Photoactivation of Solid-State Fluorescence through Controllable Intermolecular [2+2] Photodimerization.

Intermolecular [2+2] photodimerization provides a distinctive approach to construct photoresponsive fluorescent materials in a manner of switching on solid-state fluorescence. Herein, we report efficient photoactivation of bright solid-state fluorescence based on controllable intermolecular [2+2] photodimerization reaction of benzo[b]thiophene 1,1-dioxide (BTO) derivatives, which provides a simple and effective way to construct smart photoresponsive solid-state fluorescent materials. Rational choice of substituents in BTO molecular skeleton enables them to efficiently undergo photodimerization through regulating molecular stacking in crystal, and also leads to photoactivation of solid-state fluorescence due to the generation of brightly fluorescent photodimers. This intermolecular photodimerization reaction also offers an effective method to synthesize photostable AIEgens with purely through-space conjugation.

A novel fluorescence aptasensor based on PCN-223 as an efficient quencher for sensitive determination of prostate-specific antigen.

A novel fluorescence aptasensor based on PCN-223 as an efficient quencher was developed to sensitively detect prostate-specific antigen (PSA). The 5-carboxytetramethylrhodamine (TAMRA)-labeled PSA aptamer was adsorbed on PCN-223 by π-π stacking and hydrogen-bonding interactions, which contributed to fluorescence quenching because of the photoinduced electron transfer from TAMRA to PCN-223. In addition, the amount of quenched fluorescence of the PSA-binding aptamer complex-PCN-223 was lower than that of TAMRA aptamer-PCN-223 without PSA (at excitation/emission peaks of 545/582 nm), which can be explained by the fact that the PSA-binding aptamer complexes contributed to the separation of the aptamer from PCN-223. ∆F value of fluorescence intensities for TAMRA aptamer-PCN-223 with and without PSA showed a good linear relationship with PSA concentration over a range of 0.1 to 24 ng mL-1, with a detection limit of 0.05 ng mL-1. Compared with three metal-organic frameworks (MOFs) of UiO-66-NH2, ZIF-67, and Ni3(HITP)2 as quenchers, PCN-223 as a Zr-MOF exhibited the highest ∆F value for PSA detection. The advantage of PCN-223 could be attributed to its carboxyl, benzene, and porphyrin groups, the large specific surface area and good biocompatibility. This proposed aptasensor can be successfully used to detect PSA in sera of prostate cancer patients. The PSA detection results of this aptasensor were consistent with those which were obtained from hospital by Archtecti2000sr automatic chemiluminescence immunoanalyzer. The proposed aptasensor has potential clinical detection application.

Novel Aggregation-Enhanced PEC Photosensitizer Based on Electrostatic Linkage of Ionic Liquid with Protoporphyrin IX for Ultrasensitive Detection of Molt-4 Cells.

Nowadays, aggregation quenching of most organic photosensitizers in aqueous media seriously restricts analytical and biomedical applications of photoelectrochemical (PEC) sensors. In this work, an aggregation-enhanced PEC photosensitizer was prepared by electrostatically bonding protoporphyrin IX (PPIX) with an ionic liquid of 1-butyl-3-methylimidazole tetrafluoroborate ([BMIm][BF4]), termed as PPIX-[BMIm] for clarity. The resultant PPIX-[BMIm] showed weak photocurrent in pure dimethyl sulfoxide (DMSO, good solvent), while the PEC signals displayed a 44.1-fold enhancement in a water (poor solvent)/DMSO binary solvent with a water fraction (fw) of 90%. Such PEC-enhanced mechanism was critically studied by electrochemistry and density functional theory (DFT) calculation in some detail. Afterward, a label-free PEC cytosensor was built for ultrasensitive bioassay of acute lymphoblastic leukemia (molt-4) cells by electrodepositing Au nanoparticles (Au NPs) on the PPIX-[BMIm] aggregates and sequential assembly of protein tyrosine kinase (PTK) aptamer DNA (aptDNA). The resultant cytosensor showed a wide linear range (300 to 3 × 105 cells mL-1) with a limit of detection (LOD) as low as 63 cells mL-1. The aggregation-enhanced PEC performance offers a valuable and practical pathway for synthesis of advanced organic photosensitizer to explore its PEC applications in early diagnosis of tumors.

Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe.

Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca2+ by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells.

Antipermeability Strategy to Achieve Extremely High Specificity and Ultralong Imaging of Diverse Cell Membranes Based on Restriction-Induced Emission of AIEgens.

