AIE Fluorophore Research Articles

Triplex DNA-based aggregation-induced emission probe: A new platform for hybridization chain reaction-based fluorescence sensing assay

The hybridization chain reaction (HCR), as one of the nucleic acid amplification technologies, is combined with fluorescence signal output with excellent sensitivity, simplicity, and stability. However, current HCR-based fluorescence sensing methods still have some defects such as the blocking effect of the HCR combination with fluorophores and the aggregation-caused quenching (ACQ) phenomenon of traditional fluorophores. Herein, a triplex DNA-based aggregation-induced emission probe (AIE-P) was designed as the fluorescent signal transduction, which is able to provide a new platform for HCR-based sensing assay. The AIE-P was synthesized by attaching the AIE fluorophores to terminus of the oligonucleotide through amido bond, and captured the products of HCR to form triplex DNA. In this case, the AIE fluorophores were located in close proximity to generate fluorescence. This assay provided turn-on fluorescence efficiency with a high signal-to-noise ratio and excellent amplification capability to solve the shortcoming of HCR-based fluorescence sensing methods. It enabled sensitive detection of Vibrio parahaemolyticus in the range of 102–106 CFU mL−1, and with a low limit of detection down to 39 CFU mL−1. In addition, this assay expressed good specificity and practicability. The triplex DNA-based AIE probe forms a universal molecular tool for developing HCR-based fluorescence sensing methods.

AIEgen-caged ultrafast photochemical delivery and visualization of nitric oxide

The development of bifunctional AIEgens for direct delivering and visualizing bioactive species together remains a great challenge to date. Herein, we fabricated a novel photoactivatable nitric oxide (NO) donor with a built-in AIE fluorophore, which can rapidly release NO and AIEgen upon light irradiation. The ultrafast NO generation can be obtained in 2.1 ps, with the yielding of a greatly drastic fluorescence turn-on AIEgen probe (300,000-fold intensity enhanced). Using this NO donor, real-time cell images of NO-releasing through the emission of AIEgen were successfully achieved through direct excitation of the donor in cells in situ.

A chalcone-based ESIPT and AIE fluorophore for β-gal imaging in living cells.

β-Galactosidase (β-gal), which is responsible for the hydrolysis of the glycosidic bond of lactose to galactose, has been recognized as an important biomarker of cell or organism status, especially cell senescence and primary ovarian cancer. Extensive efforts have been devoted to develop probes for detecting and visualizing β-gal in cells. Herein, a fluorescent probe gal-HCA which possesses both excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) properties was prepared to monitor β-gal in living cells. The probe consists of 2-hydroxy-4'-dimethylamino-chalcone (HCA) capped with a D-galactose group. The cleavage of the glycosidic bond in gal-HCA triggered by β-gal releases HCA, which results in a significant bathochromic shift in fluorescence from 532 to 615 nm. The probe exhibited high selectivity and sensitivity toward β-gal with a detection limit as low as 0.0122 U mL-1. The confocal imaging investigation demonstrated the potential of gal-HCA in monitoring the endocellular overexpressed β-gal in senescent cells and ovarian cancer cells. This study provides a straightforward approach for the development of fluorescent probes to monitor β-gal and detection of β-gal-associated diseases.

Jellyfish-inspired smart tetraphenylethene lipids with unique AIE fluorescence, thermal response, and cell membrane interaction.

Smart lipids with fluorescence emission, thermal response, and polyethylene glycolation (PEGylation) functions can be highly valuable for formulation, image-traceable delivery, and targeted release of payloads. Herein, a series of jellyfish-shaped amphiphiles with a tetraphenylethene (TPE) core and four symmetrical amphiphilic side chains were conveniently synthesized and systematically investigated as smart lipids. Compared with regular amphiphilic TPE lipids and phospholipids, the unprecedented jellyfish-shaped molecular geometry was found to enable a series of valuable capabilities, including sensitive and responsive aggregation-induced emission of fluorescence (AIE FL) and real-time FL monitoring of drug uptake. Furthermore, the jellyfish-shaped geometry facilitated the concentration-dependent aggregation from unimolecular micelles at low concentrations to "side-by-side" spherical aggregates at high concentrations and a unique mode of AIE. In addition, the size and the arrangement of the amphiphilic side chains were found to dominate the aggregate stability, cell uptake, and thus the cytotoxicity of the amphiphiles. This study has unprecedentedly developed versatile smart TPE lipids with precise structures, and unique physicochemical and biological properties while the peculiar structure-property relationship may shed new light on the design and application of AIE fluorophores and functional lipids in biomedicine and materials science.

