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As phenanthroline (phen) possesses great coordination ability with various ions, the development of new chiral phen ligands is in great demand in asymmetric catalysis. Herein, we rationally designed and developed an entirely new class of C2-symmetric rigid-featured chiral phen ligands that provide the N,N,O,O-tetradentate coordination of the phen moiety and two additional N,N-dioxides. The chiral ligands, termed Phen-2NO ligands, incorporate the advantages of both the phen skeleton and the pyrroloimidazolone-based N-oxide moiety, and their electronic and steric properties can be readily tuned through the incorporation of substituents in the aromatic rings of the amide group. These ligands presented a superior performance in the Ni(II)-catalyzed asymmetric Michael-type Friedel–Crafts alkylation reaction of indoles with β,γ-unsaturated α-ketoesters. Excellent yields (up to 93%) and high enantioselectivities (up to 99% ee) are obtained for a wide range of substrates under mild conditions. These results demonstrated the promising potential of the Phen-2NO ligand as an efficient chiral phen ligand. [ABSTRACT FROM AUTHOR]

Here, we demonstrate that the first example of harmaline scaffolds serving as acceptor/acceptor-based N-C-C synthons triggered the ring opening and skeletal reconstruction of 3-vinyl benzofuranones for the construction of a library of skeletally diverse polycyclic harmaline scaffolds. These products were smoothly afforded in up to 77% yield, 420: 1 dr under catalyst-free conditions, and expanded the chemical space of biologically significant harmaline derivative species. All synthetic compounds showed cytotoxic activity against tumor cells, especially compound 3at, which exhibited selective cytotoxicity against A549 cells and lower cytotoxicity against normal cells MRC-5 and HK-2. In further mechanism research, 3at inhibited A549 cell proliferation through the G1 phase arrest, induced A549 cell apoptosis through internal and external apoptosis pathways, and suppressed the migration and invasion abilities of A549 cells. These data indicated that compound 3at is the most effective compound in the series and can serve as a promising precursor for drug development. [ABSTRACT FROM AUTHOR]

The development of chiral ligands to fine-tune stereocontrol in asymmetric catalysis is of great demand. To diversify the Py-2NO ligand library recently developed by our group, herein, we synthesized six new Py-2NO ligands, determined the absolute configuration via X-ray crystallographic study of ligand L1g, and applied these ligands in the Ni(II)-catalyzed asymmetric Michael addition reaction of indoles and β,γ-unsaturated α-keto esters. Excellent yields (up to 93%) and high enantioselectivities (up to 99% ee) were obtained for a wide range of substrates under mild conditions. In addition, we discovered the presence of axial chirality in the C(aryl)–N(amide) bond in the tertiary amine-derived N-oxide product via X-ray crystallographic study. Owing to the intriguing characteristics of atropisomerism, we believe that this reaction will add an important member to the axial chiral family. [ABSTRACT FROM AUTHOR]

Herein, previously unreported trimethylindolenines serving as useful C–N synthons in [3+2] cycloaddition reactions of donor–acceptor 3-isothiocyanato oxindoles to build a library of spiro[oxindole-thioxoimidazolidine-indoline] hybrids are described. A wide range of intriguing and complex products bearing three pharmacophores and three adjacent quaternary stereocentres were smoothly afforded in up to 92% yield, >20 : 1 dr, under catalyst-free conditions. Moreover, this strategy further expands the skeletal diversity of polyheterocycles, which will aid the search for new bioactive molecules. [ABSTRACT FROM AUTHOR]

The H2O-promoted controllable synthesis of diverse nitrogen heterocycles from readily available feedstocks was developed by a hydride transfer strategy. A variety of 3-carboxyl and 3-acyl substituted tetrahydroquinolines and 3,4-dihydroquinolin-2(1H)-ones were obtained via cascade Knoevenagel condensation/[1,5]-hydride transfer/cyclization/hydrolysis/decarboxylation and cascade Knoevenagel condensation/[1,5]-hydride transfer/N-dealkylation/N-acylation processes, respectively. In addition, the synthetic utility of the methodology and mechanistic studies were also well presented. [ABSTRACT FROM AUTHOR]

