Aggregation-induced Emission Research Articles

Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy.

Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial mitochondria-derived vacuolation, accompanied by reactive oxygen species generation, decreased mitochondrial membrane potential, and intracellular Ca2+ overload, thereby disrupting metabolisms and inducing nonapoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 and TriPEX-PF6 successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy postintravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to Temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.

Application of Aggregation-Induced Emission (AIE) Technology in Monitoring of the Preparation of Spinning Solution for Electrospinning

Application of Aggregation-Induced Emission (AIE) Technology in Monitoring of the Preparation of Spinning Solution for Electrospinning

Supradecoration induced novel Properties: A comparative study of Ferrocene and Ferrocenyl α-aminophosphonate

Decorating chemical motifs with appropriate functional groups capable of supramolecular interactions hold key in modulating these novel systems for targeted applications. This work by means of a comparative study of Ferrocene and Ferrocenyl α- aminophosphonate highlight supradecoration induced multi paradigm properties across materials to medicine. The observed results indicate an increase in crystal framework energy with induction of mechanochromism and aggregation-induced emission in case of Ferrocenyl-α-amino phosphonate as novel supra decorated Ferrocene motif. Comparative BSA and BLC studies indicated improved biocompatibility with enhancement of catalase enzyme activity in case of Ferrocenyl-α- aminophosphonate compared to pristine Ferrocene. The relative quantification of intermolecular non covalent interactions of Ferrocene and Ferrocenyl-α- aminophosphonate evaluated using Quantum crystallographic methods and non-covalent interaction analysis were used to corroborate the supramodulation effects. The observed influence of Ferrocenyl α-aminophosphonate on the enzymatic activity of catalase was also examined using a comparative molecular docking analysis. The docking results corroborated influence of supradecoration on binding affinity and binding site, which are vital for designing ligands of enhanced catalase activity and also helpful in prediction of newer regulatory sites on enzyme. Taken together this work signifies how supra decoration of Ferrocene motif with functionalities capable of diverse intermolecular non-covalent interactions modulate molecular properties for newer applications.

Twisted Structure Induced Solid-State Fluorescence and Room-Temperature Phosphorescence from Furan-Based Carbon Dots.

Boron doping can effectively induce solid-state fluorescence (SSF) in carbon dots (CDs); however, research on the intrinsic mechanism underlying this phenomenon is lacking. Herein, a design strategy for boron-doped furan-based CDs is proposed, CDs with aggregation-induced emission (AIE) properties are synthesized, and the mechanism by which boron atom dopants induces SSF and room-temperature phosphorescence (RTP) is elucidated. The morphology and structural characterization of the CDs indicate that boron doping leads to structural twisting of the CDs. The AIE phenomenon of CDs arises from the inhibition of the twisted structure motions and a reduction in the nonradiative relaxation rate during the aggregation process. In addition, CDs with twisted structures exhibit a smaller overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), effectively reducing the singlet-triplet splitting energy (ΔEST). CDs embedded in microcrystalline cellulose (MCC) exhibit green RTP because the nonradiative transitions are suppressed, and the excited triplet species remain stable. For the first time, this study reveals the structure-activity relationship between the twisted structure and optical properties of CDs, providing a new approach for the preparation of solid-state light-emitting CDs.

Natural AIEgens as Ultraviolet Sunscreens and Photosynergists for Solar Fuel Production.

Bio-nano hybrids (BNH), combining semiconductors and microorganisms, have shown great promise for effective solar-to-fuel energy conversion. However, the high-energy ultraviolet (UV) photons in the solar spectrum can cause severe photocorrosion of semiconductors and irreversible photodamage to microorganisms within BNH. Here, we developed an encapsulation strategy using natural luminogens with aggregation-induced emission characteristics (AIEgens) to construct a protective layer for BNH, effectively shielding them against high-energy UV photons. We incorporated natural berberine (BBR) into the BNH composed of Methanosarcina barkeri and polymeric carbon nitrides (CNx). The self-assembled BNH-BBR system displayed a 2.75-fold higher CH4 yield than BNH under simulated solar irradiation. Mechanism analysis revealed that BBR acted as a UV sunscreen for BNH by converting high-energy short wavelengths into low-energy long wavelengths, thereby reducing the accumulation of reactive oxygen species and alleviating the photocorrosion of CNx. Furthermore, BBR functioned as a photosynergist for BNH by regulating photoelectron production and utilization, enhancing the intracellular energy formation in M. barkeri for growth and metabolism. This work provides important insights into the effective and scalable conversion of CO2 into valuable biofuels with BNH under light illumination containing high-energy photons.

