Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

Formamidinium Lead Iodide-Based Inverted Perovskite Solar Cells with Efficiency over 25 % Enabled by An Amphiphilic Molecular Hole-Transporter.

Formamidinium lead iodide (FAPbI3) represents an optimal absorber material in perovskite solar cells (PSCs), while the application of FAPbI3 in inverted-structured PSCs has yet to be successful, mainly owing to its inferior film-forming on hydrophobic or defective hole-transporting substrates. Herein, we report a substantial improvement of FAPbI3-based inverted PSCs, which is realized by a multifunctional amphiphilic molecular hole-transporter, (2-(4-(10H-phenothiazin-10-yl)phenyl)-1-cyanovinyl)phosphonic acid (PTZ-CPA). The phenothiazine (PTZ) based PTZ-CPA, carrying a cyanovinyl phosphonic acid (CPA) group, forms a superwetting hole-selective underlayer that enables facile deposition of high-quality FAPbI3 thin films. Compared to a previously established carbazole-based hole-selective material (2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl)phosphonic acid (MeO-2PACz), the crystallinity of FAPbI3 is enhanced and the electronic defects are passivated by the PTZ-CPA more effectively, resulting in remarkable increases in photoluminescence quantum yield (four-fold) and Shockley-Read-Hall lifetime (eight-fold). Moreover, the PTZ-CPA shows a larger molecular dipole moment and improved energy level alignment with FAPbI3, benefiting the interfacial hole-collection. Consequently, FAPbI3-based inverted PSCs achieve an unprecedented efficiency of 25.35 % under simulated air mass 1.5 (AM1.5) sunlight. The PTZ-CPA based device shows commendable long-term stability, maintaining over 90 % of its initial efficiency after continuous operation at 40 °C for 2000 hours.

Efficient Visible-Light-Activated Ultra-Long Room-Temperature Phosphorescence Triggered by Multi-Esterification.

The development of ultra-long room-temperature phosphorescence (UL-RTP) in processable amorphous organic materials is highly desirable for applications in flexible displays, anti-counterfeiting, and bio-imaging. However, achieving efficient UL-RTP from amorphous materials remains a challenging task, especially with activation by visible light and a bright afterglow. Here we report a general and rational molecular-design strategy to enable efficient visible-light-excited UL-RTP by multi-esterification of a rigid large-plane phosphorescence core. Notably, multi-esterification minimizes the aggregation-induced quenching and accomplishes a 'four birds with one stone' possibility in the generation and radiation process of UL-RTP: i) shifting the excitation from ultraviolet light to blue-light through enhancing the transition dipole moment of low-lying singlet-states, ii) facilitating the intersystem crossing process through the incorporation of lone-pair electrons, iii) boosting the decay process of long-lived triplet excitons resulting from a significantly increased transition dipole moment, and iv) reducing the intrinsic triplet nonradiative decay by substitution of high-frequency vibrating hydrogen atoms. All these factors synergistically contribute to the most efficient and stable visible-light-stimulated UL-RTP (lifetime up to 2.01 s and efficiency up to 35.4 % upon excitation at 450 nm) in flexible films using multi-esterified coronene, which allows high-tech applications in single-component time-delayed white light-emitting diodes and information technology based on flashlight-activated afterglow encryption.

Neglected acidity pitfall: boric acid-anchoring hole-selective contact for perovskite solar cells.

