2,6-Bis-arylated phenols are rarely reported and are synthetically challenging. Directed C–H functionalization reactions, using a directing group (DG), might provide a convenient solution to their synthesis. However, this strategy usually results in partial cleavage of the directing group, preventing further/second C–H activation cascades. Herein we report a general strategy that allows for the precise control of the oxidation pathways so that directing groups can be either preserved or cleaved. We found that N-phenoxyacetamides could undergo ortho-arylation reactions with or without an external oxidant, yielding products with different oxidation states, notably the rare bis-arylated phenols. Notably, a unique rhodacycle intermediate was isolated, characterized by X-ray crystallography, and confirmed to be an active catalyst. Switching between internal and external oxidation could be a general strategy in diverse directed C–H functionalization reactions to realize bis-functionalized products.

•Three-dimensional polypyrrole-derived carbon nanotube frameworks are prepared.•They display outstanding absorption capacity (609 mg g−1) towards methylene blue.•They possess high specific capacitance (167 F g−1) and good rate capability (64%).•They have excellent cycling performance with no capacitance loss over 1000 cycles.Three-dimensional carbon nanotube frameworks have been prepared via pyrolysis of polypyrrole nanotube aerogels that are synthesized by the simultaneous self-degraded template synthesis and hydrogel assembly followed by freeze-drying. The microstructure and composition of the materials are investigated by thermal gravimetric analysis, Raman spectrum, X-ray photoelectron spectroscopy, transmission electron microscopy, and specific surface analyzer. The results confirm the formation of three-dimensional carbon nanotube frameworks with low density, high mechanical properties, and high specific surface area. Compared with PPy aerogel precursor, the as-prepared three-dimensional carbon nanotube frameworks exhibit outstanding adsorption capacity towards organic dyes. Moreover, electrochemical tests show that the products possess high specific capacitance, good rate capability and excellent cycling performance with no capacitance loss over 1000 cycles. These characteristics collectively indicate the potential of three-dimensional polypyrrole-derived carbon nanotube framework as a promising macroscopic device for the applications in environmental and energy storages.Download high-res image (95KB)Download full-size image

The coordination bond between gold and sulfur (Au–S) has been widely studied and utilized in many fields. However, detailed investigations on the basic nature of this bond are still lacking. A gold-specific binding protein, GolB, was recently identified, providing a unique opportunity for the study of the Au–S bond at the molecular level. We probed the mechanical strength of the gold–sulfur bond in GolB using single-molecule force spectroscopy. We measured the rupture force of the Au–S bond to be 165 pN, much lower than Au–S bonds measured on different gold surfaces (∼1000 pN). We further solved the structures of apo-GolB and Au(I)–GolB complex using X-ray crystallography. These structures showed that the average Au–S bond length in GolB is much longer than the reported average value of Au–S bonds. Our results highlight the dramatic influence of the unique biological environment on the stability and strength of metal coordination bonds in proteins.

In the heart, glycosylation is involved in a variety of physiological and pathological processes. Cardiac glycosylation is dynamically regulated, which remains challenging to monitor in vivo. Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. We further applied this methodology to investigate the sialylation in hypertrophic hearts. The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses.

A lead-specific binding protein, PbrR, and promoter pbr from the lead resistance operon, pbr, of Cupriavidus metallidurans CH34 was incorporated into E. coli in conjunction with an engineered downstream RFP (red fluorescence protein), which allowed for highly sensitive and selective whole-cell detection of lead ions. The subsequent display of PbrR on the E. coli cell surface permitted selective adsorption of lead ions from solution containing various heavy metal ions. The surface-engineered E. coli bacteria effectively protected Arabidopsis thaliana seed germination from the toxicity of lead ions at high concentrations. Engineering the E. coli bacteria harboring these lead-specific elements from the pbr operon may potentially be a valuable general strategy for biodetection and bioremediation of toxic heavy metal ions in the environment.