Tetraphenylethene-Based Ni8-Pyrazolate Metal-Organic Framework for Photoredox/Nickel Dual Catalysis of C-S Cross-Coupling.

As a prototypical aggregation-induced emission luminogen (AIEgen), the tetraphenylethene (TPE) moiety has been judiciously modified as organic linkers for constructing various functional metal-organic frameworks (MOFs). However, these AIEgen-based MOFs have rarely received research attention in photocatalytic applications due to their limited stability in harsh reaction conditions. In this work, we report a robust Ni8-pyrazolate-based MOF (denoted as TPE4Pz-Ni) under the guidance of reticular chemistry, which is assembled by an AIE-active tetratopic linker of 1,1,2,2-tetrakis(4-(1H-pyrazol-4-yl)phenyl)ethane (H4-TPE4Pz) with a 12-connected Ni8-cluster of [Ni8(OH)4(H2O)2Pz12] (Pz = pyrazolate) in a (4,12)-connected ftw-a topological network. Notably, MOF TPE4Pz-Ni exhibits excellent stability in a wide range of solvents and even in a saturated NaOH solution. Moreover, its luminescent emission is effectively quenched via a ligand-to-metal charge transfer (LMCT) process originating from the TPE-cored linker to the Ni8 cluster, which enables TPE4Pz-Ni to act as an efficient photoredox/nickel dual catalyst for light-mediated C-S cross-coupling reactions between various aryl iodides and thiols.

Decarboxylative Aminomethylation of Indole-3-carboxylic Acids via Strain Release-Driven Ring Opening of 1,2-Oxazetidines.

A copper-catalyzed decarboxylative aminomethylation of indole-3-carboxylic acids with 1,2-oxazetidines has been developed, enabling the rapid synthesis of structurally diverse 3-aminomethylindoles in good to excellent yields. Remarkably, an unprecedented decarboxylative aminomethylation/cyclization cascade was further achieved by a combination of copper and iron salts to construct complex γ-carbolines with high efficiency. It is worth noting that one of the obtained products proved to be a good dual-emissive luminogen, exhibiting both aggregation-caused quenching and aggregation-induced emission.

AIE pyrene-based luminescent zinc MOF for selective and sensitive ATP and ADP sensing in water by analyte-induced structure decomposition

Adenosine triphosphate (ATP) is a natural and universal energy carrier that produces adenosine diphosphate (ADP) by releasing chemical energy through hydrolysis, which plays a key role in various biological processes. Hence, the design of probes for the selective ATP and ADP sensing among various nucleosides is significant. In this work, 4,4′-(pyrene-1,6-diyl)dibenzoic acid (H2PDBA) has been synthesized and shows an aggregation-induced emission (AIE) effect in a THF-H2O mixture at 10 % water fraction. Based on H2PDBA, a new zinc metal–organic framework (MOF), namely {[Zn(PDBA)]·2(CH3)2NH}n (Zn-MOF, PDBA = deprotonation of H2PDBA), has been constructed under hydrothermal conditions with a coordination-induced emission (CIE) effect. Significantly, Zn-MOF has been utilized to detect ATP and ADP in water with high selectivity and quick response time (within 1 min) by fluorescence quenching. The Ksv values and detection limits have been measured to be 7.83/8.78 × 103 M−1 and 0.82/1.71 μM for ATP and ADP, respectively. The sensing mechanism investigation indicates that the interactions between the ATP or ADP and Zn2+ nodes of the framework lead to the partial collapse of the framework, followed by the release of the ligand H2PDBA with weak luminescence in pure water. Moreover, Zn-MOF has successfully been applied for the determination of ATP and ADP with the recovery method by using fetal bovine serum samples.

Advanced AIE Materials for Environmental Monitoring: Selective Sensing of Thorium(IV) in Aquatic Systems.

