Planar AIEgens with Enhanced Solid‐State Luminescence and ROS Generation for Multidrug‐Resistant Bacteria Treatment

Planar luminogens have encountered difficulties in overcoming intrinsic aggregation‐caused emission quenching by intermolecular π‐π stacking interactions. Although excited‐state double‐bond reorganization (ESDBR) can guide us on designing planar aggregation‐induced emission (AIE) luminogens (AIEgens), its mechanism has yet been elucidated. Major challenges in the field include methods to efficiently restrict ESDBR and enhance AIE performance without using bulky substituents (e.g., tetraphenylethylene and triphenylamine). In this study, we rationally developed fluoro‐substituent AIEgens with stronger intermolecular H‐bonding interaction for restricted molecular motions and increased crystal density, leading to decreased nonradiative decay rate by one order of magnitude. The adjusted ESDBR properties also show a corresponding response to variation in viscosity. Furthermore, their aggregation‐induced reactive oxygen species (ROS) generations have been discovered. The application of such planar AIEgen in treating multidrug‐resistant bacteria has been demonstrated in a mouse model. The relationship between ROS generation and distinct E/Z‐configurational stacking behaviors have been further understood, providing a design principle for synthesizing planar AIEgen‐based photosensitizers.     

Tetraphenylpyrazine-based AIEgens: facile preparation and tunable light emission

Research on aggregation-induced emission (AIE) has been a hot topic. Due to enthusiastic efforts by many researchers, hundreds of AIE luminogens (AIEgens) have been generated which were mainly based on archetypal silole, tetraphenylethene, distyrylanthracene, triphenylethene, and tetraphenyl-1,4-butadiene, etc. To enlarge the family of AIEgens and to enrich their functions, new AIEgens are in high demand. In this work, we report a new kind of AIEgen based on tetraphenylpyrazine (TPP), which could be readily prepared under mild reaction conditions. Furthermore, we show that the TPP derivatives possess a good thermal stability and their emission could be fine-tuned by varying the substituents on their phenyl rings. It is anticipated that TPP derivatives could serve as a new type of widely utilized AIEgen, based on their facile preparation, good thermo-, photo- and chemostabilities, and efficient emission.     

Sub-10 nm Aggregation-Induced Emission Quantum Dots Assembled by Microfluidics for Enhanced Tumor Targeting and Reduced Retention in the Liver

A robust platform is developed to assemble sub-10 nm organic aggregation-induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near-infrared window (NIR-II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm³ and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off-targeting to the liver than AIE dots.     

Lighting up rotaxanes with AIEgens

Aiming at the construction of novel rotaxanes with desired luminescent properties for practical applications, recently the rapid development of rotaxanes decorated with aggregation-induced emission(AIE) luminogens(i.e., AIEgens) has been witnessed. The combination of AIEgens and rotaxanes leads to the successful construction of a novel type of luminescent rotaxanes with many attractive features. In particular, the unique controllable dynamic feature of rotaxanes endows the resultant AIEgen-based...     

Bridged Stilbenes: AIEgens Designed via a Simple Strategy to Control the Non-radiative Decay Pathway

To broaden the application of aggregation-induced emission (AIE) luminogens (AIEgens), the design of novel small-molecular dyes that exhibit high fluorescence quantum yield (Φ_fl) in the solid state is required. Considering that the mechanism of AIE can be rationalized based on steric avoidance of non-radiative decay pathways, a series of bridged stilbenes was designed, and their non-radiative decay pathways were investigated theoretically. Bridged stilbenes with short alkyl chains exhibited a strong fluorescence emission in solution and in the solid state, while bridged stilbenes with long alkyl chains exhibited AIE. Based on this theoretical prediction, we developed the bridged stilbenes BPST[7] and DPB[7], which demonstrate excellent AIE behavior.     

Enantioselective recognition based on aggregation-induced emission

Chirality is one of the most important features of the nature. The recognition of enantiomers plays significant roles in the field of life science, pharmaceutical analysis and food chemistry. Among various recognition methods, fluorescence spectrometry has attracted much attention of researchers thanks to its high sensitivity and easy operation. Compared with traditional fluorescent probes, chiral molecules with aggregation-induced emission (AIE) have drawn increasing interests due to their huge potential in high-efficiency chemo/biosensors and solid emitters. Chiral AIE luminogens (AIEgens) can not only discriminate two enantiomers with excellent enantioselectivity, but also show general applicability for many chiral analytes, such as chiral acids, amino acids, amines, alcohols. In this review, we mainly summarized the recent development of chiral probes with AIE properties, including chiral tetraphenylethylene (TPE) derivatives, α-cyanostilbene derivatives, Schiff base derivatives and other AIEgens. Their synthetic routes, recognition capabilities and possible working mechanisms were well discussed. It is envisioned that the present review can give some significant guidance for design and synthesis of chiral AIEgens with good enantioselectivity and inspire more readers to join the research of chiral AIE.     