A naphthalimide-azide based colorimetric and ratiometric fluorescent probe, NAP-1, has been developed for the selective and sensitive detection of hydrogen sulphide. Advantages of the probe NAP-1 include a low detection limit (110 nM), good selectivity, high sensitivity and excellent photostability. A linear relationship between the emission intensity ratios and sulphide concentrations was observed in PBS buffer and bovine serum, respectively. Our probe facilitates ratiometric determination and imaging of endogenous H2S in living cells. Furthermore, this probe was successfully applied to the measurement of endogenous sulphide in human plasma and mouse hippocampus. A significant reduction in sulphide levels and CBS mRNA expression was observed in the hippocampus of mouse models of lipopolysaccharide-induced neuroinflammation-related diseases, suggesting that decreased levels of endogenous H2S might be involved in the pathogenesis of neuroinflammation-related neurodegenerative diseases.

We report the design and synthesis of a series of new cyclometalated iridium hydrides derived from the C–H bond activation of aromatic nitrones and the biological evaluation of these iridium hydrides as antitumor agents. The nitrone ligands are based on the structure of a popular antioxidant, α-phenyl-N-tert-butylnitrone (PBN). Compared to cisplatin, the iridium hydrides exhibit excellent antitumor activity on HepG2 cells. The metal-coordinated compound with the most potent anticancer activity, 2f, was selected for further analysis because of its ability to induce apoptosis and interact with DNA. During in vitro studies and in vivo efficacy analysis with tumor xenograft models in Institute of Cancer Research (ICR) mice, complex 2f exhibited antitumor activity that was markedly superior to that of cisplatin. Our results suggest, for the first time, that metal hydrides could be a new type of metal-based antitumor agent.

We describe the design, synthesis and application of a sensitive, selective, and fast fluorescent probe for H2S detection. A linear relationship between emission intensity and sulfide concentration was observed in biological bovine plasma systems. With this probe, we were able to estimate the sulfide concentration in mouse blood plasma and brain tissues.

A gold-specific sensory protein GolS from Samonella gol regulon was incorporated into E. coli, which in conjunction with an engineered downstream red fluorescence protein allowed the highly sensitive and selective whole-cell detection of gold(III) ions by naked eyes. The putative gold-chaperone, GolB, in the gol regulon was next verified to be specific to gold(I) ions over other metal ions including copper(I). The subsequent display of GolB on E. coli cell surface permitted selective enrichment of gold ions from media containing various thiophilic metal ions. The cell surface-enriched gold(I) was further shown to be easily recovered and the gold-deprived bacteria were capable for re-usage. E. coli bacteria harboring these gold-specific elements from the gol regulon could be a valuable tool for visual detection and facile recycling of gold ions from environmental resources.

We report a preparation method for the synthesis of monodisperse magnetic polymer/silica hybrid microspheres using polymer microspheres incorporated with magnetic nanoparticles as a novel template. Monodisperse, hierarchically mesoporous, silica microspheres embedded with magnetic nanoparticles were successfully fabricated after the calcination of the hybrid microspheres. The magnetic nanoparticles were encapsulated in silica and distributed over the whole area of the porous microspheres without leakage. The resulting inorganic materials possess highly useful properties such as high magnetic nanoparticle loading, high surface area, and large pore volumes. The hierarchically mesoporous magnetic silica microspheres resulted in a high bovine serum albumin (BSA) protein adsorption capacity (260 mg/g) and a fast adsorption rate (reaching equilibrium with 8 h).Keywords: hierarchical pores; magnetic nanoparticles; mesoporous silica; microspheres; protein adsorption;

A series of novel gemifloxacin (GMFX) derivatives containing a substituted benzyloxime moiety with remarkable improvement in lipophilicity were synthesized. The target compounds evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that most of the target compounds have considerable potency against all of the tested Gram-positive strains including MRSA and MRSE (MIC: <0.008–8 μg/mL), although they are generally less active than the references against the Gram-negative strains. In particular, compound 11l (MIC: <0.008–4 μg/mL) was found to be 8–2048 and 2–128 times more potent than levofloxacin (LVFX) and GMFX against the Gram-positive strains, respectively. Moreover, against MRSA clinical isolates, 11l (MIC90: 1 μg/mL) is 8-fold more active than GMFX, and 2-fold more active than GMFX and moxifloxacin against MRSE clinical isolates (MIC90: 4 μg/mL).Graphical abstractA series of novel gemifloxacin derivatives with remarkable improvement in lipophilicity were synthesized and compound 11l is found to be 8–2048 and 2–128 times more potent than levofloxacin and gemifloxacin against the Gram-positive strains.Highlights► Most of the compounds showed potent activity against Gram-positive strains. ► 11l was 2–2048 times more potent than levofloxacin and GMFX. ► 11l was more active than GMFX and moxifloxacin against MRSE clinical isolates. ► Structure–activity relationships of these compounds have been discussed.