Thorium (Th) is commonly used in various applications, but its long-term exposure poses health risks, necessitating its detection in aqueous environments. Traditional methods such as inductively coupled plasma mass spectrometry are sensitive but require complex instrumentation. Optical sensors, particularly fluorometry-based methods, are simpler, cost-effective, and selective. However, developing effective aggregation-induced emission (AIE) turn-on sensors for Th(IV) requires water-soluble fluorophores with a low background fluorescence. In the present work, we report a turn-on detection method for Th(IV) based on the AIE of the fluorophore tetra(4-sulfophenyl) ethylene (SuTPE). Th(IV)-induced aggregation of SuTPE and the simultaneous drastic enhancement of the emission property of SuTPE have been utilized for the selective sensing of Th(IV) in 100% aqueous media. The sensing mechanism was explored using ground-state absorption, steady-state and time-resolved emission, FTIR, DLS, SEM, AFM and quantum chemical studies of the SuTPE-Th(IV) complex. The selectivity of the present probe toward Th(IV) ions has been established by studying the interference of several metal ions, including lanthanides and uranyl ions. The LOD for Th(IV) was estimated to be 240 nM (56 ppb). The performance of the probe was demonstrated in tap water and diluted seawater matrixes. This work provides a significant advance for Th(IV) detection in aqueous environments, with implications for environmental monitoring and health safety.

Helical Star-Shaped Bottlebrush Polymers: From Controlled Synthesis to Tunable Photoluminescence and Circularly Polarized Luminescence.

The controlled synthesis of star-shaped bottlebrush polymers with tunable topologies is a challenge. However, such materials may exhibit distinct photoluminescence properties. Bottlebrush polymers have polymerization-induced emission (PIE) properties due to their aggregated side chains, and aggregation-induced emission (AIE) is also a unique luminescent property. In this work, we prepared a variety of highly active alkyne Pd catalysts and polymerized poly(L/D-lactic acid) macromonomers containing polymerizable phenylisocyanide groups as end groups to obtain a variety of topologically structured bottlebrush polymers with controllable molecular weights and narrow molecular weight distributions. Bottlebrush polymers with tetraphenyl ethylene (TPE) units as the core exhibit tunable photoluminescence and circularly polarized luminescence properties. We propose that such properties are due to the unique AIE characteristics of the TPE unit combined with the PIE characteristics of the bottlebrush polymer.

Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine.

Biopsy, including tissue and liquid biopsy, offers comprehensive and real-time physiological and pathological information for disease detection, diagnosis, and monitoring. Fluorescent probes are frequently selected to obtain adequate information on pathological processes in a rapid and minimally invasive manner based on their advantages for biopsy. However, conventional fluorescent probes have been found to show aggregation-caused quenching (ACQ) properties, impeding greater progresses in this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) have promoted rapid advancements in molecular bionanomaterials owing to their unique properties, including high quantum yield (QY) and signal-to-noise ratio (SNR), etc. This review seeks to present the latest advances in AIEgen-based biofluorescent probes for biopsy in real or artificial samples, and also the key properties of these AIE probes. This review is divided into: (i) tissue biopsy based on smart AIEgens, (ii) blood sample biopsy based on smart AIEgens, (iii) urine sample biopsy based on smart AIEgens, (iv) saliva sample biopsy based on smart AIEgens, (v) biopsy of other liquid samples based on smart AIEgens, and (vi) perspectives and conclusion. This review could provide additional guidance to motivate interest and bolster more innovative ideas for further exploring the applications of various smart AIEgens in precision medicine.

Three‐Component Synthesis of Fluorescent 1,4‐Benzothiazin‐2‐ones Through Thiol‐Free Iodine‐Catalyzed Cyclization

AbstractA convergent synthesis of 2H‐benzo[b][1,4]thiazin‐2‐one was achieved via iodine‐catalyzed three‐component reaction. This strategy involves the formation of two new C−S bonds and a C−N bond from the readily available precursors ‐ aryl methyl ketones, p‐anisidine, and elemental sulfur to generate the desired heterocycle in moderate to good yields. As the synthesized benzothiazine‐2‐ones are fluorescent under UV light, photophysical properties like solid‐state emission, solvatochromism, Aggregation Induced Emission (AIE), and the relative quantum yields of the compounds were measured which proves them to be a potential candidate for the development of optoelectronic devices.

Enhancement of Growth and Lipid Production in Microalgae Using Aggregation-Induced Emission Based Luminescent Material for Sustainable Food and Fuel.