Designing a smart hydrogel to accelerate skin tissue regeneration at wound sites and restore the tissue function is highly desirable in clinical applications. In this study, a series of hydrogels with promising antioxidative and antibacterial traits based on recombinant human collagen type III (rhCol III), which is an emerging biomaterial, and chitosan (CS) were fabricated. The rhCol III-CS hydrogel could realize rapid gelation at wound locations and completely cover irregular wounds. Additionally, the hydrogel facilitated the proliferation and migration of cells and showed potent antibacterial efficacy against both strains, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro. Significantly, the rhCol III-CS2 hydrogel increased the deposition of collagen, thereby accelerating full-thickness wound healing. Collectively, this bioinspired hydrogel was a promising multifunctional dressing to reconfigure the damaged tissue without additional drugs, exogenous cytokines, or cells, providing an effective strategy for the repair and regeneration of skin wounds. [ABSTRACT FROM AUTHOR]

Herein, previously unreported Fischer's base reactants serving as useful 2C building blocks in (3+2) cycloaddition reactions to build a library of bispiro[Fischer's base-oxindole] hybrids are described. These structurally intriguing products containing three adjacent quaternary stereocentres were smoothly afforded in up to 82% yield and >20 : 1 dr under catalyst-free conditions. Notably, the present protocol firstly employs 3-isothiocyanato oxindole serving as an acceptor and then as a donor in the formal (3+2) cycloadditions, allowing practical, straightforward access to structurally diverse cycloadducts. This work expands the applicability scope of 3-isothiocyanato oxindoles, which have been limited to behaving as donor/acceptor-based synthons in cycloadditions in previous work. [ABSTRACT FROM AUTHOR]

Here, we demonstrate the first example of natural product harmaline and its derivatives serving as useful N–C synthons in formal [3+2] cycloadditions with isothiocyanates for the construction of a library of spiropolycyclic harmaline-based hybrids containing two adjacent quaternary stereocentres. These products were smoothly afforded in up to 90% yield, 20 : 1 dr with Et3N as the catalyst under mild conditions. To the best of our knowledge, this also represents the first example of the synthesis of natural product harmaline-based spiropolycyclic scaffolds, and expands the chemical space of biologically significant harmaline derivative species. The newly synthesized structurally diverse compounds were evaluated for their in vitro anticancer activities. These studies indicate that some compounds displayed good anticancer activity against three tumor cells (A549, K562, and PC-3). Among them, compound 3cb displayed the best activity when applied to A549, which is similar to that of cisplatin. Preliminary mechanistic studies indicate that compound 3cb induces apoptosis in A549 cells through a caspase-dependent pathway. These results show that compound 3cb can be prepared as a good lead for drug development. [ABSTRACT FROM AUTHOR]

The compound [(Nb6O19)@Ag34(tBuCC)24(CH3COO)2] (Ag34) was synthesized using the solvothermal method combined with volatilization. This was the first case, to the best of our knowledge, of isolating a silver cluster containing a polyoxoniobate (PONb) template. The luminescence, solution behavior and solid-state stability of Ag34 were studied in detail. Electrospray ionization mass spectrometry indicated that Ag34 can maintain the integrity of its skeleton in solution. Detection of temperature could be a potential application of its unique luminescent behavior. We expect this work to inspire further fabrications of PONb-templated high-nuclearity silver clusters. [ABSTRACT FROM AUTHOR]

A substrate-dependent, highly β-regioselective one-pot multicomponent 1,3-dipolar cycloaddition reaction of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles with azomethine ylides (thermally generated in situ from ninhydrin and sarcosine) is reported for the first time, furnishing a library of biologically useful bispiro[oxindole-isoxazole-indandione] hybrids. Target novel and structurally complex compounds have been obtained in good yields and diastereoselectivities (up to 91% yield and 20 : 1 dr) with two adjacent spiro quaternary centres. Furthermore, the described method, which is different from our previous work of α-regioselective cycloaddition of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles, is a highly β-regioselective cycloaddition. The newly synthesized compounds potently inhibited the proliferation of various cancer cell lines. The most potent compound 4ah could induce the apoptosis of K562 cells through a caspase-dependent and -independent pathway. [ABSTRACT FROM AUTHOR]

Herein, a highly efficient strategy that allows the diverse synthesis of a library of structural bispiro[butyrolactone–pyrrolidine–indanedione] hybrids is achieved effectively for the first time by means of 1,3-dipolar cycloadditions of α,β-unsaturated butyrolactones/valerolactones as dipolarophiles with azomethine ylides (thermally generated in situ from ninhydrin and proline or thioproline) via an exo′-transition state. Potentially bioactive target compounds have been obtained in good yields and diastereoselectivities (up to 89% yield and all cases >20 : 1 dr). [ABSTRACT FROM AUTHOR]

