AIE-active Probe Research Articles

Development of an AIE-active fluorescent probe for the simultaneous detection of Al3+ and viscosity and imaging in Alzheimer’s disease model

Alzheimer’s disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer’s disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer’s disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence “turn on” modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

Synergistic integration of a rhodamine-labelled tripeptide into AIE-active fluorogenic probe: Enabling nanomolar detection of Al3+ ions through test strips, thin films, and Arduino-assisted optosensing platform

Peptide-fluorophore conjugates (PFCs) have been expeditiously utilized for metal ion recognition owing to their distinctive characteristics. Selective detection and quantification of aluminum is essential to minimize health and environmental risks. Herein, we report the synthesis and characterization of a new chemoprobe with aggregation-induced emission characteristics by chemically conjugating rhodamine-B fluorophore with a tripeptide. The probe revealed β-sheet secondary conformation in both solid and solution states, as confirmed by FT-IR, PXRD, and CD experiments. AIE characteristics of the probe in water-MeCN mixtures revealed the formation of spherically shaped nanoaggregates with an average size of 353 ± 7 nm, as confirmed by SEM, TEM, and DLS studies. The probe exhibited a large stokes shift (175 nm) and displayed selective colorimetric and fluorometric responses towards Al3+ ions with an extremely low detection limit (51 nm) and a fast response time (≤15 s). Comparative NMR studies confirmed the cleavage of spirolactam ring upon aluminum binding. The probe’s practicality was enhanced through integration into test strips and thin films, allowing solid-phase detection of Al3+ ions. Furthermore, an RGB-Arduino enabled optosensing device has been developed to enable instant quantifiable analysis of aluminum concentrations in real-time conditions.

Molecularly engineered high-performance AIE luminogen for NIR-III excitable deep-brain three-photon fluorescence imaging

Three-photon microscopy (3PM) utilizing near-infrared-III (NIR-III) excitation has emerged as an effective technology for deep-tissue bioimaging. Within this domain, organic small molecules with aggregation-induced emission (AIE) property prove to be promising candidates as high-quality 3PM imaging agents because of their exceptional optical properties and the general merit of biocompatibility that most organic small molecules possess. However, due to the bidirectional effects of the intrinsic structure distortion of AIE luminogens (AIEgens) on the three-photon absorption cross section (σ3) and fluorescence quantum yield (η), two crucial factors that determine 3PM performances, the development of high-powered AIE-active 3PM probes with robust ησ3 remains a formidable challenge. In this work, by synergistically integrating multiple beneficial principles into the molecule design, an innovative AIE-active 3PM probe with a symmetrical quadrupole D–A–D architecture, namely TIT, was successfully constructed. Owing to the harmonized planarity and distortion, as well as strong D–A interaction within TIT, the as-prepared TIT nanoparticles (NPs) exhibited boosted ησ3 under 1665 nm NIR-III excitation. This breakthrough enabled brain vascular imaging at a remarkable depth of 1895 μm after craniotomy, thus positioning TIT among the top three organic 3PM probes in terms of imaging depth. In addition, successful hemodynamic imaging at a depth of 1200 μm within the mouse brain post-craniotomy was also accomplished. These achievements establish TIT NPs as highly promising probes for in vivo deep-brain three-photon imaging.

Pyrene based AIE-active probe for selective detection of picric acid through the inner filter effect channel in aqueous medium

