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Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time (t1/2= 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical Xc–/GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (•OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic •OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivoantitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

Evaluating the correlation between hypoxia inducible factor 1 (HIF-1) and nitric oxide (NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet (LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe's capability of imaging exogenous and endogenous NO with specific in LDs of HepG2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situvisualization of NO-dependent HIF-1 upregulation through LD accumulation.

Glutathione (GSH)‐activated prodrugs are promising for overcoming the limitations of conventional anti‐tumor drugs. However, current GSH‐responsive disulfide groups exhibit unregulated reactivity, making it impossible to precisely control the drug release rate. We herein report a series of GSH‐responsive prodrugs with a “three‐in‐one” molecular design by integrating a fluorescence report unit, stimuli‐responsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution (SNAr) reactivity. The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron‐withdrawing or ‐donating abilities on the BODIPY core. Furthermore, the prodrugs self‐assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy (PDT). The PDT process also increases the concentration of GSH in cells, further promoting the release of drugs for chemotherapy. This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects. We report a series of GSH‐activated prodrugs with tunable drug release rates by the control of aromatic nucleophilic substitution (SNAr) reactivity. The prodrugs self‐assembled in water to form nanoparticles that serve as photosensitizers, allowing a sequential photodynamic‐chemo therapy in cancer cells.

“Aromatic nucleophilic substitution-rearrangement (SNAr-rearrangement)” mechanism provided a powerful tool to design fluorescent probes for the discrimination between biothiols.

Clarifying the signaling pathway associated with nitric oxide (NO) and glutathione (GSH) in cardiovascular disease therapy is important for understanding its physiological and pathological processes but is challenging due to the lack of efficient analytical techniques. Herein, we report a BODIPY-based fluorescent probe for recognition of NO and GSH in sequence with high sensitivity and selectivity. The probe exhibits turn-on fluorescence triggered by NO, followed by red-shifted emission in the presence of GSH. The sequentially activated mechanism allows the visualization of NO-induced GSH upregulation in drug-treated endothelial cells and zebrafish for the first time, revealing a signal pathway during the therapy. We hope that it can be used as a convenient and efficient tool for the study of the interplay between NO and GSH and for the screening of effective drugs for cardiovascular disease therapy.

Biothiols and SO2derivatives, as essential reactive sulfur species (RSS), play vital roles in various physiological processes and have a close network of generation and metabolic pathways among them. To clarify their complex correlations, fluorescent probes to simultaneously detect GSH, Cys, and SO2derivatives are highly desirable. Herein, we develop the first fluorescent probe (BO-HEM) to simultaneously discriminate GSH, Cys, and SO2derivatives. The fluorescent probe is designed by integration of hemicyanine and BODIPY fluorophores through an ether bond. The ether bond of the probe is rapidly replaced by thiolates through nucleophilic aromatic substitution (SNAr) to generate hemicyanine with NIR fluorescence and sulfur-BODIPY. The amino groups of Cys but not GSH then further replace the thiolate to form amino-BODIPY. As for SO32–, nucleophilic addition to the double bond of BO-HEMgenerates adduct O-BODIPYwith green fluorescence. To further improve the sensing performance, the nanoprobe with increased reactivity and biocompatibility is constructed by encapsulation of BO-HEMinto the polymeric micelle. More importantly, by taking advantage of the hydrophilicity of the reaction products, the spectral discrimination was further enhanced to avoid signal interference. The nanoprobe is applied to discriminate biothiols and SO2derivatives in living cells through three-color fluorescence imaging.

Aggregation-induced emission luminogens (AIEgens) have attracted increasing attention in recent years on account of their attribute of overcoming the aggregation-caused quenching (ACQ) phenomenon of conventional organic fluorophores. Despite their remarkable advantages and great developments, most organic AIEgens exhibit broad emission spectra with the full width at half-maxima (FWHM) over 100 nm, which is to the disadvantage of their practical applications. Herein, supramolecular polymeric AIE materials with brighter fluorescence and narrower emission band (higher color purity) than conventional AIEgens were developed by taking advantage of the light-harvesting strategy. These AIE materials, including nanoparticles, microfibers, and thin films, were fabricated from supramolecular polymers comprising quadruple hydrogen-bonded monomer tetraphenylethylene (TPE) and borondipyrromethene (BODIPY) as antenna chromophores and as energy acceptors, respectively. The excitation energy collected by TPE molecules was efficiently transferred to the BODIPY, resulting in up to 6-fold enhanced fluorescence intensity and narrowed emission band with FWHM decreasing from 148 to 32 nm. The resulting nanoparticles showed ∼5-fold higher brightness than commercial quantum dots. The highly fluorescent nanoparticles were successfully applied for in vitro and in vivo fluorescence and chemiluminescence imaging, showing superior imaging performance to conventional AIE nanoparticles.