AIEbased nanomaterials are progressively gaining momentum owing to their evolvement into an interdisciplinary field ranging from biomass and biomolecule yield to image-guided photodynamic therapy. This study focuses on a novel strategy to enhance growth, lipid accumulation, and in vivo fluorescence visualisation in green microalgae Chlamydomonas reinhardtii using AIE nanoparticles to quantify radical changes. The absorption of AIE photosensitiser, TTMN was recorded from 420 to 570 nm with a peak at 500 nm, and the emission ranged from 550 to 800 nm with a peak at 650 nm. As a ROSmolecule, H2O2 generation of TTMN in C. reinhardtii cells was detected with AIE nanoprobes TPE-BO. H2O2 accumulation increased with the increase of TTMN concentrations. The maximum growth was observed at 10 µM TTMN-exposed C. reinhardtii cells. Significant lipid accumulation was found in both 10 and 15 µM TTMN-treated cells. For lipid visualisation, an AIE nanoprobe, 2-DPAN was used, and superior fluorescence was determined and compared with the traditional BODIPY dye. Cytotoxicity analysis of 10 µM TTMN on the HaCat cell line with 86.2% cell viability revealed its high biocompatibility on living cells. This AIE-based nanotechnology provides a novel approach for microalgae-derived sustainable biomass and eco-friendly biofuel production.

An Aggregation-Induced Emissive Platinum(II) Metallacycle as the Energy Donor of Rhodols for Ratiometric Detection of Hydrazine.

Industry-produced hydrazine (N2H4) is released into the environment, posing a major risk to human health and the ecosystem. Therefore, it is imperative to develop an effective and convenient method for the detection of N2H4. Herein, artificial light-harvesting systems (ALHSs) for N2H4 detection were constructed by applying an aggregation-induced emission-active platinum(II) metallacycle (TPEMc) as the energy donor and rhodols (P1, P2, and P3) as the energy acceptors. The ratiometric fluorescence probes based on ALHSs for N2H4 showed obvious signal amplification and lower limits of detection compared to those of rhodols (P1, P2, P3) alone. The TPEMc-rhodols systems clearly demonstrated a noticeable increase in fluorescence intensity at 550 nm and an obvious fluorescent color shift from cyan to yellow in the presence of N2H4. Fascinatingly, N2H4 could be visually and quantitatively detected in water by the TPEMc-rhodol systems paired with smartphone RGB analysis. Therefore, the combination of platinum(II) metallacycle with rhodols is a promising strategy for simple, sensitive, and visual detection of N2H4.

AIE-based ruthenium complexes as photosensitizers for specifically photo-inactivate gram-positive bacteria

The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.

Organophosphorus Hydrolase-like Nanozyme with an Activity-Quenched Aggregation-Induced Emission Effect: A Self-Reporting and Specific Assay of Nerve Agents.

Given the promising prospect of aggregation-induced emission luminogens (AIEgens) in fluorescence assays, it is interesting and significant to endow AIEgens with molecular recognition capability (such as enzyme-like activity). Here, an AIE nanomaterial with intrinsic enzyme-like activity (named as "AIEzyme") is designed and synthesized via a facile coordination polymerization of Zr4+ and AIE ligands. AIEzyme possesses enhanced and stable fluorescence in different solvents because of the AIE effect of ligands in the rigid structure of a coordination polymer. On the other hand, the organophosphorus hydrolase (OPH)-mimicking activity of AIEzyme exhibits excellent affinity and specific activity. Interestingly, the OPH-like activity can quench the inherent fluorescence of AIEzyme by the hydrolysate of a typical organophosphorus nerve agent (OPNA), diethyl-4-nitrophenylphosphate. Due to the sensitive activity-induced quenching effect for AIE, the self-reporting fluorescence assay method based on AIEzyme was established, which shows ultrahigh sensitivity, high selectivity, good storage stability, and acceptable reliability for a real sample assay. Moreover, the simultaneous colorimetric method broadens the detection range and the application scenarios. The proposed assay method avoided the interference of O2 during detection because the OPH-like activity does not derive from the generation of ROS. As a bonus, AIEzyme can also be used for the degradation of OPNAs by OPH-like activity, and the process can be self-monitored by AIE quenching. This work would provide a new opportunity for expanding the application of AIEgens and artificial enzymes by endowing AIEgens with enzyme-like activity.

Microenvironment-Activatable Probe for Precise NIR-II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) represents an insidious autoimmune inflammatory disorder that severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, posing a serious public health problem. Here, an advanced theranostic probe is introduced that integrates activatable second near-infrared (NIR-II) fluorescence imaging for precise RA diagnosis with multi-pronged RA treatments. A novel molecular probe comprising a long-wavelength aggregation-induced emission unit and a manganese carbonyl cage motif is synthesized, which enables NIR-II fluorescence activation and concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed joint microenvironment. This molecular probe self-assembles into a biocompatible nanoprobe, which is subsequently conjugated with anti-IL-6R antibody to afford active-targeting ability of RA. The nanoprobe exhibits significant turn-on NIR-II fluorescence signal at the RA lesion, enabling highly sensitive RA diagnosis and real-time therapeutic monitoring. The combination of ROS scavenging, on-demand CO gas release, and IL-6 signaling blockade results in potent therapeutic effect and synergistic immunomodulation impact, significantly alleviating the RA symptoms and preventing joint destruction. This research introduces a novel paradigm for the development of high-performance, activatable theranostic strategies to facilitate precise detection and enhanced treatment of RA-related diseases.