The development of pyrene derivatives possessing the AIE feature have emerged as an intriguing area of research with potential applications in several domains. In the present study, we designed and developed an AIE active pyrene derivative for picric acid sensing in an aqueous medium. The design based on a single step condensation reaction and the product has been meticulously characterized by using NMR and Mass spectrometric techniques. In comparison to pristine pyrene, the synthesized pyrene derivative has a lower bandgap energy as a result of the intramolecular charge transfer between pyrene and 4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile. The synthesized probe demonstrates a moderate level of fluorescence when dissolved in a solution, and it has exhibited a remarkable emission caused by aggregation at higher water percentages. The aggregates were meticulously characterized by DLS, SEM and TEM measurements. The spherically shaped aggregates have shown enhanced fluorescence quantum yield and lifetime, rendering them a more suitable option for sensor applications. The aggregates were effectively employed as a fluorescent probe for the detection of picric acid in an aqueous medium. The probe exhibited a notable level of selectivity and sensitivity towards picric acid, as evidenced by its low detection limit of 4.47 nM. Moreover, the quenching mechanism was ascribed to the inner filter effect, providing supporting evidence from both experimental and mathematical calculations. The findings indicate that the probe has potential as a feasible choice for a picric acid sensor.

Designing a multifunctional AIE active fluorescent Schiff base probe: Sensitive heavy metal ions recognition and water induced aggregation

A new multifunctional Schiff base probe AnQn containing dual fluorophore (anthracene-quinoline) has been synthesised via a facile one-pot reaction. This probe demonstrated the ability to selectively discriminate group IIIA metal...

Morphological adaptability through structural alterations in an AIE active novel chemosensor with Al(iii), Fe(iii), and gas phase/aqueous phase TNP recognition ability

In both solid and solution states, the detection of picric acid is achieved by using the AIE active probe H2L with different morphologies at different water percentages.

One-step synthesis of a dual-functional AIE-active probe for ClO- detection and photodynamic therapy.

An amphiphilic fluorescent probe (BHSMP) with aggregation-induced emission (AIE) features was synthesized via a one-step route. The probe showed high water dispersibility, low toxicity and the ability of selective and sensitive (limit of detection of 0.11 µM) detection of ClO- with fast-response (≤30 s) in aqueous solution and living organisms. Owing to the donor-acceptor (D-A) structure and existence of cationic groups, BHSMP could also generate reactive oxygen species under light-irradiation and potentially be utilized for photodynamic therapy. The strategy described in this work is of great significance for the design and synthesis of multifunctional AIE-active functional materials to facilitate their biomedical applications.

Naphthalimide-based AIE probe for direct and rapid detection of HSA in urine sample

Human serum albumin (HSA) is an important indicator for diagnose of renal injury. In this study, an AIE-active fluorescent probe (NI2) based on hindered amine modifying 1,8-naphthalimide molecule was designed for directly detecting HSA in urine samples without any pretreatment. NI2 exhibits red AIE fluorescence around 600 nm which is longer than previous reports based on 4-amino-1,8-naphthalimide derivatives contributed to its twisted intramolecular charge transfer (TICT) structure. An N-methyl pyridium cation group was introduced to interact with HSA for forming the aggregates with the “turn on” signal. Interestingly, the emission enhancement factor (I/I0) can increase obviously by addition of a mount of heparin. An optimized working medium with 5 μM heparin as additive was provided in which NI2 could detect HSA within a wide concentration range (0–10 μM) in the raw urine samples without any pretreatment. This protocol is rapidly (<60 s) and sensitively (LOD = 0.254 μM) that meets the requirement of liquid biopsy technology.

Synthesis of AIE-active glycopolymer probe via reversible deactivation radical polymerization for the fluorescent detection of boric acid in water

Excessive boric acid could cause severe damage to plants and humans. Hence, it is of great importance to detect its presence in water. However, traditional analytical methods often have to use either toxic reagents or expensive instruments, which urges the development of a facile detection strategy. Herein, we have designed a tetraphenylethylene-cored glucose-containing glycopolymer with an aggregation-induced emission effect to detect the concentration of boric acid in water efficiently. Copper-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) was utilized to polymerize glucose-containing monomer directly in N, N-dimethylbenzamide (DMF), yielding a star-shaped glycopolymer with a tetraphenylethylene core. This glycopolymer emitted fluorescence through B(OH)4− induced aggregation under alkaline conditions, which can serve as a sensitive fluorescence probe for detecting boric acid while being specific to the acid and not affected by other metal ions.

