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Infection and dissemination of influenza viruses (IVs) causes serious health concerns worldwide. However, effective tools for the accurate detection and blocking of IVs remain elusive. Here, we develop a new sialyllactosyl probe with self-assembled core-shell structure for the ratiometric detection and blocking of IVs. N,N′-diaryl-dihydrodibenzo[a,c]phenazines were used to form the core structure by hydrophobic assembly in an aqueous solution with an aggregation-enhanced blue fluorescence mission. Subsequently, dicyanomethylene-4H-pyran-based sialyllactosides were used for self-assembly with the core structure, producing the sialyllactosyl probe that emits a red fluorescence due to Forster resonance energy transfer. The probe developed has been proven to be available for (1) the fluorescence ratiometric detection of IVs through selective interaction with the sialyllactosyl-binding proteins on the virus surface, and (2) effectively blocking the invasion of human-infecting IVs towards host cells as accentuated by the sialyllactosides on the surface of the probes.

Summary Membrane receptors, among other membrane proteins that universally exist on the cell surface, are a class of important macromolecules responsible for cell-signaling processes. They are activated or inhibited through selective binding with endogenous ligand molecules. These binding activities are implicated in physiologic as well as pathologic events if errors in signaling interactions occur. The thorough understanding of receptor-ligand recognition is of paramount importance for fundamental biological studies and, in particular, could improve the precision of disease diagnosis and therapy. However, current techniques capable of tracking the dynamic actions of membrane receptors are elusive. This review highlights our recent progress in the development of fluorescent probes and supramolecular materials for receptor-targeting biosensing and bioimaging. Strategies in probe construction and the practical biomedical applications that have been achieved are discussed. Perspectives and challenges with respect to this interdisciplinary field are offered.

We have developed a new series of glycoprobe-polymer dot ensembles for the fluorogenic, homogeneous detection of lectins. Electrostatic self-assembly between positively charged rhodamine-based glycosides and negatively charged poly(3-hexylthiophene-2,5-diyl)/poly(styrene-co-maleic anhydride) polymer dots produces the ensembles with a quenched fluorescence. Fluorescence spectroscopy showed that the ensembles exhibited a concentration-dependent fluorescence enhancement with selective lectins over a range of unselective lectins and proteins. This research provides insight into the development of simple fluorogenic probes for homogeneous lectin analyses based on the supramolecular assembly between polymeric nanoparticles and fluorescent glycoprobes.

As a common environmental pollutant, the sulfide anion (S2−) is toxic to the human body. We report here the simple preparation of a selective fluorogenic glycoprobe–metal complex for the rapid analysis of S2− in full aqueous solution and real water samples. The probe was synthesized by “clicking” a dipropargyl naphthalimide dye with a water-soluble azido β- d -galactoside. Fluorescence spectroscopic analyses showed that the probe had an on–off response to Cu2+, forming a fluorogenic probe–Cu2+ complex. The subsequent addition of S2− selectively recovered the fluorescence of the complex over other anions tested, probably because of the high-affinity association between Cu2+ and S2−. The complex showed a good linear range and a nanomolar limit of detection with S2− in full aqueous solution, and has also proven to be suitable for accurate recovery of spiked S2− in real water samples.

The effective imaging of amyloid β (Aβ) in vivo is important for the diagnosis of Aβ-related diseases such as the Alzheimer's disease (AD). Here we report a donor-acceptor-donor (D-A-D) type fluorogenic probe for the rapid imaging of amyloid β (Aβ) senile plaques in a transgenic mouse brain. The probe that features a dicyanomethylene-4H-pyran (DCM) core shows a concentration-dependent fluorescence enhancement with Aβ42 and Aβ40, which are the main components of Aβ fibrils formed in the brain of AD patients. The D-A-D probe can also be used to rapidly sense Aβ peptide monomer, oligomer and fibril in an aqueous solution and image the morphologically diverse Aβ species by confocal microscopy. In particular, we demonstrate that the probe can be used to rapidly stain Aβ senile plaques in the brain of transgenic mice by intravenous injection.

