized, and the aggregation‐induced emission (AIE) function is further achieved by introducing the AIE units of tetraphenylethylene (TPE) and triphenylamine (TPA), respectively, totally forming three NIR‐II fluorophores DFTQ–DTP, DFTQ–DTPE, and DFTQ–DTPA. For biological applications, the fluorophores are encapsulated by amphiphilic DSPE–PEG2000 to generate water‐dispersible nanoparticles (NPs). Almost the whole emission of each of the NPs falls into the NIR‐II spectral range, with part emission beyond 1300 nm. By using DFTQ–DTPA NPs as the contrast and photothermal therapy (PTT) agent, high‐resolution in vivo fluorescence imaging is achieved in the greater than 1300 nm window, and their good performance in photoacoustic imaging and high tumor PTT efficacy in tumor‐bearing mice are also demonstrated. Taken together, this work mainly provides a strong electron acceptor for constructing long‐emitting fluorophores, and by using the electron acceptor, a AIE fluorophore with desirable quantum yield (QY) and photothermal conversion efficienciy (PCE) is synthesized and demonstrated to be promising in fluorescence/photoacoustic imaging and PTT.

Effect of Polymer Composition on the Optical Properties of a New Aggregation-Induced Emission Fluorophore: A Combined Experimental and Computational Approach.

Nowadays, fluorophores with a tetraphenylethylene (TPE) core are considered interesting due to the aggregation-induced emission (AIE) behavior that enables their effective use in polymer films. We propose a novel TPE fluorophore (TPE-BPAN) bearing two dimethylamino push and a 4-biphenylacetonitrile pull moieties with the typical AIE characteristics in solution and in the solid state, as rationalized by DFT calculations. Five different host polymer matrices with different polarity have been selected: two homopolymers of poly(methylmethacrylate) (PMMA) and poly(cyclohexyl methacrylate) (PCHMA) and three copolymers at different compositions (P(MMA-co-CHMA) 75:25, 50:50, and 25:75 mol%). The less polar comonomer of CHMA appeared to enhance TPE-BPAN emission with the highest quantum yield (QY) of about 40% measured in P(MMA-co-CHMA) 75:25. Further reduction in polymer polarity lowered QY and decreased the film stability and adhesion to the glass surface. LSC performances were not significantly affected by the matrix's polarity and resulted in around one-third of the state-of-the-art due to the reduced QY of TPE-BPAN. The theoretical investigation based on density functional theory (DFT) calculations clarified the origin of the observed AIE and the role played by the environment in modulating the photophysical behavior.

Construction of Covalent Organic Cages with Aggregation‐Induced Emission Characteristics from Metallacages for Mimicking Light‐Harvesting Antenna

AbstractA series of covalent organic cages built from fluorophores capable of aggregation‐induced emission (AIE) were elegantly prepared through the reduction of preorganized M2(LA)3(LB)2‐type metallacages, simultaneously taking advantage of the synthetic accessibility and well‐defined shapes and sizes of metallacages, the good chemical stability of the covalent cages as well as the bright emission of AIE fluorophores. Moreover, the covalent cages could be further post‐synthetically modified into an amide‐functionalized cage with a higher quantum yield. Furthermore, these presented covalent cages proved to be good energy donors and were used to construct light‐harvesting systems employing Nile Red as an energy acceptor. These light‐harvesting systems displayed efficient energy transfer and relatively high antenna effect, which enabled their use as efficient photocatalysts for a dehalogenation reaction. This research provides a new avenue for the development of luminescent covalent cages for light‐harvesting and photocatalysis.

Solid AIE fluorophore molecule with specific response of amide functional group to detect gaseous phosgene

A new solid Aggregation-induced Emission (AIE) fluorophore molecule (Ind-CONH2) for specific response of gaseous phosgene based on the dehydration of primary amide to nitrile was designed. Specially, visible AIE color changes of Ind-CONH2 with phosgene could be observed directly from bright blue to greenish blue on a portable solid-state test-strip under a 365 nm ultraviolet (UV) lamp, which showed inverse color changes from colorless to bright blue in homogeneous acetonitrile solution due to intramolecular charge transfer (ICT) effect. LOD of Ind-CONH2 for phosgene in acetonitrile was 1.52 nM and that for gaseous phosgene was 0.16 ppm (response time was less than 10 s in acetonitrile and 3 min for gas), which had a good development prospect in detecting phosgene. Additionally, Ind-CONH2 was successfully used as an erasable fluorescent anti-counterfeiting ink.