The spontaneous formation of self-assembly monolayer (SAM) on various substrates represents an effective strategy for interfacial engineering of optoelectronic devices. Hole-selective SAM is becoming popular among high-performance inverted perovskite solar cells (PSCs), but the presence of strong acidic anchors (such as -PO3H2) in state-of-the-art SAM is detrimental to device stability. Herein, we report for the first time that acidity-weakened boric acid can function as an alternative anchor to construct efficient SAM-based hole-selective contact (HSC) for PSCs. Theoretical calculations reveal that boric acid spontaneously chemisorbs onto indium tin oxide (ITO) surface with oxygen vacancies facilitating the adsorption progress. Spectroscopy and electrical measurements indicate that boric acid anchor significantly mitigates ITO corrosion. The excess boric acid containing molecules improves perovskite deposition and results in a coherent and well-passivated bottom interface, which boosts the fill factor (FF) performance for a variety of perovskite compositions. The optimal boric acid-anchoring HSC (MTPA-BA) can achieve power conversion efficiency close to 23% with a high FF of 85.2%. More importantly, the devices show improved stability: 90% of their initial efficiency is retained after 2400 h of storage (ISOS-D-1) or 400 h of operation (ISOS-L-1), which are 5-fold higher than those of phosphonic acid SAM-based devices. Acidity-weakened boric acid SAMs, which are friendly to ITO, exhibits well the great potential to improve the stability of the interface as well as the device.

Liquid Crystal Assembly for Ultra-dissymmetric Circularly Polarized Luminescence and Beyond.

Circularly polarized luminescence (CPL) is attracting much interest because it can carry extensive optical information. CPL shows left- or right-handedness and can be regarded as part of high-level visual perception to supply an extra dimension of information with regard to regular light. A key to meeting the needs for practical applications is to develop the emerging field of ultra-dissymmetric CPL. Chiral liquid crystal (LC) assemblies─otherwise referred to as cholesteric liquid crystals (CLCs)─are essentially organized helical superstructures with a highly ordered one-dimensional orientation, and distinctly superior to regular helical supramolecules. CLCs can achieve a perfect equilibrium of molecular short-range interaction and long-range orientational order, enabling molecule-scale chirality on a helical pitch and observable scale. LC assembly could be an ideal strategy for amplifying chirality, making it accessible to ultra-dissymmetric CPL. Herein, we focused on some basic but important issues regarding CPL: (i) How can CPL be created from chiral dyes? (ii) Is the chirality of luminescent dyes an essential factor for the generation of CPL? That is, can all chiral dyes emit CPL and vice versa? (iii) How can CPL be transferred within intermolecular systems, and what principles of CPL transmission should be followed? Given these queries and our work, in this Perspective we discuss the generation, transmission, and modulation of CPL with chiral LC assembly, aiming to design and build up novel chiroptical materials. Recent applications of CPL-active LC microstructures in three-dimensional displays, circularly polarized lasers, and asymmetric catalysis are also discussed.

Activatable BODIPY-chromene NIR-II probes with small spectral crosstalk enable high-contrast in vivo bioimaging.

Herein, we design a novel "crossbreeding" dye (BC-OH) within the second near-infrared (NIR-II) window based on BODIPY and chromene chromophores. BC-OH can serve as a platform to construct activatable NIR-II probes with small spectral crosstalk, thereby making a breakthrough in imaging in vivo H2O2 fluctuation in an APAP-induced liver injury model with high signal-to-background ratio.

Light-regulating chirality of metallacages featuring dithienylethene switches.

Dynamic chiral superstructures are of vital importance for understanding the organization and function of chirality in biological systems. However, achieving high conversion efficiency for photoswitches in nanoconfined architectures remains challenging but fascinating. Herein, we report a series of dynamic chiral photoswitches based on supramolecular metallacages through the coordination-driven self-assembly of dithienylethene (DTE) units and octahedral zinc ions, thereby successfully achieving an ultrahigh photoconversion yield of 91.3% in nanosized cavities with a stepwise isomerization mechanism. Interestingly, the chiral inequality phenomenon is observed in metallacages, resulting from the intrinsic photoresponsive chirality in the closed form of the dithienylethene unit. Upon hierarchical organization, we establish a dynamic chiral system at the supramolecular level, featuring chiral transfer, amplification, induction, and manipulation. This study provides an intriguing idea to simplify and understand chiral science.

Immobilizing Surface Halide in Perovskite Solar Cells via Calix[4]pyrrole.