Silver metallization-triggered liposome-embedded AIE fluorophore for dual-mode detection of biogenic amines to fight food freshness fraud.

To combat food freshness fraud, it is urgent to develop a method which could realize the detection of biogenic amines (BAs) present in food. In our study, we developed a colorimetric and ratiometric fluorescence dual-mode sensor which integrated with silver metallization-based response system of AIE liposome+OPD+RSM+Ag+ toward BAs in foods for fighting freshness fraud. With the hydrolysis from the alkaline of BAs to resorcinol monoacetate (RSM), the production resorcinol (RS) could metallize silver ion (Ag+) to silver atoms (Ag0) which could lead to a BAs concentration-dependent decrease of the oxidation product 2,3-diaminophenothiazine (DAP) of Ag+ to o-phenylenediamine (OPD). As a result, the dual-mode sensor has a low detection limit and wide linear range in the spiked detection of soy products, pork and milk samples for BAs. Thus, providing a reliable method for food safety and forestalling food freshness fraud.

Mitochondrial-Targeted AIE-Active Fluorescent Probe Based on Tetraphenylethylene Fluorophore with Dual Positive Charge Recognition Sites for Monitoring ATP in Cells.

Adenosine triphosphate (ATP), as an important intracellular energy currency produced in mitochondria, is closely related to various diseases in living organisms. Currently, the biological application of AIE fluorophore as a fluorescent probe for ATP detection in mitochondria is rarely reported. Herein, D-π-A and D-A structure-based tetraphenylethylene (TPE) fluorophores were employed to synthesize six different ATP probes (P1-P6), and the phenylboronic acid groups and dual positive charge sites of probes could interact with the vicinal diol of ribose and negatively charged triphosphate structure of ATP, respectively. However, P1 and P4 with a boronic acid group and a positive charge site had poor selectivity for ATP detection. In contrast, P2, P3, P5, and P6 with dual positive charge sites exhibited better selectivity than P1 and P4. In particular, P2 had more advantages of high sensitivity, selectivity, and good time stability for ATP detection than P3, P5, and P6, which was ascribed to its D-π-A structure, linker 1 (1,4-bis(bromomethyl)benzene), and dual positive charge recognition sites. Then, P2 was employed to detect ATP, and it exhibited a low detection limit of 3.62 μM. Moreover, P2 showed utility in the monitoring of mitochondrial ATP level fluctuations.

Efficient single benzene AIE system: Optical waveguide and invisible ink

The construction of novel aggregation-induced emission luminogens (AIEgens) is beneficial for the derivation of new organic materials and exploration of potential application of AIEgens. Herein, a symmetrical AIE single-benzene derivative MeDHQB which contains two aliphatic rings without typical aromatic rotors of propeller-like AIEgens was designed. Two crystal forms were discovered by controlling the crystallization conditions. It was found that the aliphatic rings weaken the structural rigidity and promote the molecular vibration, which drastically increase the nonradiative transition in solution and can be inhibited in the aggregate states. Meanwhile, the dissimilar polymorphic physicochemical properties of MeDHQB-I and MeDHQB-II were investigated by experimental and theoretical methods. Additionally, the thermal transformation from MeDHQB-I to MeDHQB-II and the potential applications of optical waveguide and invisible ink were carefully discussed. Results presented in this work provide an efficient strategy for the construction of multifunctional AIE fluorophore based on compact single-benzene system.

AIE-active phenothiazine based Schiff-base for the selective sensing of the explosive picric acid in real water samples and paper-based device