Assembling aggregation‐induced emission with natural DNA to maximize donor/acceptor ratio for efficient light‐harvesting antennae

AbstractArranging dense donors around a single acceptor for the assembly of efficient light‐harvesting antennas is a long‐standing challenge due to the intractable aggregation‐caused quenching of dense donors. Herein, we designed a cationic aggregation‐induced emission (AIE) amphiphile to self‐assemble with natural DNA duplexes. As an efficient donor, the as‐prepared cationic AIE amphiphile could be densely attached to the phosphate groups of natural DNA duplexes by using the smaller cationic trimethylammonium. The long alkyl chain between the cationic trimethylammonium and the AIE fluorophore allowed for avoiding the insufficient binding caused by the steric hindrance of the AIE fluorophore, resulting in a remarkably high donor/acceptor ratio comparable to that of the widely developed custom DNA assemblies. The proposed self‐assembly strategy provided novel flexible avenues for the assembling of finely controlled and efficient light‐harvesting systems into natural DNA with little synthetic modifications and low cost.

A novel red-emitting aggregation-induced emission probe for determination of β-glucosidase activity

β-Glucosidase (β-Glu) is a ubiquitous enzyme which has multiple roles in medical diagnosis, food production, agriculture, etc. Existing β-Glu assays have limitations such as complex operation, long running time, and high background noise. Here we report a red-emissive probe TBPG for measuring the activity of β-Glu. The probe was synthesized through conjugating a β-Glu targeting glucoside to an aggregation-induced emission (AIE) fluorophore. In the presence of β-Glu, TBPG was hydrolyzed and exhibited a fluorescence turn-on process. The detection conditions including time, temperature, pH value, buffer, and probe concentration were optimized systematically. Afterwards, fluorescence titration was conducted showing an excellent linearity (R2 = 0.998), a wide linear dynamic range (0–5.0 U/mL), and a limit of detection as low as 0.6 U/L. The detection specificity and ion interference were evaluated by adding various biological species and ions to probe without or with β-Glu. Next, we demonstrate the applicability of probe TBPG in determining the β-Glu activity in living cells using confocal microscopy and flow cytometry. Finally, this newly established assay was applied to real soil samples. Comparable results were obtained as the commercial assay, manifesting its great potential in soil enzyme analysis.

Anion-Complexation-Induced Emission Based on Aggregation-Induced Emission Fluorophore

Aggregation-induced emission (AIE) materials have attracted increasing research interest in recent years due to their excellent fluorescence properties in an aggregated state. Concurrently, anion coordination interactions have played a key role in the development of supramolecular assemblies and sensors. In the past decade, investigations towards fluorescent materials or sensors based on AIE and anion coordination interactions are continuously being reported. In this minireview, we briefly summarize the burgeoning progress of AIE-based materials and sensors driven by anion coordination interactions. We believe that an increasing number of achievements in anion-coordination induced emission materials will appear in the near future and will demonstrate potential applications, including bio-imaging and bio-sensors.

Heteroaryl-Substituted Bis-Anils: Aggregation-Induced Emission (AIE) Derivatives with Tunable ESIPT Emission Color and pH Sensitivity.

The two-step synthesis, structural, and photophysical properties of a series of heteroaryl-substituted bis-anil derivatives presenting aggregation-induced emission (AIE) coupled with an excited-state intramolecular proton transfer (ESIPT) process is described. The fluorescence color of the aggregates can be fine tuned by changing the electronic nature of the peripheral substitution, leading to a wide range of emission wavelengths (from green to the near infra-red). Moreover, upon introduction of strong electron-withdrawing groups such as cyano (CN), a competition between ESIPT and deprotonation is observed leading to the emission of the anionic species at low water percentage. This observation led to the synthesis of an additional mixed AIE fluorophore, functionalized by methoxy groups on one side and cyano groups on the other side. Upon addition of water, this dye displays first anionic emission, followed by typical AIE/ESIPT red fluorescence upon formation of the aggregates. TD-DFT calculations on selected AIE dyes were performed to rationalize the nature of the emissive transitions in these derivatives.

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.