Halide diffusion across the charge-transporting layer followed by a reaction with metal electrode represents a critical factor limiting the long-term stability of perovskite solar cells (PSCs). In this work, a supramolecular strategy with surface anion complexation is reported for enhancing the light and thermal stability of perovskite films, as well as devices. Calix[4]pyrrole (C[4]P) is demonstrated as a unique anion-binding agent for stabilizing the structure of perovskite by anchoring surface halides, which increases the activation energy for halide migration, thus effectively suppressing the halide-metal electrode reactions. The C[4]P-stabilized perovskite films preserve their initial morphology after ageing at 85 °C or under 1 sun illumination in humid air over 50 h, significantly outperforming the control samples. This strategy radically tackles the halide outward-diffusion issue without sacrificing charge extraction. Inverted-structured PSCs based on C[4]P modified formamidinium-cesium perovskite exhibit a champion power conversion efficiency of over 23%. The lifespans of unsealed PSCs are unprecedentedly prolonged from dozens of hours to over 2000 h under operation (ISOS-L-1) and 85 °C ageing (ISOS-D-2). When subjected to a harsher protocol of ISOS-L-2 with both light and thermal stresses, the C[4]P-based PSCs maintain 87% of original efficiency after ageing for 500 h.

Serum-Based Detection of Liver Pathology Using a Fluorogenic Alkaline Phosphatase Probe.

Development of "ultrahigh contrast" fluorogenic probes for trapping alkaline phosphatase (ALP) activities in human serum is highly desirable for clinical auxiliary diagnosis for hepatobiliary diseases. However, the intrinsic dilemma of incomplete ionization of intramolecular charge transfer (ICT)-based ALP fluorophores and autofluorescence interference of serum result in low sensitivity and accuracy. Given that unique halogen effects could lead to a drastic decrease in the pKa value and a significant enhancement in the fluorescence quantum yield, herein we report an enzyme-activatable near-infrared probe based on a difluoro-substituted dicyanomethylene-4H-chromenep for achieving fluorescent quantification of human serum ALP. Rational design strategy is demonstrated by altering the substituted halogen groups to well regulate the pKa for meeting the physiological precondition. Owing to the complete ionization at pH 7.4 with tremendous fluorescence enhancement, the difluoro-substituted DCM-2F-HP manifests a linear relationship between the emission intensity and ALP concentration in both solution and serum samples. Along with measuring 77 human serum samples, the DCM-2F-HP based fluorescence method not only exhibits significant correlations with clinical colorimetry, but also distinguishes ALP patients from healthy volunteers, as well as assessing the progress of liver disease, thus providing a potential toolbox for quantitatively detecting ALP and warning the stage of hepatopathy.

[Direct determination of five xanthic acids in water by ultra performance liquid chromatography-tandem mass spectrometry].