The host–guest interaction between symmetrical α,α′,δ,δ′-tetramethyl-cucurbit[6]uril (TMeQ[6]) and methylviologen (N,N′-dimethyl-4,4′-bipyridinium, MV) dication was investigated both in aqueous solution and in the solid state using NMR spectroscopic methods and single-crystal X-ray diffraction analysis. In the aqueous solution, TMeQ[6] forms a 1:1 inclusion complex with methylviologen MV2+, and the chemical exchange of the MV2+ guest in and out of the cavity of the TMeQ[6] host was fast on the NMR time scale. In the solid state, however, the MV2+ guest was partially encapsulated into the TMeQ[6] host. We found that the chemical environment of the TMeQ[6] host underwent a severe change during the encapsulation process. Interestingly, electrochemical studies revealed that, unlike other cucurbiturils, TMeQ[6] has the same level of binding affinity to the charged forms (MV2+ and MV+˙) and the fully reduced form (MV0). These studies contribute to the fundamental understanding of the interdependence of electron-transfer processes and molecular recognition.

A catalytic protocol was developed to synthesize N-aryl-d-glucosamines from the corresponding aryl halides. Cross-coupling of 1,3,4,6-tetra-O-benzyl-β-d-glucosamine with aryl iodides or bromides was catalyzed with copper. Subsequent deprotection of the benzyl group gave the arylation product N-aryl-d-glucosamines.

Chiral squaramides are highly enantioselective catalysts for Friedel–Crafts reaction of indoles with N-tosyl imines, affording 3-indolyl methanamine products in 85–96% yields and 84–96% ees.

Chelation-assisted activation of C−X bonds (X = Cl, Br, and I) took place in the reaction of [Rh(PPh3)2(acetone)2]+ and 2-(2-halophenyl)pyridine or 10-halobenzo[h]quinoline. A series of 16-electron five-coordinate cationic rhodium(III) monohalide complexes was synthesized at room temperature. Neutral octahedral rhodium(III) dihalide complexes were obtained when the corresponding cationic monohalide complexes were further heated in acetone. Rhodium and iridium diiodides with these cyclometalation motifs could be alternatively synthesized from the reaction of the corresponding cyclometalated hydride complexes and I2. X-ray crystal structures of representative monohalide and dihalide complexes are reported. Octahedral rhodium(III) dihalide complexes are active catalysts for the dimerization of terminal alkynes, while 16-electron cationic rhodium(III) monohalides are inactive.

A series of peptide and Schiff bases (PSB) were synthesized by reacting salicylic acid, primary diamines with salicylaldehyde or its derivatives, and 40 of which were newly reported. The inhibitory activities against Escherichia coli β-ketoacyl-acyl carrier protein synthase III (ecKAS III) were investigated in vitro and molecular docking simulation also surveyed. Top 10 PSB compounds which posses both good inhibitory activity and well binding affinities were picked out, and their antibacterial activities against Gram-negative and Gram-positive bacterial strains were tested, expecting to exploit potent antibacterial agent with broad-spectrum antibiotics activity. The results demonstrate compound N-(3-(5-bromo-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (2d) can be as a potential antibiotics agent, displaying minimal inhibitory concentration values in the range of 0.39–3.13 μg/mL against various bacteria.The inhibitory activities of 44 PSB against Escherichia coli β-ketoacyl-acyl carrier protein synthase III (ecKAS III) were investigated in vitro and molecular docking simulation also surveyed. The results demonstrate compound N-(3-(5-bromo-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (2d), bonding two active site of ecKAS III and fit into the mouth of the substrate tunnel, can be as a potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.39–3.13 μg/mL against various bacteria.

