New Fluorophore and Its Applications in Visualizing Polystyrene Nanoplastics in Bean Sprouts and HeLa Cells.

In the domain of environmental science, pollutants of nanoscale plastic dimensions are acknowledged as subjects of intricate significance. Such entities, though minuscule, present formidable challenges to ecological systems and human health. The diminutive dimensions of these contaminants render their detection arduous, thus demanding the inception of avant-garde methodologies. The present manuscript postulates the employment of the tetraphenylethylene functional group with a fused xanthene (TPEF), a distinguished fluorophore, as an exemplary system for the discernment of nanoplastic particulates. The synthesis and characterization of TPEF have been exhaustively elucidated, revealing its paramount fluorescence attributes and inherent affinity for interaction with nanoplastics. When subjected to comparison with TPEF, nanoplastics are observed to manifest a more pronounced fluorescent luminescence than when associated with the conventional Nile Red (NR). Particularly, the TPEF has shown exceptional affinity for polystyrene (PS) nanoplastics. Further, the resilience of nanoplastics within the hypocotyl epidermis of soybeans, as well as their persistence in mung bean sprouts subsequent to rigorous rinsing protocols, has been meticulously examined. Additionally, this investigation furnishes empirical data signifying the existence of nano-dimensional plastic contaminants within HeLa cellular structures. The urgency of addressing the environmental ramifications engendered by these diminutive yet potent plastic constituents is emphatically highlighted in this manuscript. TPEF paves the way for prospective explorations, with the aspiration of devising efficacious mitigation strategies. Such strategies might encompass delineating the trajectories undertaken by nanoplastics within trophic networks or their ingress into human cellular architectures.

An AIE-Active NIR Fluorescent Probe with Good Water Solubility for the Detection of Aß1-42 Aggregates in Alzheimer's Disease.

Alzheimer's disease (AD), an amyloid-related disease, seriously endangers the health of elderly individuals. According to current research, its main pathogenic factor is the amyloid protein, which is a kind of fibrillar aggregate formed by noncovalent self-assembly of proteins. Based on the characteristics of aggregation-induced emission (AIE), a bislactosyl-decorated tetraphenylethylene (TPE) molecule TMNL (TPE + malononitrile + lactose), bearing two malononitrile substituents, was designed and synthesized in this work. The amphiphilic TMNL could self-assemble into fluorescent organic nanoparticles (FONs) with near-infrared (NIR) fluorescence emission in physiological PBS (phosphate buffered saline), achieving excellent fluorescent enhancement (47-fold) upon its combination with Aß1-42 fibrils. TMNL was successfully applied to image Aß1-42 plaques in the brain tissue of AD transgenic mice, and due to the AIE properties of TMNL, no additional rinsing process was necessary. It is believed that the probe reported in this work should be useful for the sensitive detection and accurate localization mapping of Aß1-42 aggregates related to Alzheimer's disease.

In Situ Self-Assembled J-Aggregate Nanofibers of Glycosylated Aza-BODIPY for Synergetic Cell Membrane Disruption and Type†I Photodynamic Therapy.

The in situ self-assembly of exogenous molecules is a powerful strategy for manipulating cellular behavior. However, the direct self-assembly of photochemically inert constituents into supramolecular nano-photosensitizers (PSs) within cancer cells for precise photodynamic therapy (PDT) remains a challenge. Herein, we developed a glycosylated Aza-BODIPY compound (LMBP) capable of self-assembling into J-aggregate nanofibers in situ for cell membrane destruction and type I PDT. LMBP selectively entered human hepatocellular carcinoma HepG2 cells and subsequently self-assembled into intracellular J-aggregate nanovesicles and nanofibers through supramolecular interactions. Detailed studies revealed that these J-aggregate nanostructures generated superoxide radicals (O2 - ⋅) exclusively through photoinduced electron transfer, thus enabling effective PDT. Furthermore, the intracellular nanofibers exhibited an aggregation-induced retention effect, which resulted in selective toxicity to HepG2 cells by disrupting their cellular membranes and synergizing with PDT for powerful tumor suppression efficacy in vivo.

A BODIPY-carbazole hybrid as a fluorescent probe: the design, synthesis, and discrimination of surfactants and the determination of the CMC values.

Surfactants play important roles in chemical industries and have become well-known environmental pollutants owing to their extensive use in different fields. In this work, we reported a fluorescent probe, namely, BDP-Zn2+ for the discrimination of four kinds of surfactants and the determination of CMC values. BDP-Zn2+ was composed of covalently linked BODIPY, carbazole, N,N-bis(2-pyridylmethyl)ethylenediamine (BPEA) and zinc ions to fabricate a novel push-pull molecular structure. Upon the addition of surfactants, the probe exhibited a turn-on fluorescence response and the emission was enhanced on increasing the surfactant concentrations. This indicated that the fluorescence intensity and the ratios of the emission at 607 nm to that at 514 nm as fingerprints could be used to identify the CMC values of the surfactants. Our current work provides an alternative method to efficiently discriminate different surfactants for the further studies of their physical and chemical functions.