Xanthates with different alkyl groups, such as ethyl, propyl, butyl, and amyl groups, are widely used in large quantities in the mining flotation of metallic minerals. Xanthates enter environmental waters through mineral processing wastewater discharge and are ionized or hydrolyzed into ions or molecules of xanthic acids (XAs) in water. XAs endanger aquatic plants and animals, as well as human health. To the best of our knowledge, XA analysis is mainly limited to butyl xanthate. Moreover, the isomers and congeners of XAs cannot be determined separately using the existing methods. Herein, a novel method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to separate and analyze five XAs, namely, ethyl-, isopropyl-, n-butyl-, isobutyl-, and amyl-XAs, in water. Water samples were filtered through a 0.22 µm hydrophilic polytetrafluoroethylene (PTFE) membrane and directly injected into the UPLC-MS/MS instrument. Separation was performed using a Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) with ammonia solution (pH 11)-acetonitrile (9∶1, v/v) as the mobile phase for isocratic elution. The five XAs were detected in the negative electrospray ionization (ESI-) and multiple reaction monitoring (MRM) modes. An internal standard method was used for quantification. The pretreatment and UPLC-MS/MS conditions were comprehensively optimized to achieve the separation and analysis of the five XAs via direct injection. The XAs showed negligible adsorption on hydrophobic PTFE, hydrophilic PTFE, hydrophilic polypropylene, and polypropylene membranes during filtration. However, the amyl-XA showed obvious adsorption on nylon and polyether sulfone membranes. The five XAs mainly formed [M-H]- parent ions in the ESI- mode and the main daughter ions obtained following collisional fragmentation depended on the alkyl groups of the XAs. Increasing the pH of the ammonia solution in the mobile phase to 11 led to the isomeric separation of n-butyl- and isobutyl-XAs. The optimized mobile phase inhibited the tailing of the chromatographic peak of amyl-XA and effectively improved all the chromatographic peak shapes of XAs. The BEH C18 column was selected as the chromatographic column owing to its better compatibility with high-pH solutions compared with the T3 C18 column. Preservation experiments conducted over 8 d showed that the concentration of all five XAs decreased over time at room temperature; among the XAs analyzed, the concentration of ethyl-XA revealed the most significant decrease. However, the recoveries of the five XAs at 4 and -20 ℃ remained high, ranging from 101% to 105% and from 100% to 106%, respectively, on the 8th day. The preservation observed with a high concentration of XAs was similar to that found with a low concentration. The preservation time was extended to 8 days at pH 11 and 4 ℃ away from the light. No significant matrix effects were observed for the five XA samples in surface water and groundwater, but industrial sewage exerted obvious matrix inhibitory effects on ethyl- and isopropyl-XAs. Owing to the short retention times of ethyl- and isopropyl-XAs, the co-fluxed interferents in the industrial sewage depressed the MS signals. The five XAs showed good linearity in the range of 0.25-100 µg/L, with correlation coefficients greater than 0.9996. The method detection limits were as low as 0.03-0.04 µg/L, and the intra- and inter-day precisions were 1.3%-2.1% and 3.3%-4.1%, respectively. The recoveries obtained under low, medium, and high spiked levels (1.00, 20.0, 80.0 µg/L) were 96.9%-133%, 100%-107%, and 104%-112%, respectively. The corresponding RSDs were 2.1%-3.0%, 0.4%-1.9%, and 0.4%-1.6%, respectively. The optimized method was successfully applied to the analysis of XAs in surface water, groundwater, and industrial sewage. The method could separate and detect various congeners and isomers of XAs without the need for cumbersome pretreatment processes, and its advantages include smaller sample requirements, simpler operation, higher sensitivity, and longer preservation time. The proposed technique presents excellent application potential in XA environmental monitoring and water evaluation, and mineral flotation studies.

Bent-to-planar Si-rhodamines: a distinct rehybridization lights up NIR-II fluorescence for tracking nitric oxide in the Alzheimer's disease brain.

An ongoing revolution in fluorescence-based technologies has transformed the way we visualize and manipulate biological events. An enduring goal in this field is to explore high-performance fluorogenic scaffolds that show tunability and capability for in vivo analysis, especially for small-molecular near-infrared (NIR) fluorophores. We present a unique bent-to-planar rehybridization design strategy for NIR fluorogenic scaffolds, thus yielding a palette of switchable bent/planar Si-rhodamines that span from visible to NIR-II wavelengths. We demonstrate that the rehybridization of meso-nitrogen in this innovative NIR scaffold Cl-SiRhd results in flipping between the disruption and recovery of the polymethine π-electron system, thereby significantly altering the spectral wavelength with crosstalk-free responses. Using elaborately lighting-up NIR-II probes with ultra-large Stokes shifts (ca. 250 nm), we successfully achieve real-time in situ monitoring of biological events in live cells, zebrafish, and mice. Notably, for the first time, the light-up NIR-II probe makes a breakthrough in directly in situ tracking nitric oxide (NO) fluctuations in the brains of mice with Alzheimer's disease. This de novo bent-to-planar rehybridization strategy of NIR-II probes opens up exciting opportunities for expanding the in vivo imaging toolbox in both life science research and clinical applications.