Bis-cyanostilbene based fluorescent materials: A rational design of AIE active probe for hypochlorite sensing

In the present investigation cyanostilbene based molecular probes, PCS and PCO, bearing N,N-dimethylthiocarbamate and N,N-dimethylcarbamoyal groups, respectively, have been synthesised. These probes exhibit AIEE activity in their aggregated state in the mixed solvent system of THF: H2O by way of turning on their emission, which has also been observed in powder, neat thin films and hybrid polymer films. While the probe PCO is silent to ClO−, PCS exhibits a significant response towards ClO− rationalised on the basis of HOCl specific oxidation of thiocarbamate, which is also extended to detect ClO− in water samples. Additionally, applicability of the test strips of PCS for rapid on-site detection of ClO− has been demonstrated. The experimental results are supplemented by the theoretical calculations wherever possible.

An AIE-active fluorescent probe with near-infrared (NIR) emission for selectively monitoring and bioimaging Cys in living cells

Cysteine (Cys), as a kind of essential bio-thiols, plays a pivotal role in modulating cell metabolism, maintaining intracellular redox balance and facilitating protein synthesis. In order to investigate its role in these physiological processes, fluorescent probe was selected as an important method for selectively detecting Cys. However, most of the probes possess ACQ effect, which limits their applications in the field of biosensing and bioimaging. Herein, an AIE-active fluorescent probe TCF-TPA was synthesized for specifically detecting Cys in HeLa cells. TCF-TPA, consisted of a tricyanofuran (TCF) fluorophore, was modified with an acrylate group for distinguish Cys from other bio-thiols, and the incorporation of electron-donating triphenylamine endowed the probe with AIE property and strong intramolecular charge transfer effect, thereby enabling the probe to have near-infrared (NIR) emission length (666 nm). Meanwhile, TCF-TPA possessed low detection limit for Cys (73.0 nM) and was successfully performed bioimaging of Cys in HeLa cells.

A pyrrole-tricyanofuran-based probe for the detection of bisulfite and viscosity in lysosomes of living cells and zebrafish

A novel AIE active bifunctional probe for detecting bisulfite (HSO3−) and viscosity synchronously was developed based on pyrrole-tricyanofuran skeleton. This probe exhibited aggregation-induced emission behavior in almost pure aqueous media, and responded to HSO3− with a “turn-off” signal and viscosity changes with a “turn-on” signal in semi-aqueous solutions, respectively. The response mechanism of the probe associated with HSO3−-involving CC breakage was demonstrated via ESI-MS, 1H NMR analysis, and density functional theory calculations. Furthermore, the probe has been applied to imaging endogenous HSO3− and viscosity changes in the lysosomes of C6 cells and zebrafish.

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.

Real-time tracking of endogenous CYP2J2 by red-emitting aggregation-induced emission probe with large Stokes shift

The abnormal expression of cytochrome P450 2J2 (CYP2J2) is closely related to the proliferation of human cancer cells. In this study, a red-emitting probe with an aggregation-induced emission (AIE) effect for the quantification of CYP2J2 was developed by modifying the typical AIE fluorescent group tetraphenylethylene (TPE) through two-step synthesis. Upon addition of CYP2J2, the probe underwent O-demethylation and spontaneously 1,6-elimination reactions of p-hydroxybenzyl that allowed it to alter its photophysical properties, thus realizing light-up detection of CYP2J2 with extremely large Stokes shift (236 nm), excellent sensitivity and selectivity, low detection limit (1.09 nM). Moreover, this new AIE-active probe with good biocompatibility was admirably employed to tracking endogenous CYP2J2 in living cells.

Interrogating the nature of aggregates formed in a model azine based ESIPT coupled AIE active probe: stark differences in photodynamics in the solid state and aggregates in water.