Assembly of BODIPY-carbazole dyes with liposomes to fabricate fluorescent nanoparticles for lysosomal bioimaging in living cells.

Two BODIPY-carbazole dye based fluorescent probes BCA and BCAS were designed, synthesized and encapsulated by liposomes to obtain fluorescent nanoparticles BCA-FNP and BCAS-FNP. The fluorescence imaging showed that BCA-FNP was membrane-permeable and capable of localizing lysosomes in living cells.

Highly efficient α-C-sialylation promoted by (p-Tol)2SO/Tf2O with N-acetyl-5-N,4-O-oxazolidione protected thiosialoside as donor.

Based on a preactivation protocol with (p-Tol)2SO/Tf2O, a practical, straightforward, and high-yielding synthesis of α-sialyl C-glycosides was accomplished by coupling N-acetyl-5-N,4-O-oxazolidione protected thiosialoside with various trimethylsilyl enol ethers and allyltrimethylsilanes. High yields and excellent α-selectivities were obtained for the strong π-nucleophiles with large nucleophilicity values (N = 4.4-9.0), irrespective of whether silyl enol ethers, silyl ketene acetals or allyltrimethylsilanes were used for the electrophilic C-sialylation.

A water-soluble fluorescent organic nano-photosensitizer for the ratiometric detection of mitochondrial G-quadruplexes with photodynamic therapy potential.

We report a water-soluble AIEgen (TPAL) that can self-assemble into fluorescent organic nanoparticles for the ratiometric detection of mitochondrial DNA (mtDNA) parallel G-quadruplexes (G4s) with high selectivity, a low detection limit and photodynamic therapy (PDT) potential.

α-Stereoselective 3-Deoxy-d-manno-oct-2-ulosonoic Acid (Kdo) O-Glycosylation with a p-Toluenethioglycoside Donor by the (p-Tol)2SO/Tf2O Preactivation Strategy.

A convenient and efficient approach was developed to synthesize α-Kdo O-glycosides based on the Tf2O/(p-Tol)2SO preactivation strategy using peracetylated Kdo thioglycoside as a donor. Under the optimized reaction conditions, several O-glycoside products, including α-(2 → 1)-, α-(2 → 2)-, α-(2 → 3)-, and α-(2 → 6)-Kdo products, were stereoselectively synthesized in high yields. Remarkably, a series of aromatic α-Kdo O-glycosides were first and successfully constructed in high yields. An SN2-like mechanism was revealed by DFT calculations and experimental results.

Anti-herpes simplex virus efficacies of 2-aminobenzamide derivatives as novel HSP90 inhibitors.

After the widespread use of the acyclic purine nucleoside analogues for therapy of herpes simplex virus (HSV) infection since the 1980s, new antiviral strategies are urgently needed to counter the emergence of drug-resistant clinical isolates. In this report, we define the anti-HSV efficacies of three optimized 2-aminobenzamide derivatives in vitro and in vivo. The synthetic analogues SNX-25a, SNX-2112 and SNX-7081, which selectively bind to the N-terminal ATP pocket of heat shock protein 90 (HSP90), exhibited significant anti-HSV-1 and HSV-2 activities at non-cytotoxic concentrations in Vero cells, with EC(50) values close to that of acyclovir (ACV). The in vivo antiviral potentials were then confirmed using a herpes simplex keratitis (HSK) rabbit model, where eye gels containing 0.1% or 0.025% SNX-25a displayed the highest efficacies against HSV-1 infection, which were better than that obtained with 0.1% ACV. SNX-2112 and SNX-7081 gels were also effective against HSV-1 with different magnitude of activities. Our results for the first time confirmed the anti-HSV efficacies of these 2-aminobenzamide derivatives and suggest that with alternative mechanisms of action these novel HSP90 inhibitors, especially SNX-25a, could be potent as new anti-HSV clinical trial candidates.

Tetrahydroindazolone substituted 2-aminobenzamides as fluorescent probes: switching metal ion selectivity from zinc to cadmium by interchanging the amino and carbamoyl groups on the fluorophore.

