Asymmetric Hydrative Aldol Reaction (HAR) via Vinyl-Gold Promoted Intermolecular Ynamide Addition to Aldehydes.

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to ß-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee).

Tongalides, Halogenated Butenolides from an Antarctic Delisea sp. Rhodophyte.

Six new halogenated butenolides, tongalides A-C (1-3) and their acetylated congeners (4-6), were isolated from an extract of the Antarctic rhodophyte Delisea sp. that displayed significant antibiotic activity. The structures of the compounds were determined by analysis of data acquired by spectroscopic and spectrometric techniques including NMR, HRESIMS, optical rotation, and X-ray diffraction studies. The newly isolated compounds were assayed for antibacterial activity, but exhibited no growth inhibition of ESKAPE pathogens. The extract bioactivity was attributed to the previously reported Z-acetoxyfimbrolide A also isolated from the extract, providing further evidence that the exocyclic double bond is essential to the antibacterial activity of the structurally related fimbrolide class of metabolite.

Metallo-Supramolecular Octahedral Cages with Three Types of Chirality towards Spontaneous Resolution.

Chirality is one of the most important intrinsic properties of (supra)molecules. In this study, we obtained enantiomeric metallo-supramolecular octahedra without using any chiral sources. Such cages were self-assembled by prochiral trispyridine ligand L based on a C3h truxene core and CuII salts. Crystallization of the cages with BF4 - as counterions afforded racemate crystals; while crystallizations of cages with ClO4 - and OTf- as counterions resulted in conglomerates with spontaneous resolution. Three types of chirality were observed in each cage, including planar chirality of the truxene core, axial chirality from the pyridyl and truxene moieties, and propeller chirality of the pyridyl-CuII coordination sites. The cages reported here are among the largest discrete synthetic metallo-supramolecules ever reported with chiral self-sorting behavior. Remarkably, the chiral cages exhibited very slow racemization even at low concentrations, suggesting their high stability in solution.

Alkyne Trifunctionalization via Divergent Gold Catalysis: Combining π-Acid Activation, Vinyl-Gold Addition, and Redox Catalysis.

Here we report the first example of alkyne trifunctionalization through simultaneous construction of C-C, C-O, and C-N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl-gold nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both electrophiles (N source) and oxidants (C source). Vinyl-gold(III) intermediates were revealed as effective nucleophiles toward diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature or 40 °C).

Construction of Stable Helical Metal-Organic Frameworks with a Conformationally Rigid "Concave Ligand".

A helical metal-organic framework was prepared by using a conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups were applied to introduce atropic repulsion, thereby allowing the formation of extended frameworks for the first time. With this new ligand design, a helical-shaped MOF with significantly improved air and moisture stability was successfully prepared, thus providing a new strategy for ligand design toward porous material constructions.

Highly Stable Single Crystals of Three-Dimensional Porous Oligomer Frameworks Synthesized under Kinetic Conditions.

Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water.

Conformational Control of a Metallo-Supramolecular Cage via the Dissymmetrical Modulation of Ligands.

In nature as well as life systems, the presence of asymmetrical and dissymmetrical structures with specific functions is extremely common. However, the construction of metallo-supramolecular assemblies based on dissymmetrical ligands still remains a considerable challenge for avoiding the generation of unexpected isomers with similar thermodynamic stabilities, especially for three-dimensional supramolecular structures. In this study, a strategy for the conformational control of metallo-supramolecular cages via the enhancement of ligand dissymmetry was proposed. Four dissymmetrical ditopic ligands were designed and synthesized. By increasing the dissymmetry of length or angle, conformations of assemblies were precisely controlled to form discrete cis-Pdn L2n molecular cages.

Functional Porphyrinic Metal-Organic Framework as a New Class of Heterogeneous Halogen-Bond-Donor Catalyst.