Long-term in situ cell membrane-targeted bioimaging is of great significance for studying specific biological processes and functions, but currently developed membrane probes are rarely simultaneously used to image the plasma membrane of animal and plant cells, and these probes lack sufficiently high long-term targeting ability. Herein, we proposed an antipermeability strategy to achieve highly specific and long-term imaging of plasma membranes of both human and plant cells using the steric hindrance effect and restriction-induced emission of AIE-active probes based on an updated membrane model. A certain degree of rigidity of plasma membrane containing a large ratio of rigid cholesterol molecules in the updated membrane model provides a promising opportunity to design antipermeable probes by introducing a rigid steric hindrance group in the probe. The designed antipermeable probes can anchor inside plasma membrane for a long term relying on the combination of the steric hindrance effect and the electrostatic and hydrophobic interactions between the probe and the membrane, as well as light up the membrane via the restriction-induced emission mechanism. The excellent performance in imaging completeness and specificity for both human cells and plant cells clearly shows that these designed probes possess outstanding antipermeability to achieve long-term specific imaging of membrane. These probes also show some advanced features such as ultrafast staining, wash-free merit, favorable biocompatibility, good photostability, and effective resistance to viscosity and pH alteration. This work also provides a valuable design principle for membrane probes of plant cells that the designed probes require a suitable molecular size favoring the penetration of small pores of cell walls.

Photochemically Enhanced Emission by Introducing Rational Photoactive Subunits into an Aggregation-Induced Emission Luminogen.

Herein, we propose a rational design strategy by introducing photoactive thienyl and pyridyl groups into an AIE-active tetraarylethene skeleton to achieve highly efficient photochemistry-activated fluorescence enhancement from dominantly photo-physical aggregation-induced emission behavior, and prove that such photoactivated fluorescence enhancement is perfectly suited for superstable photocontrollable dual-mode patterning applications in both solution and solid matrix. It is found that the photoactivated fluorescence of designed AIEgen is attributed to the irreversible cyclized-dehydrogenation reaction under UV irradiation, and the oxidation product has a brighter fluorescence in both solution and solid states owning to its rigid and planar structure. The overall transformation rate of the AIEgen from its opened form to dehydrogenated form is up to nearly 100 % in a short period of UV irradiation, and the fast transformation and the stable product of this photochemical reaction guarantees super stability of photocontrolled patterning, which can be applied in photoactivated dual-mode patterning and advanced anti-counterfeiting.

Photophysical Switching between Aggregation-Induced Phosphorescence and Dual-State Emission by Isomeric Substitution.

It is attractive but highly challenging to achieve controllable regulation of photophysical properties of pure organic luminogens, due to distinct work mechanisms and molecular structures. Here, a strategy to regulate in a controllable way the emission behavior of luminogens is reported, according to which long-lived aggregation-induced emission (AIE) can be switched to short-lived dual-state emission (DSE) by an isomer-based substitution reaction. Three luminogens with sharply different photophysical behaviors, including aggregation-induced phosphorescence and dual-state fluorescence emission, were obtained through a substitution reaction with three isomers. Freely rotating structures are attributed to aggregation-induced phosphorescence behavior, whereas twisted rigidification of the molecule greatly contributes to its dual-state emission phenomenon. This work contributes to the controlled regulation of photophysical behaviors through simple reactions and provides a solid evidence to support the key role of the prohibition of intramolecular rotation in aggregation-induced emission process and molecular design of dual-state emitters.

Rational Design of Dual-State Emission Luminogens with Solvatochromism by Combining a Partially Shared Donor-Acceptor Pattern and Twisted Structures.

We report a general design strategy for a new class of luminogens with dual-state emission (DSEgens) that are brightly emissive in both the solution and solid state, with solvatochromism properties, by constructing a partially shared donor-acceptor pattern based on a twisted molecule. The DSEgens with bright fluorescence emission in both the solid and solution state demonstrate a unique solvatochromism behaviour depending on solvent polarity and thus may have applications in anti-counterfeiting.

Thiol-ene click reaction-induced fluorescence enhancement by altering the radiative rate for assaying butyrylcholinesterase activity.