Three fluorescent probes CdABA', CdABA and ZnABA', which are structural isomers of ZnABA, have been designed with N,N-bis(2-pyridylmethyl) ethylenediamine (BPEA) as chelator and 2-aminobenzamide as fluorophore. These probes can be divided into two groups: CdABA, CdABA' for Cd(2+) and ZnABA, ZnABA' for Zn(2+). Although there is little difference in their chemical structures, the two groups of probes exhibit totally different fluorescence properties for preference of Zn(2+) or Cd(2+). In the group of Zn(2+) probes, ZnABA/ZnABA' distinguish Zn(2+) from Cd(2+) with F(Zn)(2+)-F(Cd)(2+) = 1.87-2.00. Upon interchanging the BPEA and carbamoyl groups on the aromatic ring of the fluorophore, the structures of ZnABA/ZnABA' are converted into CdABA/CdABA'. Interestingly, the metal ions selectivity of CdABA/CdABA' was switched to discriminate Cd(2+) from Zn(2+) with F(Cd)(2+)-F(Zn)(2+) = 2.27-2.36, indicating that a small structural modification could lead to a remarkable change of the metal ion selectivity. (1)H NMR titration and ESI mass experiments demonstrated that these fluorescent probers exhibited different coordination modes for Zn(2+) and Cd(2+). With CdABA' as an example, generally, upon addition of Cd(2+), the fluorescence response possesses PET pathway to display no obvious shift of maximum λ(em) in the absence or presence of Cd(2+). However, an ICT pathway could be employed after adding Zn(2+) into the CdABA' solution, resulting in a distinct red-shift of maximal λ(em).

Dual functional amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles for the monitoring and inhibition of insulin amyloid fibrillation based on carbohydrate-protein interactions.

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.

Design and assembly of AIE-active fluorescent organic nanoparticles for anti-counterfeiting fluorescent hydrogels and inks.

Two kinds of AIE-active fluorescent organic nanoparticles were designed and constructed as anti-counterfeiting photoresponsive materials. One is fluorescent organic nanoparticles (TPELs) based on a self-assembly strategy, which were self-assembled from novel amphiphilic tetraphenylethylene (TPE) molecules decorated with a lactose moiety and different photoresponsive tags. The other is polymeric fluorescent organic nanoparticles (F-TPEs) derived from the nanoprecipitation strategy, which utilized pluronic copolymer F127 to encapsulate hydrophobic TPEs without lactosyl modifications. Upon UV light irradiation, these AIE-active materials exhibit different photooxidation behaviors in an aqueous solution to give cyan, orange and green fluorescence emissions, and they were successfully used as an anti-counterfeiting fluorescent hydrogel and ink.

Water-soluble AIE-active fluorescent organic nanoparticles for ratiometric detection of SO2 in the mitochondria of living cells.

We report a water-soluble AIEgen (TYDL) to be self-assembled into fluorescent organic nanoparticles (TYDLs) for specific sensing of SO2 in living hepatoma cells. It is demonstrated that the TYDLs were suitable for ratiometrically detecting endogenous and exogenous SO2 in mitochondria with good selectivity, low detection limit (75 nM) and excellent photostability (>30 min). These findings imply the great potential applications of TYDLs for the diagnosis of SO2-related diseases in cell biology.

Synthesis and in vitro anti-HSV-1 activity of a novel Hsp90 inhibitor BJ-B11.

In this study, a novel Hsp90 inhibitor BJ-B11, was synthesized and evaluated for in vitro antiviral activity against several viruses. Possible anti-HSV-1 mechanisms were also investigated. BJ-B11 displayed no antiviral activity against coxsackievirus B(3) (CVB(3)), human respiratory syncytial virus (RSV) and influenza virus (H1N1), but exhibited potent anti-HSV-1 and HSV-2 activity with EC(50) values of 0.42±0.18 µM and 0.60±0.21 µM, respectively. Additionally, the inhibitory effects of BJ-B11 against HSV-1 were likely to be introduced at early stage of infection. Our results indicate that BJ-B11 with alternative mechanisms of action is potent as an anti-HSV clinical trial candidate.

Recognition of bacterial glycosphingolipids by natural killer T cells.

Natural killer T (NKT) cells constitute a highly conserved T lymphocyte subpopulation that has the potential to regulate many types of immune responses through the rapid secretion of cytokines. NKT cells recognize glycolipids presented by CD1d, a class I-like antigen-presenting molecule. They have an invariant T-cell antigen receptor (TCR) alpha-chain, but whether this invariant TCR recognizes microbial antigens is still controversial. Here we show that most mouse and human NKT cells recognize glycosphingolipids from Sphingomonas, Gram-negative bacteria that do not contain lipopolysaccharide. NKT cells are activated in vivo after exposure to these bacterial antigens or bacteria, and mice that lack NKT cells have a marked defect in the clearance of Sphingomonas from the liver. These data suggest that NKT cells are T lymphocytes that provide an innate-type immune response to certain microorganisms through recognition by their antigen receptor, and that they might be useful in providing protection from bacteria that cannot be detected by pattern recognition receptors such as Toll-like receptor 4.