Recent Advances of AIEgens for Targeted Imaging of Subcellular Organelles

Fluorescence imaging based on luminogens with aggregation-induced emission(AIE)effect has drawn great attention in recent two decades,due to their superior advantages to overcome the technical difficulties.Thus,the AIE-active bioprobes with targeted ability at the subcellular level have been widely investigated to visualize the subcellular structures and monitor the biological processes.Considering the very rapid developments and the significance of selective imaging of subcellular structures,we summarize the recent two-year achievements about the AIEgens for targeted imaging of subcellular organelles including nuclei,membranes,lipid droplets(LDs),endoplasmic reticulum(ER),lysosomes,mitochondria and cytoplasm.The designed protocols and advantages of AIEgens,their mechanisms for targeted staining at organelles and the imaging performance are discussed.These AIE bioprobes exhibit great potentials for early diagnosis and therapeutics of diseases that related to subcellular organelles.Finally,the perspectives about AIEgens for these applications are also discussed.     

Construction and regulation of imidazo[1,5-a]pyridines with AIE characteristics via iodine mediated Csp2−H or Csp−H amination

The widespread applications of aggregation-induced emission luminogens (AIEgens) inspire the creation of AIEgens with novel structures and functionalities. In this work, we focused on the direct and efficient synthesis of a new type of AIEgens, imidazo[1,5-a]pyridicne derivatives, via iodine mediated cascade oxidative Csp²–H or Csp–H amination route from phenylacetylene or styrenes under mild conditions. The resulted compounds showed excellent AIE characteristics with tunable maximum emissions, attractive bioimaging performance, and potential anti-inflammatory activity, which exert broad application prospects in material, biology, medicine, and other relevant areas.     

1+1>2: Fiber Synergy in Aggregation-Induced Emission

Mesoscopic aggregate is important to transfer or even amplify the molecular information in macroscopic materials. As an important branch of aggregate science, aggregation-induced emissive luminogens (AIEgens) often show slight or even no emission in solutions but exhibit bright emission when they aggregate, which open a new avenue for the practical applications. Due to the flexible and rotor structure of AIEgens, the aggregate structure of AIEgens is highly sensitive to the surrounding microenvironment, resulting in adjustable optical properties. Fibers integrated of a multiplicity of functional components are ideal carriers to control the aggregation processes, further assembly of fibers produces large-scale fabrics with amplified functions and practical values. In this Concept article, we focus on the latest advances on the synergy between “AIE+Fiber” for the boosted performance that beyond AIE, and their applications are presented and abstracted out to stimulate new ideas for developing “AIE+Fiber” systems.     

Design and Development of Axially Chiral Bis(naphthofuran) Luminogens as Fluorescent Probes for Cell Imaging

Designing chiral AIEgens without aggregation-induced emission (AIE)-active molecules externally tagged to the chiral scaffold remains a long-standing challenge for the scientific community. The inherent aggregation-caused quenching phenomenon associated with the axially chiral (R)-[1,1′-binaphthalene]-2,2′-diol ((R)-BINOL) scaffold, together with its marginal Stokes shift, limits its application as a chiral AIE-active material. Here, in our effort to design chiral luminogens, we have developed a design strategy in which 2-substituted furans, when appropriately fused with the BINOL scaffold, will generate solid-state emissive materials with high thermal and photostability as well as colour-tunable properties. The excellent biocompatibility, together with the high fluorescence quantum yield and large Stokes shift, of one of the luminogens stimulated us to investigate its cell-imaging potential. The luminogen was observed to be well internalised and uniformly dispersed within the cytoplasm of MDA-MB-231 cancer cells, showing high fluorescence intensity.     

Biocompatible and noncytotoxic nucleoside-based AIEgens sensor for lighting-up nucleic acids

Aggregation-induced emission luminogens (AIEgens) have been used in biomacromolecules detection. Herein, TPE-dC and TPE-dU acted as the nucleoside-based AIEgens sensors in the first case, which can be used to detect ctDNA and rRNA in vitro and light up the nucleus in vivo depending on the intermolecular binding affinity. This AIE process enables the quantitative analysis or visualization of nucleic acids in solution or gels state, respectively. Furthermore, confocal laser scanning microscopy (CLSM) images of L929 cells stained with TPE-dC or TPE-dU clearly shows that nucleoside-based AIEgens bio-probes can pass the cell membranes to reach the cell nucleus, without cytotoxicity at the imaging condition (incubation time > 12 h, and 10 μmol/L of concentration). Since the nucleus is rich in DNA/RNA, fluorescence turn-on mode has a great potential in nucleus imaging and clinical diagnosis.     