A novel Schiff base 4-bromo-2-((E)-((E)-(1-(naphthalen-2-yl)ethylidene)hydrazono)methyl)phenol (BNHMP) was synthesized and characterized by NMR, ESI-MS, FTIR and single crystal X-ray diffraction studies. In the solution phase, BNHMP shows prominent emission from the keto-form, a consequence of excited state intramolecular proton transfer (ESIPT). The quantum yield and excited state lifetime decrease in polar solvent THF compared to relatively non-polar solvent DCM. Interestingly, in aqueous solution (pH 7.0), the quantum yield along with the excited state lifetime undergoes tremendous increment. Dynamic light scattering experiments and FESEM reveal the formation of aggregates in water as reflected by the increased hydrodynamic radius of BNHMP in water. Hence, aqueous phase studies revealed BNHMP to be an AIE active probe. On the other hand, BNHMP shows huge emission intensity in the solid state. Interestingly, the emission decay behavior of BNHMP changes upon excitation, as BNHMP shows very broad absorption in the solid state. Upon excitation at 360 nm, a triexponential decay pattern is found, which changes to a biexponential one upon excitation at 450 nm. Meticulous analysis of the fluorescence lifetimes led to the assignment of J and H aggregates coexisting in the solid state with the former dominating the photodynamics. A judicious comparison of the lifetime behavior in the solid state to that in water leads to the conclusion that BNHMP undergoes AIE by the formation of J and H aggregates to an equal extent, a phenomenon starkly different from the solid-state scenario. The current results hold significance as this is among a few reports where such comprehensive spectrodynamic dissection has been performed for an ESIPT-AIE active Schiff base in solution as well as in the solid phase, thereby giving a holistic vision of the nature and fate of aggregation occurring in such azine based systems and subsequently advancing the understanding of such systems in terms of their photo behavior.

Long-term spatiotemporal and highly specific imaging of the plasma membrane of diverse plant cells using a near-infrared AIE probe.

Fluorescent probes are valuable tools to visualize plasma membranes intuitively and clearly and their related physiological processes in a spatiotemporal manner. However, most existing probes have only realized the specific staining of the plasma membranes of animal/human cells within a very short time period, while almost no fluorescent probes have been developed for the long-term imaging of the plasma membranes of plant cells. Herein, we designed an AIE-active probe with NIR emission to achieve four-dimensional spatiotemporal imaging of the plasma membranes of plant cells based on a collaboration approach involving multiple strategies, demonstrated long-term real-time monitoring of morphological changes of plasma membranes for the first time, and further proved its wide applicability to plant cells of different types and diverse plant species. In the design concept, three effective strategies including the similarity and intermiscibility principle, antipermeability strategy and strong electrostatic interactions were combined to allow the probe to specifically target and anchor the plasma membrane for an ultralong amount of time on the premise of guaranteeing its sufficiently high aqueous solubility. The designed APMem-1 can quickly penetrate cell walls to specifically stain the plasma membranes of all plant cells in a very short time with advanced features (ultrafast staining, wash-free, and desirable biocompatibility) and the probe shows excellent plasma membrane specificity without staining other areas of the cell in comparison to commercial FM dyes. The longest imaging time of APMem-1 can be up to 10 h with comparable performance in both imaging contrast and imaging integrity. The validation experiments on different types of plant cells and diverse plants convincingly proved the universality of APMem-1. The development of plasma membrane probes with four-dimensional spatial and ultralong-term imaging ability provides a valuable tool to monitor the dynamic processes of plasma membrane-related events in an intuitive and real-time manner.

A Highly Efficient Fluorescent Sensor Based on AIEgen for Detection of Nitrophenolic Explosives

The detection of nitrophenolic explosives is important in counterterrorism and environmental protection, but it is still a challenge to identify the nitroaromatic compounds among those with a similar structure. Herein, a simple tetraphenylethene (TPE) derivative with aggregation-induced emission (AIE) characteristics was synthesized and used as a fluorescent sensor for the detection of nitrophenolic explosives (2, 4, 6-trinitrophenol, TNP and 2, 4-dinitrophenol, DNP) in water solution and in a solid state with a high selectivity. Meanwhile, it was found that only hydroxyl containing nitrophenolic explosives caused obvious fluorescence quenching. The sensing mechanism was investigated by using fluorescence titration and 1H NMR spectra. This simple AIE-active probe can potentially be applied to the construction of portable detection devices for explosives.