A series of galactosyl naphthalimide-piperazine derivatives have been synthesized as intracellular pH and lysosome-targeting imaging probes for live human hepatoma cells. The probes show good sensitivity in both aqueous buffer and intracellular environments. Incorporation of the galactose moiety with the pH probes facilitates their specific endocytosis and, thus targeted trafficking to lysosome, by the asialoglycoprotein receptor of human hepatoma cells. The acidic intracellular pH of live human hepatoma cells gives rise to a fluorescence “turn-on” signal of the probes probably via a modulation of the photo-induced electron transfer (PET) mechanism. Additionally, galactosylation of the probes enhances their selective accumulation in lysosome and decreases the cytotoxicity.

A new series of arene chlorido ruthenium and pentamethylcyclopentadienyl chlorido rhodium complexes containing o -sulfonamide azobenzene ligands with an exocyclic N N bond coordination pattern have been synthesized. These complexes undergo readily E → Z photoisomerization followed by thermal Z → E isomerization (upon resting in the dark). The ruthenium complexes showed low-micromole-ranged cytotoxicity towards a panel of cancer cells. Western blotting and flow cytometric analyses suggest that 1) they are potent apoptotic inducers for cancer cells, probably through a caspase-3 dependent apoptotic pathway, and that 2) they have a much stronger ability to induce HeLa cancer cell apoptosis than cisplatin, a commercial anticancer drug.

Lipid droplets (LDs) are cellular organelles that are essential for maintaining lipid and energy homeostasis. Once regarded as merely inert fat particles, they are now recognized as highly dynamic, mobile organelles required for preventing lipotoxicity and for interacting and cooperating with various organelles. Despite the progress made in understanding the role of LDs, a number of fundamental questions remain unanswered. Effective imaging agents for observing the morphology and dynamic physiological processes of LDs in cells could help address this knowledge gap. Such probes are expected to aid in our understanding of LDs and facilitate the development of new and effective therapeutics. In this review, we have provided a brief introduction to the formation and physiological functions of LDs in an attempt to highlight the importance of these underappreciated organelles. Recent examples of LD-based fluorescent probes are discussed, including the fluorescence phenomenon used in their design. To date, both intramolecular charge transfer (ICT) and aggregation-induced emission (AIE) fluorescence mechanisms have been exploited to create LD probes. However, alternative strategies can be envisioned. We hope the readers will be enlightened as to the importance of these key organelles, will be poised to exploit existing probes to explore various biological applications, and be inspired to create new LD fluorescent sensors that will further our understanding of LDs and their associated physiology.

Detection of live cells has been difficult with conventional biochemical techniques that require the lysis of cells to release a biomarker. This study describes the simple construction of a galactosyl anthraquinone dye for the label-free impedance detection of live cancer cells. A click dipolar reaction of an alkynyl anthraquinone with azido galactoside yields the anthraquinone probe which can be subsequently employed to bind to a graphene-coated screen printed electrode by self-assembly. By taking advantage of selective sugar-receptor recognitions, live cancer cells without being labeled, can be captured by the electrode, producing a sensitive impedance signal. Knockdown of the receptor leads to a sharp decrease of the impedance signal, suggesting the suitability of the electrode system for the direct live cell capture based on ligand-receptor recognitions.

Although being widely used in organic synthesis, thiophenol (Tp) is toxic to the human body. We report here the preparation of a ratiometric fluorescence probe for the selective, transient determination of Tp in full aqueous solution. The probe was synthesized by a click reaction coupling between an alkynyl naphthalimide-dansyl dyad and an azido galactoside which increases the water solubility. Fluorescence spectroscopic analyses showed that the probe had a specific ratiometric response to Tp transiently in a full aqueous solution, over a range of other species. The probe has also proven suitable for the quantification of Tp in environmental water samples, and possesses superior properties to previous Tp fluorescence probes in terms of water solubility and sensitivity.