Nitric oxide (NO) and glutathione (GSH) have interplaying roles in oxidant-antioxidant balance. In this work, we developed the first example of a single fluorescent probe that displayed a turn-on fluorescence response toward NO and GSH from dual emission channels. The probe was synthesized by introducing 4-amino-3-(methylamino)-phenol to a BODIPY scaffold. Specifically, the NO-mediated transformation of diamine into a triazole triggered the fluorescence in the green channel, and the GSH-induced SNAr substitution reaction led to the red-shifted emission in the red channel. The probe was successfully applied to detect the exogenous and endogenous NO and GSH in macrophage cells. More importantly, the probe revealed that NO induced by interferon-γ (IFN-γ), lipopolysaccharide (LPS), and l-arginine (l-Arg) could also elicit the augmentation of intracellular GSH. We anticipate the probe would hold great potential for investigating the redox balance in biological processes.

We reported a difluoroboron β-diketonate dye that displays bright red/NIR fluorescence in both solutions and solid states.

We report the switchable optical waveguide microfibers based on fluorescent supramolecular polymer for the first time. The pillar[5]arene-based supramolecular polymeric microfibers were prepared easily from the viscous solution of bispillar[5]arene host (bisP5A) and diphenylanthracene-derived guest (GD). The resulting microfibers  act as an active optical waveguide material with long propagation distance (400 μm) and low optical propagation loss (0.01 dB/μm). When photoresponsive dithienylethene-derived guest (GDTE) was added, the resulting ternary microfibers show switchable optical waveguide by the noninvasive control of UV/vis light with negligible fatigue over four cycles. This convenient preparation method is also applied for the quadruple-hydrogen-bonded fluorescent supramolecular polymeric microfibers which imply good light propagation property with an optical loss coefficient of 0.02 dB/μm.

We report a turn-on fluorescent probe for H2S through a cascade reaction using a new trap group 4-(bromomethyl)benzoate based on excited-state intramolecular proton transfer (ESIPT) sensing mechanism.

The bidirectional singlet–singlet and triplet–triplet energy transfer processes were observed for the first time within a noncovalent hydrogen-bonded module. For this purpose, 2-ureido-4[1H]-pyrimidinone quadruple hydrogen-bonds (UPy) functionalized BF2-chelated dipyrromethene (BODIPY-UPy) and iodinated BODIPY (I-BODIPY-UPy) were synthesized. These molecules formed energy donor–acceptor assembly through quadruple self-complementary hydrogen bonds, which demonstrated interesting photophysical properties. Spectroscopic studies in toluene solution revealed that selective excitation of BODIPY-UPy in the assembly resulted in efficient intra-assembly singlet energy transfer from excited BODIPY-UPy to I-BODIPY-UPy. This was followed by intersystem crossing of I-BODIPY-UPy from S1to T1and the backward triplet energy transfer from the I-BODIPY to BODIPY part. Time-resolved transient absorption spectroscopy confirmed that the triplet excited-state energy was distributed on both chromophores in the assembly. Density functional theory (DFT) calculations further validated the feasibility of energy transfer as well as two degenerate triplet states in the assembly. The present studies revealed that the bidirectional singlet–singlet and triplet–triplet energy transfer processes could be manipulated through the noncovalent quadruple hydrogen bonds. Studies on such a process in supramolecular assembly are of considerable importance in the elucidation of their possible function in natural photosystems and inspire applications in various fields such as luminescent materials, optoelectronic devices, photocatalysis, and photodynamic therapy.

A new monofunctionalized pillar[5]arene bearing imidazolium moiety that formed stable [1]pseudorotaxane even at high concentration (100mmol/L) was reported. [1]Rotaxane was obtained efficiently through thiol-ene reaction from [1]pseudorotaxane which further confirmed the formation of [1]pseudorotaxane.

We reported a BODIPY analogue with interesting structural and photophysical properties.

Cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) are interconnected and play essential roles for regulating the redox balance of biological processes. However, finding a simple and effective method for the simultaneous determination for these three biothiols in biological systems is always a challenge. In this work, we report a method for the simultaneous quantitative determination of three biothiols in a mixture using a monochlorinated boron dipyrromethene (BODIPY)-based fluorometric sensor. At a specified period of time, after reacting with excess sensor, Hcy and GSH form predominantly sulfur-substituted BODIPY, while Cys generates sulfur-amino-diBODIPY due to a fast substitution–rearrangement–substitution reaction. A significant difference in polarities of these respective major products simplifies their separation by TLC, thus leading to the simultaneous determination of Cys, Hcy, and GSH readily. The sensor was successfully applied for the simultaneous quantitative detection of three biothiols in human serum, and the results were in good agreement with those obtained via high performance liquid chromatography (HPLC).

Stable gold nanochains with branched features were fabricated at room temperature with the assistance of polyvinylpyrrolidone (PVP). An attachment and fusion process was believed to responsible for the formation of the chain-like structure. During the process, PVP acted both as a structure-directing agent and as a stabilizer to inhibit continuous size increase. UV−vis−NIR study revealed that the unique structure shifted the longitudinal surface plasma resonant band (LSPR) to as far as 1457 nm, which may endow the product with new applications. The surface-enhanced Raman scattering activity was investigated with p-aminothiophenol as probe molecule. The enhancement factor (EF) of the products deposited as film on the Si substrate was estimated to be (1.03 ± 0.74) × l0 6for the a1-type band, while it was (1.32 ± 0.15) × l0 7for b2-type band. The enhancement of a1modes was attributed to the electromagnetic mechanism, whereas the additional EF for the b2mode is presumed to contribute from the chemical effect.