A highly selective and sensitive AIE fluorescent chemosensor based on phenothiazine and ethylene diamine was synthesized (DPTZ-SB) for the exclusive detection of picric acid (PA). Interestingly, DPTZ-SB can sense PA exclusively over five other competitive explosives, due to the specific complexation ability of DPTZ-SB towards PA. For the better mechanistic understanding, Stern-Volmer, Modified Stern-Volmer and Job’s plot were employed, which showed the limit of detection and binding constant to be 0.2 ppb and 4.05 × 1010 M−1, respectively, and the stoichiometric ratio of DPTZ-SB:PA as 1:2. The values are promising as compared to the AIE fluorophores reported for PA sensing recently. The sensing mechanism was elucidated using DFT studies and 1H NMR titration experiment, which revealed the active involvement of the imine groups of the Schiff base in the complexation process. Furthermore, in order to broaden the applicability, the probe DPTZ-SB was applied in real water samples obtained from the local river, lake and tap water. Interestingly, a paper based fluorescent sensor was devised by embedding DPTZ-SB on the filter paper and was analyzed by a handheld UV lamp. Under UV light illumination, the paper-based sensor exhibited prominent fluorescence quenching in the presence of PA, which can be conveniently visualized. Moreover, the color-scanning application available in smart phones was coupled with the paper-based sensor to quantitate the scanometric assays. On a parallel note, DPTZ-SB showed excellent aggregation induced enhanced emission (AIEE) property. In fact, a 9.4-times enhancement in the photoluminescence (PL) intensity was noted for a 90:10 H2O:DMF of DPTZ-SB as compared to that in pure DMF. Therefore, the multifaceted applicability of the Schiff base has been explored, particularly in the fields of PA explosive detection device in real life samples and AIEE.

Coumarin-based two-photon AIE fluorophores: Photophysical properties and biological application

Based on the coumarin skeleton, we deliberately designed two groups of fluorophores, termed as Coum-R and Naph-Coum-R, using the diphenylamino group as the electron donor, which displayed long-wavelength emissions (red spectral region), large Stokes shift (up to 204 nm), superior AIE performance, and large two-photon absorbance cross-sections (as high as 365 GM). The electron-withdrawing substituents at the 3-position of these dyes could induce a significant red-shift in their emission spectra. Preliminary imaging experiments demonstrated the capability of these dyes as two-photon fluorophores for specifically staining lipid droplets in living cells.

Nonconjugated fluorescent polymer nanoparticles by self-assembly of PIMA-g-β-CD for live-cell long-term tracking

Fluorescent non-conjugated nanoparticles without any π-aromatic building blocks are of great interest in biological applications due to their low cytotoxicity and biocompatibility. Herein, the non-conjugated AIE-active polymer nanoparticles bearing β-cyclodextrin (β-CD-PNs) were obtained through self-assembly of amphiphilic poly(isobutylene-alt-maleic anhydride)-g-β-CD (PIMA-g-β-CD). Unexpectedly, β-CD-PNs without conventional AIE fluorophores showed strong fluorescence emission in the aggregated state, excellent photostability and water-solubility. More interestingly, β-CD-PNs showed excellent biocompatibility and low biotoxicity after being co-incubated with HeLa cells and passaged several times. As a result, the strong blue fluorescence signals could still be detected in HeLa cells after up to 15 generations of passages and showed complete cell morphology. Furthermore, β-CD-PNs could also be used in zebrafish for bioimaging. The results indicated that β-CD-PNs was a good choice as a tracer for long-term cell tracking and in vivo imaging agent. Our research provided an effective strategy for developing low-toxicity bioprobes based on β-CD.

Frontispiece: Supramolecular Assemblies with Aggregation‐Induced Emission Properties for Sensing and Detection

This article overviews the advanced structures and sensing properties of representative AIE-active supramolecular assemblies and illustrates the detection mechanism of the established sensing systems for monitoring particular analytes including metal ions, anions, organic pollutants, gases, biomolecules, and heparin drugs. The advantages, accessibility, and challenges of these systems based on commonly used AIE fluorophores are also discussed. For more information, see the Minireview by Y.-W. Yang et al. on page 22 ff.

A novel AIE fluorescent probe for β-galactosidase detection and imaging in living cells

An AIE fluorescent probe (TPh-PyBz-β-gal) was designed and synthesized for β-gal detection based on a novel AIE fluorophore and receptor unit D-galactose residue connected by glycosidic bond. The probe exhibited selective and sensitive turn-on fluorescent responses toward β-gal with detection limit reaching to 0.22 U/mL in aqueous environment. After studied from measured data, we proposed that a possible recognition mechanism probably resulted from the cleavage of glycosidic bond along with obviously increasing fluorescent signal at 606 nm. Meanwhile, TPh-PyBz-β-gal showed low cytotoxicity, and could be successfully used for β-gal imaging in cells.

Fluorescence imaging of surface-versatile latent fingerprints at the second and third level using double ESIPT-based AIE fluorophore

The nano-aggregates ofHPBIon both porous and non-porous surfaces provide fluorescent latent fingerprints with resolution up to the third level, which could be relocated on the tape.