Minimizing buried interfacial defects for efficient inverted perovskite solar cells.

Controlling the perovskite morphology and defects at the buried perovskite-substrate interface is challenging for inverted perovskite solar cells. In this work, we report an amphiphilic molecular hole transporter, (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid, that features a multifunctional cyanovinyl phosphonic acid group and forms a superwetting underlayer for perovskite deposition, which enables high-quality perovskite films with minimized defects at the buried interface. The resulting perovskite film has a photoluminescence quantum yield of 17% and a Shockley-Read-Hall lifetime of nearly 7 microseconds and achieved a certified power conversion efficiency (PCE) of 25.4% with an open-circuit voltage of 1.21 volts and a fill factor of 84.7%. In addition, 1-square centimeter cells and 10-square centimeter minimodules show PCEs of 23.4 and 22.0%, respectively. Encapsulated modules exhibited high stability under both operational and damp heat test conditions.

Preparation of near-infrared AIEgen-active fluorescent probes for mapping amyloid-ß plaques in brain tissues and living mice.

Fibrillar aggregates of the amyloid-ß protein (Aß) are the main component of the senile plaques found in brains of patients with Alzheimer's disease (AD). Development of probes allowing the noninvasive and high-fidelity mapping of Aß plaques in vivo is critical for AD early detection, drug screening and biomedical research. QM-FN-SO3 (quinoline-malononitrile-thiophene-(dimethylamino)phenylsulfonate) is a near-infrared aggregation-induced-emission-active fluorescent probe capable of crossing the blood-brain barrier (BBB) and ultrasensitively lighting up Aß plaques in living mice. Herein, we describe detailed procedures for the two-stage synthesis of QM-FN-SO3 and its applications for mapping Aß plaques in brain tissues and living mice. Compared with commercial thioflavin (Th) derivatives ThT and ThS (the gold standard for detection of Aß aggregates) and other reported Aß plaque fluorescent probes, QM-FN-SO3 confers several advantages, such as long emission wavelength, large Stokes shift, ultrahigh sensitivity, good BBB penetrability and miscibility in aqueous biological media. The preparation of QM-FN-SO3 takes ~2 d, and the confocal imaging experiments for Aß plaque visualization, including the preparation for mouse brain sections, take ~7 d. Notably, acquisition and analyses for in vivo visualization of Aß plaques in mice can be completed within 1 h and require only a basic knowledge of spectroscopy and chemistry.

Overcoming C60-induced interfacial recombination in inverted perovskite solar cells by electron-transporting carborane.

Inverted perovskite solar cells still suffer from significant non-radiative recombination losses at the perovskite surface and across the perovskite/C60 interface, limiting the future development of perovskite-based single- and multi-junction photovoltaics. Therefore, more effective inter- or transport layers are urgently required. To tackle these recombination losses, we introduce ortho-carborane as an interlayer material that has a spherical molecular structure and a three-dimensional aromaticity. Based on a variety of experimental techniques, we show that ortho-carborane decorated with phenylamino groups effectively passivates the perovskite surface and essentially eliminates the non-radiative recombination loss across the perovskite/C60 interface with high thermal stability. We further demonstrate the potential of carborane as an electron transport material, facilitating electron extraction while blocking holes from the interface. The resulting inverted perovskite solar cells deliver a power conversion efficiency of over 23% with a low non-radiative voltage loss of 110 mV, and retain >97% of the initial efficiency after 400 h of maximum power point tracking. Overall, the designed carborane based interlayer simultaneously enables passivation, electron-transport and hole-blocking and paves the way toward more efficient and stable perovskite solar cells.

Tricyano-Methylene-Pyridine Based High-Performance Aggregation-Induced Emission Photosensitizer for Imaging and Photodynamic Therapy.