The first example of ring-opening and recyclization reaction of 3-vinyl oxindole-chromones 1 as versatile synthons, which can react with ammonia or primary aliphatic amines as binucleophiles is developed, serving as a fruitful strategy for the eco-friendly and atom-economic synthesis of a new family of skeletally diverse 2-hydroxy benzoyl pyridones 3 with high to excellent yields (70–92%). The advantages of this methodology, including the use of easily available raw materials and the catalyst-free, wide functional group tolerance, and gram-scale synthesis, make the developed methodology a practical way to access important biologically active 2-hydroxy benzoyl pyridone molecules. [ABSTRACT FROM AUTHOR]

A metal-/catalyst-free protocol for the direct thioamination of 1,4-naphthoquinone with thiophenols and amines using air as an oxidant in a green solvent has been developed. This environmentally friendly strategy was realized using commercially available reagents with simple operation under mild conditions affording 2-amino-3-thio-1,4-naphthoquinones as products in moderate to good yields. Importantly, the use of cyclopentyl methyl ether (CPME) as a solvent could eliminate the need for traditional amide solvents with tedious post-treatment. Additionally, the potential utility of this protocol was further demonstrated by a gram-scale experiment. [ABSTRACT FROM AUTHOR]

A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs. [ABSTRACT FROM AUTHOR]

A new type of bifunctional 3C synthon, a chromone–indanedione precursor, was employed for diastereoselective Michael/Michael cycloaddition with methyleneindolinones to generate a series of potentially bioactive bispiro-[chromanocyclopentane-oxindole-indanedione] frameworks with skeletal diversity in a single operation. This reaction exhibited good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities via an endo-transition state (up to 78% yield and >20 : 1 diastereomeric ratio). In particular, this reaction is the first example of using a chromone–indanedione precursor as a bifunctional 3C synthon, the first example of the construction of bispiro-chromanocyclopentanes, and also the first example of the introduction of a chromanocyclopentane moiety into spiroindanone frameworks, which might be valuable in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Inspired by the chemistry and biology of hexahydroxanthones, herein we report an organocatalytic Michael–Michael–Aldol-decarboxylation reaction that provides efficient access to biologically interesting fully substituted hexahydroxanthones bearing six contiguous stereogenic centers from readily accessible materials in acceptable yields (up to 63%) and excellent stereoselectivities (up to 10 : 1 dr and >99% ee). In other words, the reaction efficiently produces three chemical bonds and up to six vicinal stereogenic centers in a one-pot operation. In particular, to our knowledge, this is an asymmetric organocatalytic strategy enabling the first construction of six vicinal stereogenic centers on non-spirocyclic hexahydroxanthone frameworks. [ABSTRACT FROM AUTHOR]

The direct use of ammonium hydroxide in amination for the synthesis of primary amines is considered to be one of the major challenges in synthetic organic chemistry. Herein, the first example of catalyst-free direct amination of 3-halooxindoles with ammonium hydroxide to synthesize N-unprotected 3-tetrasubstituted aminooxindoles in high yields (up to 91% yield) is described. An enhancement of the reaction rate on using water was observed under mild conditions. Such an approach is not only protection/deprotection-free, but also more practical and cost-effective. Moreover, this method could expand the library of 3-tetrasubstituted aminooxindole building blocks for the further synthesis of AG-041R, GHSR antagonists and a charteline unit, opening up a new synthetic pathway in the chemistry of 3-aminooxindoles. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) is a typical reactive peroxide that is widely used in food preservation but may cause serious harm to human health. Thus, a simple, efficient and accurate method for H2O2 assay is essential. In this work, a dual Eu-MOFs-based ratiometric fluorescence sensor, a logic gate-based advanced analytical method, and a dual MOFs-loaded paper microchip for visual H2O2 assay were constructed. The H2O2 sensor was response-sensitive (limit of detection: 0.14 μM) and linearly responsive in the concentration range of 0.001–1 mM (r > 0.99). Then, an advanced AND gate logic device was established to monitor H2O2 concentration. Moreover, the paper-based microchip realized the point-of-care visual H2O2 assay via ratiometric chromaticity assisted by a portable smartphone-based visual assay device. The microchip consumes only 5 μL of sample and demonstrates long-term stability for over 30 days along with response-sensitivity. Both the MOF dispersion-based ratiometric fluorescence sensor and the paper microchip realized an accurate and precise assay of H2O2 (the recovery was 88.2–105.5% and RSD < 9.3%). To the best of our knowledge, this is the first report of a dual MOFs-based ratiometric fluorescent H2O2 sensor, an advanced logic gate-based analytical method, and a paper-based microchip for visual point-of-care H2O2 assay. [ABSTRACT FROM AUTHOR]