Aggregation-induced emission fluorophores based on strong electron-acceptor 2,2'-(anthracene-9,10-diylidene) dimalononitrile for biological imaging in the NIR-II window.

In this communication, three novel donor-acceptor-donor type second near-infrared AIE fluorophores based on strong electron-acceptor 2,2'-(anthracene-9,10-diylidene) dimalononitrile have been successfully developed for bioimaging, in which they exhibit good photostability and can be used in mouse ear vessel imaging with high resolution (FWHM = 93.4 μm/SBR = 1.5) after capsuling in nanoparticles with good biocompatibility.

An organic microlaser based on an aggregation-induced emission fluorophore for tensile strain sensing

An organic microlaser based on a kind of innovative AIE fluorophore TPA-BDTO was fabricated by self-assembly method, and could be used for axial tensile strain sensing with high sensitivity and high resolution.

Conformational effect on fluorescence emission of tetraphenylethylene-based metallacycles

Herein, we designed and constructed two metallacycles, 1 and 2, to illustrate the conformational effect of isomeric AIE fluorophores on the platform of supramolecular coordination complexes (SCCs). Specifically, the dangling phenyl rings in TPE units of the metallacycle 1 align completely outside the main cyclic structure, while in the metallacycle 2, these phenyl rings align half inside and half outside. The experimental results showed that two metallacycles exhibited different behaviors in terms of AIE fluorescence and chemical sensing, which could be attributed to the subtle structural difference of the TPE units. This work represents the unification of topics such as self-assembly, AIE, and chemical sensing, and further promotes the understanding for the structure-property relationship of isomeric AIE fluorophores.

A three-photon probe for highly selective and sensitive detection of Ag+ bearing an AIE fluorophore

It is well known that the silver ions (Ag+) are important in the human body, however, novel probes were lacked with good water solubility, biocompatibility and deep penetration to detect Ag+ in the organism. In this work, we report two new three-photon absorption AIE luminogens (AIEgen), abbreviated as Tpy and Tpy-Hex, whereby Tpy-Hex could detect intracellular and environmental Ag+ quantitatively at a micromolar level. Tpy-Hex binding with Ag+ possesses enhanced three-photon absorption cross-section under1550 nm excitation (NIR II window), which is indeed beneficial for deep penetration in vitro and in vivo. The mechanism underlying the changes in three photon absorption spectra caused by bromohexyl chain substitution was further explored. The fluorescence bioimaging results reveal that the proposed probe Tpy-Hex could be ultra-sensitive for detection of Ag+ in HeLa cells and poisoned mice.

Thermally responsive AIE-active polyurethanes based on a tetraaniline derivative.

Polyurethanes with different soft–hard segment ratios were successfully synthesized, with an aggregation-induced-emission (AIE)-active tetraaniline derivative (NH2–B3–Ani4–NH2) as the hard segment. The resulting polyurethanes exhibited typical AIE features. The fluorescence intensities of polyurethane films changed with heat treatments. The fluorescence intensities of the polyurethane films decreased sharply after quenching treatment, yet their fluorescence intensities exceeded the original intensities of the films after thermal annealing at 80 °C for 24 h. Differential Scanning Calorimetry (DSC) results implied that the melting peaks in polyurethane films disappeared after quenching treatment, but the melting peaks appeared again after thermal annealing. These results proved that the arrangement of the structure had an important effect on the AIE properties of the polyurethane films. Meanwhile, the fluorescence intensities of these polyurethanes decreased with the increase of temperature, indicating that all three polyurethanes exhibited temperature-dependent fluorescent characteristics. Based on the above investigations, the AIE-active polyurethanes may provide a platform for the development of stimuli-responsive fluorescent materials.

A two-photon AIE fluorophore as a photosensitizer for highly efficient mitochondria-targeted photodynamic therapy

Nowadays, photodynamic therapy (PDT) has become an effective method for cancer therapy.

Optimising molecular rotors to AIE fluorophores for mitochondria uptake and retention.

Molecular rotors exhibit fluorescence enhancement in a confined environment and thus have been used extensively in biological imaging. However, many molecular rotors suffer from small Stokes shift and self-aggregation caused quenching. In this work, we have synthesised a series of red emissive molecular rotors based on cationic α-cyanostilbene. Profoundly enhanced aggregation-induced emission (AIE) properties and greatly widened Stokes shifts can be achieved by molecular engineering. With specificity to stain mitochondria, we demonstrate a simple approach to achieve cell uptake and retention upon tuning the pyridinium substituent of the dyes.