Butyrylcholinesterase (BChE) generally acts as an important plasma biomarker for clinical diagnosis due to its major contribution to human plasma cholinesterase levels, but its current fluorometric assay relying on fluorogenic substrates frequently suffers from the lack of sufficiently fast response time and specific recognition of substrates relative to the traditional Ellman's method. In this work, we report a fluorescent molecular probe for assaying BChE activity based on thiol-triggered fluorescence enhancement via thiol-ene click reactions. A low-temperature experiment and theoretical analysis exclude the possibility of weak fluorescence of the probe caused by an intramolecular photoinduced electron transfer process and support the main cause of an ultraslow radiative rate due to the introduction of two acrylyl groups. This probe has sensitive fluorescence responses to thiols via thiol-ene click chemistry, and it can distinguish between glutathione and cysteine or homocysteine in different emission colors. The rapid reaction kinetics of this probe enables it to monitor hydrolysis reactions catalyzed by butyrylcholinesterase (BChE) in a real-time manner. This probe is used to develop the first fluorometric assay of BChE activity based on fluorescence enhancement triggered by thiol-ene click chemistry using butyrylthiocholine as the substrate. The established BChE assay shows excellent sensitivity, and is capable of avoiding the interference from glutathione and acetylcholinesterase (AChE) in a complex matrix. The inhibition test of tacrine on BChE with this assay substantiates its feasibility in screening potential inhibitors of BChE. This work demonstrates a design strategy of fluorescent probes lighted up by thiol-ene click reactions, reveals the main cause of thiol-triggered fluorescence enhancement by altering the radiative rate, and provides the first fluorometric assay of BChE based on rapid thiol-ene click reactions.

Viscosity-sensitive thiolated gold nanoclusters with diffusion-controlled emission for intracellular viscosity imaging.

A unique diffusion-dependent emission phenomenon of gold nanoclusters was discovered, and can be regulated by the variation in viscosity and temperature. This specific property of gold nanoclusters was further used for viscosity monitoring in live cells, and the results demonstrated that gold nanoclusters are capable of real-time monitoring the abnormal viscosity change inside the cells.

Redox-Controlled Fluorescent Nanoswitch Based on Reversible Disulfide and Its Application in Butyrylcholinesterase Activity Assay.

Butyrylcholinesterase (BChE) mainly contributing to plasma cholinesterase activity is an important indicator for routinely diagnosing liver function and organophosphorus poisoning in clinical diagnosis, but its current assays are scarce and frequently suffer from some significant interference and instability. Herein, we report a redox-controlled fluorescence nanoswtich based on reversible disulfide bonds, and further develop a fluorometric assay of BChE via thiol-triggered disaggregation-induced emission. Thiol-functionalized carbon quantum dots (thiol-CQDs) with intense fluorescence is found to be responsive to hydrogen peroxide, and their redox reaction transforms thiol-CQDs to nonfluorescent thiol-CQD assembly. The thiols inverse this process by a thiol-exchange reaction to turn on the fluorescence. The fluorescence can be reversibly switched by the formation and breaking of disulfide bonds caused by external redox stimuli. The specific thiol-triggered disaggregation-induced emission enables us to assay BChE activity in a fluorescence turn-on and real-time way using butyrylthiocholine iodide as the substrate. As-established BChE assay achieves sufficient sensitivity for practical determination in human serum, and is capable of avoiding the interference from micromolar glutathione and discriminatively quantifying BChE from its sister enzyme acetylcholinesterase. The first design of reversible redox-controlled nanosiwtch based on disulfide expands the application of disulfide chemistry in sensing and clinical diagnostics, and this novel BChE assay enriches the detection methods for cholinesterase activity.

Reversible Switching between Phosphorescence and Fluorescence in a Unimolecular System Controlled by External Stimuli.

Manipulation of the emission properties of pure organic molecules through external stimuli is attractive but challenging. Herein, a dual-emissive hexathiobenzene-based molecule is reported with significant aggregation-induced phosphorescence characteristics, and demonstrates reversible switching among blue, green, and yellow phosphorescence by controlling molecular aggregation state or protonation state. Variation of solvent or pH value manipulates the interconversion between fluorescence and phosphorescence, while the change in protonation state in organic solvent switches two short-lived emissions in a controllable manner. Such a controlled manipulation is achieved by the rational design of combining a twisted structure and the proper arrangement of energy gaps among different excited states. This work provides a new design principle for organic molecules with efficient room-temperature phosphorescence and tunable singlet-triplet emissive properties, and contributes to the design and development of smart materials and intelligent optoelectronic devices.

Functional Carbon Quantum Dots: A Versatile Platform for Chemosensing and Biosensing.