Hydrazide–Hydrazone Small Molecules as AIEgens: Illuminating Mitochondria in Cancer Cells

Aggregation-induced-emission luminogens (AIEgens) have gained considerable attention as interesting tools for several biomedical applications, especially for bioimaging due to their brightness and photostability. Numerous AIEgens have been developed for lighting up the subcellular organelles to understand their forms and functions not only healthy but also unhealthy states, such as in cancer cells. However, there is lack of easily synthesizable, biocompatible small molecules for illuminating mitochondria (powerhouses) inside cells. To address this issue, an easy and short synthesis of new biocompatible hydrazide–hydrazone-based small molecules with remarkable aggregation-induced emission (AIE) properties is described. These small-molecule AIEgens showed hitherto unobserved AIE properties due to dual intramolecular H-bonding confirmed by theoretical calculation, pH- and temperature-dependent fluorescence and X-ray crystallographic studies. Confocal microscopy showed that these AIEgens were internalized into the HeLa cervical cancer cells without showing any cytotoxicity. One of the AIEgens was tagged with a triphenylphosphine (TPP) moiety, which successfully localized in the mitochondria of HeLa cells in a selective way compared to L929 noncancerous fibroblast cells. These unique hydrazide–hydrazone-based biocompatible AIEgens can serve as powerful tools to illuminate multiple subcellular organelles to elucidate their forms and functions in cancer cells for next-generation biomedical applications.     

Structure-property relationship on aggregation-induced emission properties of simple azine-based AIEgens and its application in metal ions detection

In recent twenty years, aggregation-induced emission (AIE), due to its excellent application prospect, has aroused widespread interests. The development of novel and easy to make AIE luminogens (AIEgens) is an attractive subject. For this purpose, it's very important to study the structure-property relationship of AIEgens. Because azine derivatives are easy to synthesis and some of them have nice AIE properties, herein, a series of azine derivatives (ADs) were employed as models to study the influence of different functional groups, electronic effects and structures on the AIE properties of azine derivatives. The AIE mechanism were studied by single crystal analysis, density functional theory (DFT) calculations and so on. The results indicated that the o-hydroxyl aryl substituted azine compounds could show good AIE properties. Meanwhile, the AIE properties of o-hydroxyl aryl substituted azine compounds were also influenced by the electronic effects of the aryl groups in the azine compounds. The o-hydroxyl groups could form intramolecular hydrogen bond with imine group, which play key role to restrict the intramolecular rotation of the aryl groups and act as base stone for the AIE process of this kind compounds. The HOMO-LUMO energy gaps of o-hydroxyl substituted azine are smaller than other homologous compounds, which is agree with the proposed AIE mechanism. Finally, thanks to the AIE properties, the o-hydroxy-substituted azines could be used as efficient Al³⁺ and Cu²⁺ fluorescent chemosensors in different conditions. In addition, test strips based on AD10 has been prepared, which can conveniently detect Cu²⁺ in industrial wastewater. This research supplied a way for the design of novel easy to make AIEgens through simple azine derivatives.     

Immobilization of AIEgens into metal‐organic frameworks: Ligand design,emission behavior,and applications

Aggregation‐induced emission (AIE), in which the luminophores are highly emissive in aggregate state, is one of the most unique photophysical phenomena and has shown interesting applications in many areas. The immobilization of AIE luminogens (AIEgens) into metal‐organic frameworks (MOFs), which are inorganic‐organic hybrid porous materials with tunable and predictable structures, has been investigated over the past few years. These well‐defined porous frameworks cannot only provide an ideal platform for studying the mechanism of AIE phenomenon in solid state, but also show potential applications from sensing to white light‐emitting diodes. In this highlight, we will summarize the recent progress of AIEgens‐based MOFs, including ligand design, emission behavior, and applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1809–1817     

Aggregation-Induced Emission: Recent Advances in Materials and Biomedical Applications

The concept of aggregation-induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image-guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.     