Neutral and cationic Pd(II) and Ni(II) OCO-type pincer complexes have been synthesized from the metalation of 1,3-dinitrones via C−H or C−Br bond activation using Pd(0), Pd(II), and Ni(0) starting materials. In each complex, the two six-membered metallacycles are non-coplanar and atropisomerization proceeds with a low barrier. Palladium dinitrone complexes have been shown as active catalysts for Heck couplings and the related Ni complex for Kumada reactions with turnover numbers up to 950 000.

A rare η3 binding mode of aryloxides was obtained in the reaction of BINOL and [Cp*IrCl2]2. Interconversions between and η1 and η3 modes of aryloxides were observed by VT NMR spectroscopy, and the activation barrier was measured. The preference of this binding mode as a function of phenols was discussed.

A novel series of Indy-N-heterocyclic carbene ligands (Indy = indazolin-s-ylidene) have been developed and investigated. Via a mild Ag carbene transfer route, these new carbene ligands reacted with rhodium, palladium, and gold salts to yield the corresponding air-stable metal complexes. The product complexes were characterized by NMR spectroscopic methods and X-ray diffraction analysis. The electronic properties of these complexes were modified by the introduction of different substituents at the coordinated NHC ligands. Catalytic properties of the gold complex were evaluated in the hydration of alkynes to give the corresponding ketone products. This new type of gold N-heterocyclic carbene complex showed a high catalytic activity in the hydration of alkyne at room temperature.

We describe the design, synthesis and application of a sensitive, selective, and fast fluorescent probe for H2S detection. A linear relationship between emission intensity and sulfide concentration was observed in biological bovine plasma systems. With this probe, we were able to estimate the sulfide concentration in mouse blood plasma and brain tissues.

A gold-specific sensory protein GolS from Samonella gol regulon was incorporated into E. coli, which in conjunction with an engineered downstream red fluorescence protein allowed the highly sensitive and selective whole-cell detection of gold(III) ions by naked eyes. The putative gold-chaperone, GolB, in the gol regulon was next verified to be specific to gold(I) ions over other metal ions including copper(I). The subsequent display of GolB on E. coli cell surface permitted selective enrichment of gold ions from media containing various thiophilic metal ions. The cell surface-enriched gold(I) was further shown to be easily recovered and the gold-deprived bacteria were capable for re-usage. E. coli bacteria harboring these gold-specific elements from the gol regulon could be a valuable tool for visual detection and facile recycling of gold ions from environmental resources.

2,6-Bis-arylated phenols are rarely reported and are synthetically challenging. Directed C–H functionalization reactions, using a directing group (DG), might provide a convenient solution to their synthesis. However, this strategy usually results in partial cleavage of the directing group, preventing further/second C–H activation cascades. Herein we report a general strategy that allows for the precise control of the oxidation pathways so that directing groups can be either preserved or cleaved. We found that N-phenoxyacetamides could undergo ortho-arylation reactions with or without an external oxidant, yielding products with different oxidation states, notably the rare bis-arylated phenols. Notably, a unique rhodacycle intermediate was isolated, characterized by X-ray crystallography, and confirmed to be an active catalyst. Switching between internal and external oxidation could be a general strategy in diverse directed C–H functionalization reactions to realize bis-functionalized products.

Chiral squaramides are highly enantioselective catalysts for Friedel–Crafts reaction of indoles with N-tosyl imines, affording 3-indolyl methanamine products in 85–96% yields and 84–96% ees.

A naphthalimide-azide based colorimetric and ratiometric fluorescent probe, NAP-1, has been developed for the selective and sensitive detection of hydrogen sulphide. Advantages of the probe NAP-1 include a low detection limit (110 nM), good selectivity, high sensitivity and excellent photostability. A linear relationship between the emission intensity ratios and sulphide concentrations was observed in PBS buffer and bovine serum, respectively. Our probe facilitates ratiometric determination and imaging of endogenous H2S in living cells. Furthermore, this probe was successfully applied to the measurement of endogenous sulphide in human plasma and mouse hippocampus. A significant reduction in sulphide levels and CBS mRNA expression was observed in the hippocampus of mouse models of lipopolysaccharide-induced neuroinflammation-related diseases, suggesting that decreased levels of endogenous H2S might be involved in the pathogenesis of neuroinflammation-related neurodegenerative diseases.