This study describes an interesting observation that the mixture of anomeric galactolipids has synergistic effects on the growth inhibition of human multiple myeloma (MM) cells. We determine that the equivalent mixture of a pair of α- and β-galactolipids with a 14-carbon lipid chain can cause stronger poly ADP-ribose polymerase cleavage and DNA damage, producing more late apoptotic MM cells, than either anomer alone.

Structurally modified N-fluorobenzenesulfonimides (NFSIs) have been used to study the enantioselective fluorination of oxindoles in the presence of a bis-cinchona alkaloid, (DHQD)2PHAL, as the catalyst. We observe that the NFSI analogues bearing two tert-butyl groups at the para-position of the symmetric phenyl rings led to an enhanced enantioselectivity in most cases (up to 96% ee) compared with the unmodified NFSIs (less than 69% ee).

Glycoligands, which feature a glycoside as the central template incorporating Lewis bases as metal chelation sites and various fluorophores as the chemical reporter, represent a range of interesting scaffolds for development of chemosensors. Here, new types of triazolyl bidentate glycoligands (TBGs) based on the grafting of 3-azidocoumarin to the C2,3- or C4,6-positions of three epimeric pyranoglycosides including a glucoside, a galactoside, and a mannoside were efficiently synthesized via a fluorogenic dual click reaction assisted by microwave irradiation. The desired TBGs were afforded in high conversion rates (>90%) and reasonable yields (∼70%). Moreover, a preliminary optical study of two hydroxyl-free glucoside-based TBGs indicates that these compounds are strongly fluorescent in pure water, implying their potential for ion detections in aqueous media.

The stereoselectivity of the reaction of (Rs)-trifluoromethyl α,β-unsaturated N-tert-butanesulfinyl ketimines with TMSCN was studied. The diastereomers of α-trifluoromethyl unsaturated cyano amines were obtained, respectively, in good yields with excellent diastereoselectivities in terms of the different solvents used. In c-hexane, the (S, Rs)-isomer was obtained with up to 17:1 dr, whereas the (R, Rs)-isomer was generated as the main product with up to 145:1 dr in DMF at −60 °C.

The corrosion inhibitive efficiency of diverse 1,2,3-triazolyl benzyl glucoside-, galactoside- and mannoside-serine/threonine conjugates readily synthesized via Cu I -catalyzed azide–alkyne cycloaddition reaction (Cue-AAC) for mild steel in HCl was examined via electrochemical impedance spectroscopy. The results indicate that these compounds are potent corrosion inhibitors even in highly concentrated HCl solutions. The potential mechanism of three inhibitors was characterized in detail via polarization and isotherm calculations. This study implies that benzyl glycoside-amino acid hybrids effectively constructed via the Cue-AAC between the highly biocompatible sugars and amino acids may represent a new class of promising and potentially green corrosion inhibitors.

Triazolyl glycolipid derivatives constructed via CuI-catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction (Cue-AAC) represent a new range of carbohydrate-based scaffolds for use in many fields of the chemical research. Here the surface adsorptive ability of series of our previously prepared C1- or C6-triazole linked gluco- and galactolipid derivatives for mild steel in 1 M HCl was studied via electrochemical impedance spectroscopy (EIS). Results indicated that these monosaccharide–fatty acid conjugates are weak inhibitors against HCl corrosion for mild steel. Moreover, some newly synthesized triazolyl disaccharide (maltose)–fatty alcohol conjugates failed to display enhanced activity, meaning that the structural enlargement of the sugar moiety does not favor the iron surface adsorption. However, a bis-triazolyl glycolipid derivative, which was realized by introducing a benzenesulfonamide group via Cue-AAC to the C6-position of a C1-triazolyl glucolipid analog, eventually showed significantly improved adsorptive potency compared to that of its former counterparts. The corrosion inhibitive modality of this compound for mild steel in HCl was subsequently studied via potentiodynamic polarization and thermodynamic calculations.