The first example of a bifunctional donor–donor 3C synthon in situ from activated methine (methyleneindolinone and methylenebenzofuranone) with nitromethane through a [2+1] Michael addition, which further directed the following organocascade Michael/Henry cycloaddition reaction in a one-pot operation is developed, serving as a fruitful strategy for facile access to optically active and structurally diverse hexahydroxanthones with up to six contiguous stereocenters, including a quaternary one. A series of diversely functionalized products are smoothly obtained with up to 76% yield, >20 : 1 d.r. and 98% ee from simple and readily available starting materials. In addition, this is the first example of 3-formyl chromone as an acceptor–acceptor 3C building block, and also the first asymmetric catalytic construction of six vicinal stereogenic centers on a hexahydroxanthone scaffold. [ABSTRACT FROM AUTHOR]

A cyclometalated iridium(iii) complex (Ir-DNBS) was designed and synthesized as a high-performance phosphorescent thiophenol probe. Ir-DNBS displays a distinct phosphorescence “off–on” response toward thiophenol with high selectivity, high sensitivity (detection limit: 2.5 nM) and fast response (10 min). It is noteworthy that the signaling phosphore of Ir-DNBS possesses relatively high photoluminescence quantum efficiency (ΦPL = 0.21) together with relatively long lifetime (τ = 2.07 μs), indicative of its potential in achieving high temporal resolution. Ir-DNBS is also applicable to the detection of thiophenol in actual water samples with high recovery rate. Photophysical and spectral characterization results revealed that the probing mechanism of Ir-DNBS toward thiophenol lies in the thiolate-mediated cleavage reaction, resulting in suppressed photo-induced excited state electron transfer process in the reaction product. [ABSTRACT FROM AUTHOR]

The structural stability, electronic and optical properties of α-Si3N4 nanobelts orientating along the different directions with surface H, F and Cl modifications are investigated using first-principles methods. The stabilities of α-Si3N4 nanobelts are greatly affected by the surface modifications and increased in the order of H, Cl and F. All the modified α-Si3N4 nanobelts exhibit semiconductor characteristics. The effective masses of nanobelts are mainly affected by their orientations as well as surface modifications. The band gaps of α-Si3N4 nanobelts are found to be modulated by surface modifications. The Cl-modified nanobelts result in a smaller band gap than that of H- or F-modified ones. The electronic properties of α-Si3N4 nanobelts have significantly affected their optical properties. The linear light response ranges are mainly located in the ultraviolet region, where the absorption and refraction of light mainly occur, while the reflection is very weak. As the halogen coverage increases to 100%, the absorption edges of α-Si3N4 nanobelts have an obvious red-shift and new dielectric peaks appear. The Cl-modified nanobelts possess higher ε2(̉) peaks, lower absorption edges and better photoelectric characteristics than those of H- or F-modified nanobelts. The static optical parameters ε(0) and n(0) of 100% Cl-modified α-Si3N4 nanobelts are significantly larger than those of other nanobelts, indicating special applications in certain optical components. [ABSTRACT FROM AUTHOR]

The energetic stability and electronic properties of unpassivated, hydrogen (–H) and hydroxyl (–OH) passivated α-Si3N4 nanobelts orientating along the [101], [210], [011], [100], [001], and [110] directions are investigated by first-principles calculations. Calculations show that the energetic stabilities of α-Si3N4 nanobelts depend weakly upon orientations of nanobelts, but sensitively on passivation treatments. The most stable nanobelt is the OH cluster partially passivated α-Si3N4, followed by the H atom fully passivated and the unpassivated systems. All the unpassivated nanobelts show metallic characteristics due to the presence of dangling bonds of surficial atoms in nanobelts, while all the passivated nanobelts exhibit semiconducting characteristics. The valence band maximum (VBM) and the conduction band minimum (CBM) mainly originate from the surface N-2p and Si-3p states, respectively. For α-Si3N4 nanobelts orientating along [101], [210], [011] and [110] directions, the OH passivated systems exhibit a much smaller band gap than the H passivated systems, while the [100] and [001] orientated nanobelts exhibit the opposite band-gap properties. [ABSTRACT FROM AUTHOR]