Achieving highly efficient aggregation-induced emission,reversible and irreversible photochromism by heavy halogen-regulated photophysics and D–A molecular pattern-controlled photochemistry of through-space conjugated luminogens

It is extremely challenging but desirable to regulate the photophysical and photochemical processes of aggregation-induced emission luminogens (AIEgens) in distinct states in a controllable manner. Herein, we design two groups of AIEgens based on a triphenylacrylonitrile (TPAN) skeleton with through-space conjugation (TSC) property, demonstrate controlled regulation of photophysical emission efficiency/color and photochemical photochromic and photoactivatable fluorescence behaviours of these compounds, and further validate design principles to achieve highly efficient and emission-tuning AIEgens and to accomplish photo-dependent color switches and fluorescence changes. It is surprisingly found that the introduction of heavy halogens like bromine into a TPAN skeleton dramatically enhances the emission efficiency, and such an abnormal phenomenon against the heavy-atom effect is attributed to the specific through-space conjugation nature of the AIE-active skeleton, effective intermolecular halogen-bond-induced restriction of intramolecular motions, and heavy atom-induced vibration reduction. The incorporation of two electron-donating amino groups into the TPAN skeleton cause the luminogens to undergo a bathochromic shifted emission due to the formation of a D–A pattern. Apart from the regulation of photophysical processes in the solid state, the construction of the D–A pattern in luminogens also results in extremely different photochemical reactions accompanying reversible/irreversible photochromism and photoactivatable fluorescence phenomena in a dispersed state. It is revealed that photo-triggered cyclization and decyclization reactions dominantly contribute to reversible photochromism of the TPAN family, and the photo-induced cyclization–dehydrogenation reaction is responsible for the irreversible color changes and photoactivatable fluorescence behaviours of the NTPAN family. The demonstrations of multiple-mode signaling in photoswitchable patterning and information encryption highlight the importance of controlled regulation of photophysics and photochemistry of fused chromic and AIE-active luminogens in distinct states.

Highly efficient aggregation-induced emission, reversible and irreversible photochromism are achieved by regulating heavy halogen-regulated photophysics and D–A molecular pattern-controlled photochemistry of through-space conjugated luminogens.     

3,4,5-Triphenyl-1,2,4-triazole-based multifunctional n-type AIEgen

The luminogens with aggregation-induced emission (AIEgens) characteristics have been widely applied in diverse areas. However, the n-type AIEgens are to be further developed. In this paper, we designed and synthesized an n-type multifunctional AIEgen of tetraphenylethene-substituted 3,4,5-triphenyl-4H-1,2,4-triazole (BTPE-TAZ). This AIEgen can serve as both light-emitting and electron-transporting layers in organic light-emitting devices. Moreover, it also exhibits the interesting optical waveguide and reversible mechanochromic luminescence properties, which are of great potential for practical applications.     

Three-Pronged Attack by Homologous Far-red/NIR AIEgens to Achieve 1+1+1>3 Synergistic Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.     

State-crossing from a Locally Excited to an Electron Transfer State(SLEET) Model Rationalizing the Aggregation-induced Emission Mechanism of (Bi)piperidylanthracenes

Luminogens with aggregation-induced emission(AIE)characteristics(or AIEgens)have been widely used in various applications due to their excellent luminescent properties in molecular aggregates and the solid state.A deep understanding of the AIE mechanism is critical for the rational development of AIEgens.In this work,the“state-crossing from a locally excited to an electron transfer state”(SLEET)model is employed to rationalize the AIE phenomenon of two(bi)piperidylanthracenes.According to the SLEET model,an electron transfer(ET)state is formed along with the rotation of the piperidyl group in the excited state of(bi)piperidylan-thracene monomers,leading to fluorescence quenching.In contrast,a bright state exists in the crystal and molecular aggregates of these compounds,as the intermolecular interactions restrict the formation of the dark ET state.This mechanistic understanding could inspire the deployment of the SLEET model in the rational designs of various functional AIEgens.     

Nonconventional macromolecular luminogens with aggregation-induced emission characteristics

Nonconventional luminogens without classic conjugated structures have drawn increasing interests owing to their fundamental importance and promising applications. These luminogens generally bear such subgroups as tertiary amine, C = C, C≡N, C = O, OH, ether, and imide. The emission mechanism, however, remains under debate. Different assumptions like oxidation or acidification of tertiary amines, aggregation of C = O groups, as well as clustering and electron cloud overlap are proposed. Unlike concentration quenching and aggregation-caused quenching (ACQ) that are normally observed in traditional luminogens, many of these unorthodox luminogens exhibit unique aggregation-induced emission (AIE) characteristics, regardless of their molecular architectures. This review summarizes varying unorthodox luminogens with AIE features, aiming to outline the recent advances in this exciting area, with focus on the macromolecular systems. In light of the reported results, clustering-triggered emission mechanism, namely clustering of diverse subgroups with subsequent electron cloud overlap and conformation rigidification can well rationalize the photophysical behaviors of most systems. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 560–574