Triazolyl bis-amino acid derivatives readily synthesized via click chemistry were identified as novel potent corrosion inhibitors for mild steel in HCl. The inhibitive characteristic of compound 4 was studied in detail via gravimetric measurement, electrochemical impedance spectroscopy, potentiodynamic polarization and scanning electron microscopy. In addition, a quantum chemical study suggests that the triazole ring involved in these inhibitors is structurally essential for the protection of metal surface.

With an aim of developing novel protein tyrosine phosphatase (PTP) 1B inhibitors based on sugar scaffolds, a focused library of benzyl 6-triazolo(hydroxy)benzoic glucosides was efficiently constructed via the modular and selective Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddtion (click chemistry). These glycoconjugates bearing alkyl chain length-varied bridges between the sugar and (hydroxy)-benzoic moieties were identified as new PTP1B inhibitors with selectivity over T-Cell PTP (TCPTP), SH2-Containing PTP-1 (SHP-1), SHP-2 and Leukocyte Antigen-Related Tyrosine Phosphatase (LAR). Molecular docking study sequentially elaborated the plausible binding modes of the structurally diverse sugar-based inhibitors with PTP1B.

Fluorogenic click chemistry has recently emerged as an ingenious and powerful tool toward numerous biochemical purposes. We describe herein the use of dual click chemistry toward the fluorescence restoration of a fluorogenic coumarin on epimeric dipropargyl sugar scaffolds and their practical utility in selective metal ion detection. The dual click reactions were smoothly proceeded under microwave irradiation between silylated 3,4-di-O-propynyl gluco- or galactoside and 3-azidocoumarin, forming fluorescently reactivated bis-triazolocoumarins on sugar templates. Subsequent desilylation resulted in the OH-glycosides with desired water solubility. The following photochemical study disclosed that their fluorescence could be uniquely quenched by silver(I) in aqueous media with very minor responses to the addition of other metal ions. This research would presumably prompt the efficient creation of water soluble and potentially low toxic chemosensors via the fluorogenic dual click chemistry in using the universally existent sugars as the central scaffold.

A novel triazole-linked acetyl-β- N -glucosyl anthraquinone 1 was conveniently synthesized through one-step click chemistry. The functionalized glycoconjugate ( 1 ) exhibited a remarkable blue shift absorption and quenching fluorescence in the presence of trace amounts of Cu 2+ , presumably attributable to intramolecular charge transfer (ICT), which also displayed high selectivity over a series of other metal cations tested in acetonitrile. The result yielded by fluorescence spectroscopy titration suggested a 2:1 ligand-to-metal complex which was further demonstrated by NMR spectroscopy titration. Moreover, the addition of Cu 2+ to 1 also significantly altered its electrochemical behavior which was reflected via differential pulse voltammetry (DPV) measurements. Such optically and electrochemically detectable metal-mediated sugar derivatives could be further used as biosensors for the recognition of multivalent carbohydrate-protein interactions.

There has been considerable interest in the development of protein tyrosine phosphatase (PTP) inhibitors since many of the PTP members are tightly associated with major human diseases including autoimmune disorders, diabetes and cancer. We report here a unique and rapid approach toward the development of novel PTP inhibitor entities based on triazolyl pseudo-glycopeptides. By employing microwave-accelerated Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC or ‘click reaction’), a series of triazole-linked serinyl, threoninyl, phenylalaninyl and tyrosinyl 1-O-gluco- or galactosides have been efficiently synthesized in high yields within only ∼30 min. Successive biological assay identified these glycopeptidotriazoles as favorable PTP1B and CDC25B inhibitors with selectivity over TCPTP, LAR, SHP-1 and SHP-2. Both the structural diversity of the amino acid (Ser, Thr, Phe and Tyr) introduced and the epimeric identity (Glc or Gal) on monosaccharide scaffold were determined to impact the corresponding inhibitory activity and selectivity. In addition, the benzylated sugar scaffold was demonstrated to act as a crucial role for enhancing the binding affinity of the inhibitors with the targeted PTP. Docking simulation was eventually conducted to propose plausible binding modes of this compound series with PTP1B and CDC25B. Our approach readily realized from naturally abundant raw materials (sugar and amino acid) and via facile, regioselective and expeditious synthetic method (microwave-assisted click reaction) might provide new insights toward the ‘click’ fabrication of structurally diverse PTP inhibitors.