Fluorescent Ionic Liquid Aggregates: A Self-Assembled Approach for Pesticide Detection and Catalysis.

The unregulated use of pesticides, industrial discharge of heavy metals, waste, and agricultural runoff may contaminate surface water and groundwater, consequently threatening ecosystems and human health. Thus, the sensitive detection and degradation of pesticides are essential for safety. In this context, herein, we have developed benzimidazolium-based fluorescent surfactant assemblies TA-1/SDS and TA-2/SDBS, which exhibit aggregation-induced emission enhancement in an aqueous medium. The aggregates (TA-1/SDS and TA-2/SDBS) displayed a turn-on emission response upon interaction with carbendazim and azamethiphos with limits of detection 7.5 and 7.8 nM, respectively. The FE-SEM and AFM studies revealed that TA-1/SDS and TA-2/SDBS undergo self-assembly with the addition of AZA and CBZ, resulting in the formation of dendritic structures. In addition to the quantification of AZA and CBZ, TA-1/SDS and TA-2/SDBS have also been evaluated to degrade both pesticides and validated using 31P NMR spectroscopy and LC-MS spectrometry.

New AIEgens based on thieno[2,3-d]pyrimidine derivatives: Synthesis, DFT calculations, and molecular docking

In this paper, new thieno[2,3-d]pyrimidine analogs have been synthesized and characterized through different spectroscopic techniques. The photophysical properties of the molecules (7b-7f) and the quantum chemical calculations have been investigated. These molecules exhibited aggregation-induced emission behavior and showed efficient emission in both solid and solution states. A shift toward shorter wavelengths (hypsochromic shift) was observed when transitioning from the solution to the solid state, which could be explained by photoinduced intramolecular charge transfer (ICT) processes. DFT calculations confirmed that the diverse behavior of the thieno[2,3-d]pyrimidine analogs could be attributed to variations in molecular packing and rigidity. This study illustrates how luminophores aggregation can occur without significantly impacting the excited state, emphasizing the unconventional behavior resulting from minor alterations in terminal substituents. These findings hold implications for the advancement of luminescent materials. Additionally, theoretical calculations were conducted to compare the excitations and emissions of the new AIEgens with practical observations. Furthermore, a molecular docking study of the five AIEgens suggested their potential utility as anticancer drugs. Compound 7c exhibited a high affinity for human cyclin-dependent kinase 2 (CDK-2) protein, with a binding energy of 9.6 kcal/mol, indicating its potential as an inhibitor for this specific protein.

Novel Chiral Self-Assembled Nano-Fluorescence Materials with AIE Characteristics for Specific Enantioselective Recognition of L-Lysine.

In this paper, two aggregation-induced emission (AIE) chiral fluorescent materials, S-1 and S-2, were synthesized. The two materials are based on BINOL and H8-BINOL backbones, respectively, and large electron-absorbing groups are attached to the chiral backbones through the Knoevenagel reaction. At the same time, the CD signals of these two chiral fluorescent materials are gradually weakened (fw gradually increases) as they continue to aggregate. However, S-2 underwent a flip-flop from a negative to positive chiral CD signal at fw ≥ 90. And both materials also showed significant enantioselective recognition of lysine, demonstrating their potential as novel chiral fluorescent probes. Among them, the enantioselective fluorescence enhancement ratios (ef) of S-1 and S-2 for lysine were 10.0 and 10.3, respectively, while different degrees of blue shifts were produced by the ICT mechanism during the recognition process. In addition, the self-assembled morphology of the two nanomaterials is different; S-1 comprises hollow-core vesicles that are more likely to aggregate to form larger self-assembled vesicles, whereas S-2 is a solid block structure. When L/D-lysine was added alone, the morphology of S-1 was more distinctly different compared to S-2. With the addition of L-lysine, S-1 was dispersed and regularly spherical, whereas with the addition of D-lysine, S-1 itself remained in the form of aggregated large vesicles. This suggests that both S-1 and S-2 are important in the fields of chiral optics, chiral recognition, and nanoscale self-assembly.