Carbon quantum dot has emerged as a new promising fluorescent nanomaterial due to its excellent optical properties, outstanding biocompatibility and accessible fabrication methods, and has shown huge application perspective in a variety of areas, especially in chemosensing and biosensing applications. In this personal account, we give a brief overview of carbon quantum dots from its origin and preparation methods, present some advance on fluorescence origin of carbon quantum dots, and focus on development of chemosensors and biosensors based on functional carbon quantum dots. Comprehensive advances on functional carbon quantum dots as a versatile platform for sensing from our group are included and summarized as well as some typical examples from the other groups. The biosensing applications of functional carbon quantum dots are highlighted from selective assays of enzyme activity to fluorescent identification of cancer cells and bacteria.

Intermolecular Oxidative Radical Addition to Aromatic Aldehydes: Direct Access to 1,4- and 1,5-Diketones via Silver-Catalyzed Ring-Opening Acylation of Cyclopropanols and Cyclobutanols.

A novel silver-catalyzed ring-opening acylation of cyclopropanols and cyclobutanols is described. The reaction proceeds under mild and neutral conditions and provides a facile access to nonsymmetric 1,4- and 1,5-diketones in promising yields with broad substrate scope. Mechanistic studies including DFT calculations suggest the involvement of an uncommon water-assisted 1,2-HAT process, which is strongly exothermic and thus promotes addition of carbon radicals to aldehydes. In contrast to traditional reductive radical addition protocols, this work represents the first example of the intermolecular oxidative radical addition to aldehydes, thus offering a novel strategy for the direct synthesis of acyclic ketones from readily accessible aldehydes.

Reversible Luminescent Nanoswitches Based on Aggregation-Induced Emission Enhancement of Silver Nanoclusters for Luminescence Turn-on Assay of Inorganic Pyrophosphatase Activity.

Unique aggregation-induced emission (AIE) property has been found and widely applied in chemo/biosensors for thiolated gold nanoclusters and copper nanoclusters; however, little is known about this property of thiolate-protected silver nanoclusters. In this work, specific aggregation-induced emission enhancement (AIEE) of glutathione-capped silver nanoclusters (AgNCs) was verified via its solid-state luminescence and enhanced emission in poor solvent, three stimuli responsive nanoswitches were constructed based on its AIEE property, and a reliable and sensitive PPase assay was developed via ion-triggered luminescence switch. Glutathione-capped AgNCs from a facile one-pot synthesis were found to possess bright red luminescence and aggregation-induced emission enhancement property. This AIEE feature enables AgNCs in sensitive response to pH and temperature in a reversible way, allowing the two nanoswitches to precisely monitor the change of environmental pH and temperature. Complexation reactions among AgNCs, aluminum cation and PPi were also designed for an ion-triggered luminescence nanoswitch, which allows selective response to aluminum cation or PPi in luminescence. This ion-driven luminescence switch is further utilized to design a novel detection strategy for PPase activity through competitive coordination reactions. Our method illustrates a novel detection strategy mediated by complexation reaction between Al3+ and AgNCs avoiding the involvement of copper cations in the detection, and this developed assay performed well in detection of PPase level in fresh rat serum. This work confirms unique aggregation-induced emission enhancement property of glutathione-capped AgNCs, constructs multiple luminescence switches based on its multistimuli responsive behaviors, and demonstrates an example of Al3+-mediated detection strategy for PPase assay.

Bonding-induced emission of silyl-protected copper nanoclusters for luminescence turn-on detection of trace water in organic solvents.

A novel bonding-induced emission (BIE) phenomenon of silyl-protected copper nanoclusters was observed and identified, and a new detection method for trace water in organic solvents was established based on a water-triggered BIE process. This assay employs simple and commercially available reagents and is capable of determining trace water at the ppm level.

Luminescent Nanoswitch Based on Organic-Phase Copper Nanoclusters for Sensitive Detection of Trace Amount of Water in Organic Solvents.

Brightly luminescent copper nanoclusters (CuNCs) were prepared via a facile one-step synthesis in organic phase, and a novel luminescent nanoswitch on the basis of CuNCs through alternation of the physical states between aggregation and dispersion in response to specific external stimuli was designed. Two states including aggregation state and disaggregation state corresponding to fluorescence on and off signaling can be readily switched in a reversible way based on the aggregation-induced emission and disaggregation-induced quenching mechanism, respectively. This reversible nanoswitch can be controlled by the external stimulus water or N,N'-dicyclohexylcarbodiimide (DCC). The bright luminescence due to aggregation of CuNCs in organic solvents can be effectively quenched by the introduction of a small amount of water, where a disaggregation-induced quenching takes place. This specific behavior is capable to quantify an ultralow level (ppm) of water in aprotic solvents. The excellent reversibility of the nanoswitch enables one to monitor water content in a continuous and recyclable way.