Bidentate 1-O-methyl-α- d -pyranoglucosides bearing two triazolyl α-ketoester groups on the 2,6- or 3,4-positions of sugar scaffold were efficiently synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click reaction) in good yields. These newly featured sugar derivatives displayed favorable inhibitory activity on protein tyrosine phosphatase 1B (PTP1B) and unexpected selective fluorescence quenching in the presence of Ni2+.

A series of triazole-linked ester-type glycolipids were efficiently prepared via a two-step sequence involving microwave accelerated ‘click’ chemistry and debenzylation. All carbon chain length varied O-alkynyl fatty esters used to couple with 1-azido-tetra-O-benzyl-β- d -glucoside showed excellent tolerance to the microwave-assisted 1,3-dipolar cycloaddition (click reaction), forming the unique cycloadducts in almost quantitative yields of 92.9–99.0% within a quarter. The desired glycolipids were then readily afforded via the successive hydrogenolysis promoted by PdCl2/H2. Their adsorption competence on gold electrode were evaluated through EIS (electrochemical impedance spectroscopy) measurement and the resulting structure–activity relationship (SAR) was discussed. In addition, the cytotoxicity of this triazolyl glycolipid class on HeLa (cervix cancer) cell line was identified by MTT assay.

The aim of this work was to construct one small interfering RNA (siRNA) eukaryotic expression vector targeting rat nuclear factor (NF)κB p65 and identify its inhibition effect on cell proliferation according to its down-regulation of NF-κB pathway.The p65siRNA expression vector "pGenesil-1.2-p65siRNA" and negative control plasmid "HK" were transfected into the cultured rat cells. After transfection, cells were divided into 4 treatment groups: 1) control cells cultured in complete. Dulbecco modified Eagle medium; 2) lipopolysaccharide (LPS) (1 μg/mL); (3) LPS (1 μg/mL) + HK-transfected; 4) LPS (1 μg/mL) + p65siRNA (pGenesil-1.2-p65siRNA). Thereafter, the protein levels of NF-κB p65 in the cells were detected by Western blotting at 72 hours after LPS stimulation. Furthermore, to observe cell proliferation, the proliferative rate of the cell growth was evaluated by the methylthiazolyl tetrazolium assay (at 24, 48, and 72 hours). The cell cycle distribution at 72 hours was detected by flow cytometry.p65siRNA effectively down-regulated the protein level of p65 (P.05). Meanwhile, the proliferation of cells transfected with p65siRNA expression vector was significantly inhibited (P.05), the ratio of cells at G(0)/G(1) stage markedly increased, and the proportion of cells at S stage was significantly decreased among transfected compared with control cells (P.05).p65siRNA effectively suppressed NF-κB, expression, inhibiting rat cell proliferation induced by NF-κB signal pathway activation.

β- C -Glucosyl and β- C -galactosyl-1,4-dimethoxynaphthalenes have been synthesized using a F 3 CCO 2 Ag/SnCl 4 promoted Friedel–Crafts electrophilic substitution reaction. Both glycosyl acetates and methyl glycosides can be used as glycosyl donors. Further oxidation afforded the corresponding β- C -glycosyl-1,4-naphthoquinones. The in vitro cytotoxic activity of these compounds was evaluated against the A375 cell line.

The anomeric mixture of a series of O-galactolipid derivatives is revealed to be more toxic against several cancer cell lines than their either single component with the pure α- or β-configuration. This interesting phenomenon has been confirmed on pairs of synthesized O-galactosyl anomers bearing length-varied alkyl chains at the lipid end. Furthermore, the most potent mixture was determined inoffensive to a normal cell line tested.