A tetraphenylethene-based Schiff base AIEgen with a large Stokes shift as probe for highly sensitive and selective detection of aqueous Cu2+ ions and its application in cell imaging

In this work, an AIE-active tetraphenylethene-based Schiff base fluorescent probe 3 with a large Stokes shift (247 nm) was designed and synthesized. It was found that the aggregated probe 3 exhibited very high selectivity and anti-interference ability for Cu2+ in PBS buffer (70% fw) through a fluorescence “turn–off” strategy. Job’s plot and NMR analysis indicated the two phenolic hydroxyl groups of the benzene ring and the N atom (-CH=N-) on probe 3 interacted with Cu2+ ions in a 1:1 stoichiometric ratio. A comprehensive analysis of the Stern–Volmer and binding constant indicated a rather strong interaction between probe 3 and Cu2+ ions. Probe 3 illustrated excellent sensitivity toward Cu2+ under ppb level (4.5 nM) and achieved more than 95% recovery in river, lake and tap water toward estimation of Cu2+ ions in the analytical applications. Moreover, probe 3 was able to realize bioimaging of HepG2 cells and be quenched by intracellular Cu2+ ions, making it promising as a sensitive Cu2+ sensor for organisms.

A lipid droplet-targeted multifunctional AIE-active fluorescent probe for hydrogen peroxide detection and imaging-guided photodynamic therapy

Recent developments of activatable photosensitizers (aPSs) invigorate photodynamic therapy by enhancing sensitivity towards cancer cells and avoiding constant phototoxicity. However, the diversity of activatable photosensitizers needs to be developed urgently. Hydrogen peroxide (H2O2), as a typical biomarker which overexpressed in tumor tissue, is an ideal promoter for selectively activating photosensitizers to restore their photosensitivity. Herein, we construct a new H2O2-activated photosensitizer DPP-BPYS based on diketoprrrolopyrrole (DPP), which can rapidly and specifically respond to H2O2 both in vitro and in vivo, and exhibit “turn-on” near-infrared fluorescence emission. The activated DPP-BPYS performs typical aggregation-induced emission (AIE) characteristics, a large Stokes shift (180 nm), strong fluorescence quantum yield and high singlet oxygen (1O2) generating capacity. More importantly, activated DPP-BPYS can target lipid droplets (LDs) in tumor cells to form aggregates, and effectively generate reactive oxygen species under white light irradiation to induce apoptosis of tumor cells. Consequently, this research provides a unique molecular tool for H2O2-activated photodynamic anticancer therapy.

Rational construction of an AIE-active fluorescent probe bearing three reaction sites for individual and continuous detection of H2S and HClO with single-wavelength excitation

Endogenous H2S and HClO play vital roles in regulating the redox status in vivo, and are involved in many pathophysiological events. Accordingly, accurate sensing and imaging of intracellular H2S and HClO have become greatly in demand. However, conventional double-response fluorescent probes for these two substances suffered from the notorious aggregation-caused quenching effect and required multiple excitations to achieve discrimination determination. In this study, we firstly constructed an AIE-active fluorescent probe with three potential reaction sites for individual and continuous detection of H2S and HClO using a single excitation wavelength. The multiple-site probe exhibited distinctive fluorescence behaviors to H2S and HClO with fast response (H2S: 12 min; HClO: 1.8 min), well-separated emission peaks (88 nm), high sensitivity and good selectivity due to H2S-induced thiolysis of 2,4-dinitrophenyl ether assisted by an adjacent aldehyde and HClO-triggered sulfur oxidation. The corresponding recognition mechanisms were fully confirmed by HRMS, 1H NMR and control experiments. Moreover, the probe was successfully utilized for separate and continuous imaging of intracellular H2S and HClO in different fluorescent channels, indicating its potential for further study the biological functions of H2S and HClO in living systems.