SNX-2112, a novel Hsp90 inhibitor, induces G2/M cell cycle arrest and apoptosis in MCF-7 cells.

SNX-2112 is a heat shock protein 90 (Hsp90) inhibitor with anticancer properties currently in clinical trials. This study investigated the effects of SNX-2112 on inhibition of cell growth, the cell cycle, and apoptosis in MCF-7 human breast cancer cells, in addition to the various molecular mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis suggest that SNX-2112 inhibits cell growth in a time- and dose-dependent manner more potently than 17-(allylamino)-17-demethoxygeldanmycin (17-AAG), a traditional Hsp90 inhibitor, probably as a result of cell-cycle arrest at the G2/M phase and the induction of apoptosis. Downregulation of Bcl-2 and Bcl-xL, upregulation of Bax, cleavage of caspase-9 and poly (ADP-ribose) polymerase (PARP), and degradation of the breast cancer-related Hsp90 client proteins human epidermal growth factor receptor-2 (HER2), Akt, Raf-1, and nuclear factor kappa-B kinase (IKK) were observed in SNX-2112 treated cells by Western blot assay. These findings suggest that the molecular mechanisms of cell-growth inhibition by SNX-2112 involve activation of the mitochondrial apoptotic pathway and the degradation of breast cancer-related proteins.

Assembly of Water-soluble AIE-active Fluorescent Organic Nanoparticles for Ratiometric Detection of Hypochlorite in Living Cells.

Hypochlorous acid (HOCl) plays a crucial role in many physiological processes and is widely used as bleach, deodorant and fungicide. In this work, we designed an amphiphilic hydrazone fluorescent molecule THG-1 containing hydrophilic sugar units and hydrophobic tetraphenylethylene unit for ratiometric detection of HOCl with high sensitivity and excellent selectivity based on HOCl-triggered hydrolyzation reaction and aggregation-induced emission (AIE) effect. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and scanning electron microscope (SEM) tests. Contrast experiments revealed that the numbers of lactose unit and hydrazone linker were essential for assembly of THG-1 and detection of HOCl. In addition, THG-1 was successfully used for imaging of exogenous and endogenous HOCl in living cells.

Water-soluble AIE-active Fluorescent Organic Nanoparticles: Design, Preparation and Application for Specific Detection of Cyanide in Water and Food Samples.

A dilactosyl-dicyanovinyl-functionalized tetraphenylethene (TPELC) was designed, synthesized and used for ratiometric sensing of cyanide. TPELC was comprised of three moieties (tetraphenylethylene, dicyanovinyl group and lactose unit) in one molecule, making TPELC water-soluble and aggregation-induced emission (AIE)-active and selectively reactive to cyanide. Compared with other reported fluorescent probes containing dicyanovinyl group, TPELC is the first AIE luminogen to be assembled as fluorescent organic nanoparticles (FONs) for sensing of cyanide in water without the use of surfactant or the help of organic solvents based on the nucleophilic addition reaction. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and by protonation of cyanide to reduce the nucleophilicity of cyanide. In addition, TPELC was used for detection of the cyanide content of food samples and test strips were developed to simplify the detection procedure.

Assembly of Anionic Conjugated Polymer with 6-O-Modified PNP-ß-Galactoside for Fluorescence Logic-signal-based Multiplex Detections of Enzymes.

Anionic conjugated polymer (PFP-SO 3-) was assembled with a novel enzymatic substrate 6-O-modified PNP-ß-galactoside (1) for sensitive multiplex enzyme detections. The PFP-SO 3-/1/lipase/ß-galactosidase system has two chemical input signals which are Input 1 (lipase) and Input 2 (ß-galactosidase), and output optical signals such as fluorescence emission at 416 nm or 450 nm. Four types of logic gates, including YES, INH, NAND and AND, were successfully constructed and utilized for multiplex detections of lipase and ß-galactosidase in one tube.

A water-soluble AIE-active polyvalent glycocluster: design, synthesis and studies on carbohydrate-lectin interactions for visualization of Siglec distributions in living cell membranes.

In this work, we designed and synthesized an aggregation-induced emission (AIE)-active tetraphenylethene-decorated pseudo-trisialic acid (TPE3S) and validated its high affinity for Siglecs using microscale thermophoresis techniques. TPE3S was a unique binding-on fluorescent trivalent sialocluster which was successfully utilized for the visualization of Siglecs expressed on the surface of mammalian cells.