Biomimetic metal-organic frameworks have attracted great attention as they can be used as bio-inspired models, allowing us to gain important insights into how large biological molecules function as catalysts. In this work, we report the synthesis and utilization of such a metal-metalloporphyrin framework (MMPF) that is constructed from a custom-designed ligand as an efficient halogen bond donor catalyst for Diels-Alder reactions under ambient conditions. The implementation of fabricated halogen bonding capsule as binding pocket with high-density C-Br bonds enabled the use of halogen bonding to facilitate organic transformations in their three-dimensional cavities. Through combined experimental and computational studies, we showed that the substrate molecules diffuse through the pores of the MMPF, establishing a host-guest system via the C-Br⋅⋅⋅π interaction. The formation of halogen bonds is a plausible explanation for the observed boosted catalytic efficiency in Diels-Alder reactions. Moreover, the unique capability of MMPF highlights new opportunities in using artificial non-covalent binding pockets as highly tunable and selective catalytic materials.

A MOF-based Ultra-Strong Acetylene Nano-trap for Highly Efficient C2 H2 /CO2 Separation.

Porous materials with open metal sites have been investigated to separate various gas mixtures. However, open metal sites show the limitation in the separation of some challenging gas mixtures, such as C2 H2 /CO2 . Herein, we propose a new type of ultra-strong C2 H2 nano-trap based on multiple binding interactions to efficiently capture C2 H2 molecules and separate C2 H2 /CO2 mixture. The ultra-strong acetylene nano-trap shows a benchmark Qst of 79.1 kJ mol-1 for C2 H2 , a record high pure C2 H2 uptake of 2.54 mmol g-1 at 1×10-2  bar, and the highest C2 H2 /CO2 selectivity (53.6), making it as a new benchmark material for the capture of C2 H2 and the separation of C2 H2 /CO2 . The locations of C2 H2 molecules within the MOF-based nanotrap have been visualized by the in situ single-crystal X-ray diffraction studies, which also identify the multiple binding sites accountable for the strong interactions with C2 H2 .

Gold Redox Catalysis with a Selenium Cation as a Mild Oxidant.

Gold-catalyzed alkyne and allene diselenations were developed. Excellent regioselectivity (trans) and good to excellent yields were achieved (up to 98 % with 2 % catalyst loading) with a wide range of substrates. Mechanistic investigation revealed the formation of a vinyl gold(I) intermediate followed by an intermolecular selenium cation migration, suggesting that a gold(I/III) redox process was successfully implemented under mild conditions.

"Orthogonal-Twisted-Arm" Ligands for The Construction of Metal-Organic Frameworks (MOFs): New Topology and Catalytic Reactivity.

Extended tetratopic benzoic acid ligands with "orthogonal-twisted-arms" conformations were designed and synthesized for the construction of new MOF structures (OTA-MOF). Upon coordination with Cd2+ and Cu2+ cations, two well-defined new MOFs were prepared. X-ray single crystal structures were successfully obtained, demonstrating the formation of a new topology (4,4,4-c). The OTA2-MOF-Cu gave moderate stability in organic solvents and good gas sorption ability toward CO2 . This new MOF showed superior catalytic reactivity toward the epoxide-CO2 cycloaddition, giving >50 folds yield enhancement over the controlled reaction without MOF. It is expected that this new ligand design, porous structure, and excellent CO2 catalytic reactivity will make OTA-MOF promising new materials for applications in catalysis and separation.

Diagnostic value of GLUT-1 in distinguishing malignant mesothelioma from reactive mesothelial cells: a meta-analysis.

Background: Previous studies have demonstrated the diagnostic value of glucose transporter 1 (GLUT-1) to distinguish malignant mesothelioma (MM) from reactive mesothelial cells (RMC), but the results are inconsistent. The purpose of this meta-analysis is to investigate the diagnostic accuracy of GLUT-1 in distinguishing MM from RMC.Methods: A systematical search was conducted until May 2019 in PubMed, Medline, Embase and the Cochrane Library. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess the quality of the eligible studies. The Stata15 and Review Manager5.3 software programmes were used to perform the meta-analysis.Results: A total of 24 studies, including 969 MM patients and 1080 RMC individuals were explored in the meta-analysis. The summary assessments revealed that the pooled sensitivity was 0.73 (95% CI, 0.62-0.81) and the pooled specificity was 0.95 (95% CI, 0.91-0.98). The area under the summary ROC curve (AUC) was 0.93 (95% CI: 0.91-0.95).Conclusions: GLUT-1 is highly accurate to distinguish MM from RMC.