Neuronal growth cones contain sophisticated molecular machinery precisely regulating their migration in response to complex combinatorial gradients of diverse external cues. The details of this regulation are still largely unknown, in part due to limitations of the currently available experimental techniques. Microfluidic devices have been shown to be capable of generating complex, stable and precisely controlled chemical gradients, but their use in studying growth cone migration has been limited in part due to the effects of shear stress. Here we describe a microfluidics-based turning-assay chip designed to overcome this issue. In addition to generating precise gradients of soluble guidance cues, the chip can also fabricate complex composite gradients of diffusible and surface-bound guidance cues that mimic the conditions the growth cones realistically counter in vivo. Applying this assay to Xenopus embryonic spinal neurons, we demonstrate that the presence of a surface-bound laminin gradient can finely tune the polarity of growth cone responses (repulsion or attraction) to gradients of brain-derived neurotrophic factor (BDNF), with the guidance outcome dependent on the mean BDNF concentration. The flexibility inherent in this assay holds significant potential for refinement of our understanding of nervous system development and regeneration, and can be extended to elucidate other cellular processes involving chemotaxis of shear sensitive cells. [ABSTRACT FROM AUTHOR]

A selective arylation of donor-acceptor diazo compounds with aniline derivatives catalyzed by Lewis acidic boranes is developed. This simple reaction protocol provides an efficient method for the synthesis of diarylacetates under metal-free conditions.

The structural stability, electronic and optical properties of α-Si3N4 nanobelts orientating along the different directions with surface H, F and Cl modifications are investigated using first-principles methods. The stabilities of α-Si3N4 nanobelts are greatly affected by the surface modifications and increased in the order of H, Cl and F. All the modified α-Si3N4 nanobelts exhibit semiconductor characteristics. The effective masses of nanobelts are mainly affected by their orientations as well as surface modifications. The band gaps of α-Si3N4 nanobelts are found to be modulated by surface modifications. The Cl-modified nanobelts result in a smaller band gap than that of H- or F-modified ones. The electronic properties of α-Si3N4 nanobelts have significantly affected their optical properties. The linear light response ranges are mainly located in the ultraviolet region, where the absorption and refraction of light mainly occur, while the reflection is very weak. As the halogen coverage increases to 100%, the absorption edges of α-Si3N4 nanobelts have an obvious red-shift and new dielectric peaks appear. The Cl-modified nanobelts possess higher ε2(ω) peaks, lower absorption edges and better photoelectric characteristics than those of H- or F-modified nanobelts. The static optical parameters ε(0) and n(0) of 100% Cl-modified α-Si3N4 nanobelts are significantly larger than those of other nanobelts, indicating special applications in certain optical components.

A highly efficient and environmentally benign method for the synthesis of oxindoles featuring two contiguous quaternary carbon centers via an aldol reaction starting from various 3-substituted oxindoles has been established. A wide variety of such featured multi-substituted 1,3-indandione ring-fused 3-oxindole scaffolds were obtained smoothly in good yields (up to 98%) employing the most green of solvents, namely water, as reaction medium. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by MTT-based assays, using the commercially available standard drug, cisplatin, as a positive control. Gratifyingly, compounds 3s, 3u, 3y and 3c' exhibited the best levels of in vitro inhibitory activity against human leukemia cells K562, which were almost 2.0, 2.8, 2.5 and 2.2 times, respectively, the activity of the positive control, cisplatin. Compound 3y had 2.7 times the activity of the positive control, cisplatin, against PC-3 cancer cells, and 3s, 3u and 3c' showed levels of in vitro inhibitory activity against PC-3 cancer cells that were comparable to that of cisplatin. Compounds 3s, 3u and 3y had good inhibitory ability against human lung cancer cells A549. The results indicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads for further biological screenings.

The energetic stability and electronic properties of unpassivated, hydrogen (-H) and hydroxyl (-OH) passivated α-Si3N4 nanobelts orientating along the [101], [210], [011], [100], [001], and [110] directions are investigated by first-principles calculations. Calculations show that the energetic stabilities of α-Si3N4 nanobelts depend weakly upon orientations of nanobelts, but sensitively on passivation treatments. The most stable nanobelt is the OH cluster partially passivated α-Si3N4, followed by the H atom fully passivated and the unpassivated systems. All the unpassivated nanobelts show metallic characteristics due to the presence of dangling bonds of surficial atoms in nanobelts, while all the passivated nanobelts exhibit semiconducting characteristics. The valence band maximum (VBM) and the conduction band minimum (CBM) mainly originate from the surface N-2p and Si-3p states, respectively. For α-Si3N4 nanobelts orientating along [101], [210], [011] and [110] directions, the OH passivated systems exhibit a much smaller band gap than the H passivated systems, while the [100] and [001] orientated nanobelts exhibit the opposite band-gap properties.