Luminescent Aggregated Copper Nanoclusters Nanoswitch Controlled by Hydrophobic Interaction for Real-Time Monitoring of Acid Phosphatase Activity.

A reversible luminescence nanoswitch through competitive hydrophobic interaction among copper nanoclusters, p-nitrophenol and α-cyclodextrin is established, and a reliable real-time luminescent assay for acid phosphatase (ACP) activity is developed on the basis of this luminescence nanoswitch. Stable and intensely luminescent copper nanoclusters (CuNCs) were synthesized via a green one-pot approach. The hydrophobic nature of CuNCs aggregate surface is identified, and further used to drive the adsorption of p-nitrophenol on the surface of CuNCs aggregate due to their hydrophobic interaction. This close contact switches off the luminescence of CuNCs aggregate through static quenching mechanism. However, the introduction of α-cyclodextrin switches on the luminescence since stronger host-guest interaction between α-cyclodextrin and p-nitrophenol causes the removal of p-nitrophenol from the surface of CuNCs. This nanoswitch in response to external stimulus p-nitrophenol or α-cyclodextrin can be run in a reversible way. Luminescence quenching by p-nitrophenol is further utilized to develop ACP assay using p-nitrophenyl phosphate ester as the substrate. Quantitative measurement of ACP level with a low detection limit of 1.3 U/L was achieved based on this specific detection strategy. This work reports a luminescence nanoswitch mediated by hydrophobic interaction, and provides a sensitive detection method for ACP level which is capable for practical detection in human serum and seminal plasma.

Carbon quantum dots-based recyclable real-time fluorescence assay for alkaline phosphatase with adenosine triphosphate as substrate.

A convenient, reliable, and highly sensitive real-time assay for alkaline phosphatase (ALP) activity in the continuous and recyclable way is established on the basis of aggregation and disaggregation of carbon quantum dots (CQDs) through the competitive assay approach. CQDs and adenosine triphosphate (ATP) were used as the fluorescent indicator and substrate for ALP activity assessment, respectively. Richness of carboxyl groups on the surface of CQDs enables their severe aggregation triggered by cerium ions, which results in effective fluorescence quenching. Under the catalytic hydrolysis of ALP, ATP can be rapidly transformed to phosphate ions. Stronger affinity of phosphate ions to cerium ions than carboxyl groups is taken advantage of to achieve fluorescence recovery induced by redispersion of CQDs in the presence of ALP and ATP. Quantitative evaluation of ALP activity in a broad range from 4.6 to 383.3 U/L with the detection limit of 1.4 U/L can be realized in this way, which endows the assay with high enough sensitivity for practical detection in human serum. The assay can be used in a recyclable way for more than three times since the generated product CePO4 as a precipitate can be easily removed from the standard assay system. This strategy broadens the sensing application of fluorescent CQDs with excellent biocompatibility and provides an example based on disaggregation in optical probe development.

Reversible Fluorescent Nanoswitch Based on Carbon Quantum Dots Nanoassembly for Real-Time Acid Phosphatase Activity Monitoring.

A reversible fluorescence nanoswitch by integrating carbon quantum dots nanoassembly and pyrophosphate ion is developed, and a reliable real-time fluorescent assay for acid phosphatase (ACP) activity is established on the basis of the fluorescence nanoswitch. Carbon quantum dots (CQDs) abundant in carboxyl groups on the surface, nickel(II) ion and pyrophosphate ion comprise the fluorescent nanoswitch, which operates in the following way: the nanoassembly consisting of CQDs and nickel ions can be triggered by pyrophosphate ion serving as an external stimulus. At the same time, the fluorescence nanoswitch switches between two fluorescence states (OFF and ON) accompanying shifts in their physical states aggregation and disaggregation. Based on the nanoswitch, the introduction of ACP leads to breakdown of pyrophosphate ions into phosphate ions and resultant fluorescence quenching due to catalytic hydrolysis of ACP toward pyrophosphate ions (PPi). Quantitative evaluation of ACP activity in a broad range from 18.2 U/L to 1300 U/L, with a detection limit of 5.5 U/L, can be achieved in this way, which endows the assay with sufficiently high sensitivity for practical detection in human serum and seminal plasma.