Self-Assembly of Porphyrin-Containing Metalla-Assemblies and Cancer Photodynamic Therapy.

In this report, we describe the synthesis of two porphyrin-containing Pt(II) supramolecular assemblies via coordination-driven self-assembly. X-ray crystallographic analysis on one assembly reveals that the metalla-assembly formation imposes large interchromophore distances, leading to a higher 1O2 generation efficiency, relative to the corresponding small molecular precursors. The metalla-assemblies were examined as photosensitizers for photodynamic therapy as the potential reduction of the unfavorable self-aggregation phenomenon. In vivo and in vitro investigations demonstrate that the metalla-assemblies exhibit enhanced anticancer activity with minimal dose requirement and side effects comparable to the small molecule precursors. Thus, our work demonstrates that self-assembly provides a promising methodology for enhancing the therapeutic effectiveness of anticancer agents.

A Porous Organic Polymer Nanotrap for Efficient Extraction of Palladium.

To offset the environmental impact of platinum-group element (PGE) mining, recycling techniques are being explored. Porous organic polymers (POPs) have shown significant promise owing to their selectivity and ability to withstand harsh conditions. A series of pyridine-based POP nanotraps, POP-Py, POP-pNH2 -Py, and POP-oNH2 -Py, have been designed and systematically explored for the capture of palladium, one of the most utilized PGEs. All of the POP nanotraps demonstrated record uptakes and rapid capture, with the amino group shown to be vital in improving performance. Further testing on the POP nanotrap regeneration and selectivity found that POP-oNH2 -Py outperformed POP-pNH2 -Py. Single-crystal X-ray analysis indicated that POP-oNH2 -Py provided a stronger complex compared to POP-pNH2 -Py owing to the intramolecular hydrogen bonding between the amino group and coordinated chlorine molecules. These results demonstrate how slight modifications to adsorbents can maximize their performance.

A Corrole-Based Covalent Organic Framework Featuring Desymmetrized Topology.

Herein, for the first time, we present the successful synthesis of a novel two-dimensional corrole-based covalent organic framework (COF) by reacting the unusual approximately T-shaped 5,10,15-tris(p-aminophenyl)corrole H3 TPAPC with terephthalaldehyde, which adopts desymmetrized hcb topology and consists of a staggered AB stacking structure with elliptical pores. The resultant corrole-based COF, TPAPC-COF, exhibits high crystallinity and excellent chemical stability. The combination of extended π-conjugated backbone and interlayer noncovalent π-π interactions endows TPAPC-COF with excellent absorption capability in the entire visible-light and even near-infrared regions. Moreover, this work suggests the promise of TPAPC-COF as a new class of photoactive material for efficient singlet-oxygen generation with potential photodynamic therapy application as demonstrated by in vitro anticancer studies.

Robust Corrole-Based Metal-Organic Frameworks with Rare 9-Connected Zr/Hf-Oxo Clusters.

The corrole unit from the porphyrinoid family represents one of the most important ligands in the field of coordination chemistry, which creates a unique environment allowing for the observation of unusual electronic states of bound metal cations and has shown great promise in various applications. Nevertheless, studies that directly and systematically introduce these motifs in porous crystalline materials for targeting further functionalizations are still lacking. Herein, we report for the first time the construction of two robust corrole-based metal-organic frameworks (MOFs), M6(µ3-O)4(µ3-OH)4(OH)3(H2O)3(H3TCPC)3 (M = Zr for Corrole-MOF-1 and M = Hf for Corrole-MOF-2, H3TCPC = 5,10,15-tris(p-carboxylphenyl)corrole), which are assembled by a custom-designed C2ν-symmetric corrolic tricarboxylate ligand and the unprecedented D3d-symmetric 9-connected Zr6/Hf6 clusters. The resultant frameworks feature a rare (3,9)-connected gfy net and exhibit high chemical stability in aqueous solutions within a wide range of pH values. Furthermore, we successfully prepared the cationic Corrole-MOF-1(Fe) from the iron corrole ligand, which can serve as an efficient heterogeneous catalyst for [4 + 2] hetero-Diels-Alder reactions between unactivated aldehydes and a simple diene, outperforming both the homogeneous counterpart and the porphyrinic MOF counterpart.