Photosensitizers equipped with high reactive oxygen species (ROS) generation capability and bright emission are essential for accurate tumor imaging and precise photodynamic therapy (PDT). However, traditional aggregation-caused quenching (ACQ) photosensitizers cannot simultaneously produce desirable ROS and bright fluorescence, resulting in poor image-guided therapy effect. Herein, we report an aggregation-induced emission (AIE) photosensitizer TCM-Ph with a strong donor-π-acceptor (D-π-A) structure, which greatly separates the HOMO-LUMO distribution and reduces the ΔEST, thereby increasing the number of triplet excitons and producing more ROS. The AIE photosensitizer TCM-Ph has bright near-infrared emission, as well as a higher ROS generation capacity than the commercial photosensitizers Bengal Rose (RB) and Chlorine e6 (Ce6), and can effectively eliminate cancer cells under image guidance. Therefore, the AIE photosensitizer TCM-Ph has great potential to replace the commercial photosensitizers.

Light-Reconfiguring Inhomogeneous Soft Helical Pitch with Fatigue Resistance and Reversibility.

Active engineering and modulation of optical spectra in a remote and fully reversible light is urgently desired in photonics, chemistry, and materials. However, the real-time regulation of multiple optical information such as wavelength, bandwidth, reflectance, and polarization is still a longstanding issue due to the lack of an appropriate photoresponsive candidate. Herein, we propose an additional "degree-of-freedom (DOF)" in a photo-modulated soft helix, and build up an unprecedented inhomogeneous helical pitch length with light-reconfiguring property, fatigue resistance, and reversibility. For the working model, the intrinsic chiral photoswitch LBC5 is employed as an actuator to modulate the helical pitch length, which is proportional to the irradiation intensity, and the unique broadband absorbance photo-modulator BTA-C5 is incorporated as an attenuator of the transmitted light to decrease its intensity along the sample thickness, therefore successfully adding another controlled DOF on the pitch length distribution (i.e., homogeneous or inhomogeneous) apart from the common soft helix with only a single DOF on the pitch length. The absorbance photo-modulator BTA-C5 with a unique variable broadband absorption enables the light to reconfigure the helical pitch from homogeneous to inhomogeneous, thereby achieving the robust fatigue-resistance establishment of reversible spectral programming. The established light-reconfigurable inhomogeneous helical pitch with the photoresponsive modulator BTA-C5 can provide a breakthrough to control absorbance and chirality, especially for dynamically broadening and narrowing the bandwidth on demand, and further enable the ever-desired broadband NIR circularly polarized luminescence (CPL) with a high dissymmetry factor glum of up to 1.88. The cutting-edge photoswitchable inhomogeneous soft helical pitch provides access to multi-freedom control in soft materials, optics, biophotonics, and other relevant fields.

Sterically Hindered Diarylethenes with a Benzobis(thiadiazole) Bridge: Enantiospecific Transformation and Reversible Photosuperstructures.

ConspectusPhotochromic diarylethenes featuring reversible regulation by external light irradiation have attracted increasing attention in versatile applications such as logic gates, supramolecular systems, liquid crystals, and super-resolution imaging because of their outstanding bistability and fatigue resistance. However, for typical diarylethene systems, there always exist three typical unsolved issues. The first is how to modulate the bistability between the open and closed forms from the viewpoint of ethene bridge aromaticity. The second is how to decrease and avoid the photoinactive parallel conformer in order to achieve a high quantum yield, since the open form possesses the photoactive antiparallel (ap) conformation and the photoinactive parallel (p) conformation. Because of the typical rapid rotation of the flexible side aryl groups, the two conformers cannot be separated efficiently, thereby resulting in a relatively low photocyclization quantum yield. The third is how to fulfill the enantiospecific transformation with reversibility to photomodulate the chirality. Stereochemically, the ap conformer with C2 symmetry can be further subdivided into a pair of enantiomers with P and M helicity originating from the central hexatriene moiety. Similarly, the rapid rotation can also lead to the loss of intrinsic chirality, restricting the development and application of light-driven chiroptical switches. Accordingly, it is desirable to construct a specific diarylethene system to break through these bottlenecks for real versatile applications.Our group has recently developed a unique sterically hindered diarylethene system based on benzobis(thiadiazole) as the ethene bridge for completely solving these issues. We introduce a low-aromaticity benzobis(thiadiazole) unit into the diarylethene as a central ethene bridge with incomparably high bistability. To block or freeze the rotation of flexible side aryls, we further incorporate a large bulky benzothiophene unit to induce a large steric hindrance, or rotation barrier, between the ethene bridge and side aryls, thereby successfully separating multiple conformers of the diarylethenes with high photocyclization quantum yields and enantiospecific photoreaction. Consequently, given such a fantastic building block, we enhance its performance by means of supramolecular self-assembly, thereby realizing unique conformer-dependent self-assembly as well as unprecedented concerted isomerization and enantiospecific photoreaction of photoresponsive metallacycles. In addition, decoration of the intrinsically chiral diarylethenes with mesogenic units can enable us to manipulate the helical superstructure of liquid crystals, thus achieving a multiple anticounterfeiting technique and a quadridimensional manipulable laser. We also unravel the dual aggregation-induced emission (AIE) behavior of the sterically hindered diarylethene, especially as applied in super-resolution imaging.

A pH-activated fluorescent probe via transformation of azo and hydrazone forms for lysosomal pH imaging.

We developed a fluorescent probe Sth-NH by introducing a 6-hydroxypyridone skeleton. The presence of an active proton enables the probe to transform from a deprotonated azo form to a hydrazone form in a strongly acidic environment to realize fluorescence light-up behavior, thus monitoring the lower lysosomal pH of cancer cells and distinguishing them from normal cells.

An AIE-active probe for monitoring calcium-rich biological environment with high signal-to-noise and long-term retention in situ.

Fluorescent probe is a first-line method for qualitative and quantitative detection of calcium ions (Ca2+) in organisms. However, the high affinity and aggregate-caused quenching (ACQ) characteristics of commercially available probes have restricted the detection limit to low concentrations from nM to µM, unavailable to detect higher Ca2+ concentrations from µM to mM in situ. Here, we develop a Ca2+ probe of TCM-4COOH with aggregation-induced emission (AIE) activity and desirable affinity, exhibiting a linear response to concentrated Ca2+ at mM level. The rapid binding between the TCM-4COOH and Ca2+ results in dramatic enhancement in fluorescence with high S/N ratio, and the nature that the chelates are not easy to diffuse from the cells endows the probe with long-term imaging ability in organisms. In the molecular design, the multiple iminodiacetic carboxyl groups ensure the good water solubility and pH biocompatibility of TCM-4COOH, resulting in negligible background fluorescence and high signal-to-noise (S/N) ratio. Moreover, the relatively dispersed carboxyl groups and the electron-withdrawing effect of TCM building block jointly adjust the probe affinity to Ca2+, thereby broadening the upper detection limit. In addition, to obtain better cell membrane penetrability, TCM-4COOH was modified with acetoxymethyl ester, which unit can be cleaved by endogenous esterase to release TCM-4COOH, so as to detect intracellular calcium ions. Benefit from the reasonable design of fluorophore and chelating groups, the AIE-active sensor TCM-4COOH can achieve long-term in-situ retention in visualizing calcium-overloaded cells and bone microcracks, especially providing a unique platform to broaden the upper limit of Ca2+ detection in biological environments.

Water-soluble bright NIR AIEgens with hybrid ROS for wash-free mitochondrial "off-on" imaging and photodynamic therapy.

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission (φF = 17.8%) and high hybrid ROS productivity (including OH˙ and 1O2).