Facilitating Gold Redox Catalysis with Electrochemistry: An Efficient Chemical-Oxidant-Free Approach.

Due to the high oxidation potential between AuI and AuIII , gold redox catalysis requires at least stoichiometric amounts of a strong oxidant. We herein report the first example of an electrochemical approach in promoting gold-catalyzed oxidative coupling of terminal alkynes. Oxidation of AuI to AuIII was successfully achieved through anode oxidation, which enabled facile access to either symmetrical or unsymmetrical conjugated diynes through homo-coupling or cross-coupling. This report extends the reaction scope of this transformation to substrates that are not compatible with strong chemical oxidants and potentiates the versatility of gold redox chemistry through the utilization of electrochemical oxidative conditions.

Preparation of Silver Nanowires with High Aspect Ratio and Influence of Reaction Conditions on the Morphology Size.

Silver nanowires with high yield, uniform size and high aspect ratio were successfully synthesized by a simple and effective polyol method under low temperature and quiescent conditions, adopting CuCl2·2H2O as the nucleation control agent for the first time. The synthesized silver nanowires were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Vis diffuse reflectance spectroscopy (DRS). The results indicate that the silver nanowires were composed of face-centered cubic structure of pure metallic silver with high crystallinity. And the silver nanowires have an average length of 80~100 µm and an average diameter of 40~80 nm. Thus, the aspect ratio of the nanowires was greater than 1000. In addition, the influence on the morphology and structure of the silver nanowires were investigated for reaction temperature, mole ratio of PVP:AgNO3, molecular weight of PVP and mole ratio of control agent CuCl2 · 2H2O:AgNO3. Finally, the optimum reaction condition were obtained for the preparation of the silver nanowires with high aspect ratio.

Recombinant EGFR/MMP-2 bi-targeted fusion protein markedly binding to non-small-cell lung carcinoma and exerting potent therapeutic efficacy.

Overexpression of EGFR and MMP-2 plays an essential role in the initiation and progression of non-small-cell lung carcinoma (NSCLC). In this study, a novel format of EGFR/MMP-2 bi-targeted fusion protein Ec-LDP-TIMP2 and its enediyne-integrated analogue Ec-LDP(AE)-TIMP2 have been prepared by genetic engineering and molecular reconstitution. The Ec-LDP(AE)-TIMP2 comprises endogenous inhibitor of matrix metalloproteinase 2 (TIMP2), EGF-derived oligopeptide (Ec), lidamycin apoprotein (LDP), and the extremely potent cytotoxic enediyne (AE). By tissue microarray, Ec-LDP-TIMP2 showed high binding intensity and selectivity to human NSCLC specimens as compared with the matched non-cancerous tissues. By in vivo imaging, Ec-LDP-TIMP2 displayed prominent tumor-specific distribution in human NSCLC H460 xenograft. Particularly, Ec-LDP(AE)-TIMP2 inhibited tumor growth of H460 xenograft in athymic mice more striking. At doses of 0.2 and 0.4mg/kg, Ec-LDP(AE)-TIMP2 suppressed tumor growth by 74% and 89%, respectively. No histopathological changes were found in various organs of treated animals, suggesting that the effective dosage was tolerated. In summary, the ligand-based and enediyne-integrated fusion protein displaying extremely potent cytotoxicity might be highly effective for NSCLC therapy and useful as a carrier for drug delivery.

Two novel cyclic hexapeptides from the genetically engineered Actinosynnema pretiosum.

Two novel cyclic hexapeptides designated actinosynneptides A (1) and B (2), together with three tryptophan containing diketopiperazines, namely cyclo(L-Trp-L-Trp) (3), cyclo(L-Trp-N-MeL-Trp) (4), and cyclo(N-MeL-Trp-N-MeL-Trp) (5), were isolated from the culture of the genetically engineered strain HGF052::asm18 derived from Actinosynnema pretiosum ATCC31565. Their structures were elucidated on the basis of spectroscopic analyses and single-crystal X-ray diffractions. Compound 1 is the first example of 3-amino-6-hydroxy-2-piperidone-containing cyclic peptides, and 1 and 2 showed moderate cytotoxic activities against HeLa and PC3 cell lines.