Angewandte Chemie International Edition

Molecular dynamics of hexamethylbenzene at low temperatures; evidence of unconventional magnetism based on rotational motion of protons ()
The types of magnetism known to date are all mainly based on contributions from electron motion. We show how rotational motion of protons (H+) within the methyl groups in hexamethylbenzene (C6(CH3)6) also contribute significantly to the magnetic susceptibility. Starting from below 118 K, as the rotational motion of the methyl groups set in, an associated magnetic moment positive in nature due to charge of the protons renders the susceptibility to become anomalously dependent on temperature. Starting from 20 K, the susceptibility diverges with decreasing temperature indicative of spin-spin interactions between methyl groups aligned in a previously unclassified type of anti-ferromagnetic configuration. Complementary dielectric constant measurements also show the existence of magneto-dielectric coupling. Our findings allow for the study of strongly correlated systems that are based on a species that possesses much slower dynamics.
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A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly-Substituted Methylene Azetidines ()
The reaction of rhodium-bound carbenes with strained bicyclic methylene aziridines results in a formal [3+1] ring expansion to yield highly-substituted methylene azetidines with excellent regio- and stereoselectivity. The reaction appears to proceed through an ylide-type mechanism, where the unique strain and structure of the methylene aziridine promotes a ring-opening/ring-closing cascade that efficiently transfers chirality from substrate to product. The resultant products can be elaborated into new azetidine scaffolds containing vicinal tertiary-quaternary and even quaternary-quaternary stereocenters.
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Electroless Formation of Hybrid Lithium Anodes for Fast Interfacial Ion Transport ()
Rechargeable batteries based on metallic anodes are of interest for fundamental and applications-focused studies of chemical and physical kinetics of liquids at solid interfaces. Approaches that allow facile creation of uniform coatings on these metals to prevent physical contact with liquid electrolytes, while enabling fast ion-transport, are essential to address chemical instability of the anodes. Here, we report a simple electroless ion-exchange chemistry for creating coatings of the metal Indium on lithium. By means of Joint-Density Functional theory and interfacial characterization experiments, we show that In coatings stabilize Li by multiple processes, including enabling exceptionally fast surface diffusion of lithium ions and high chemical resistance to liquid electrolytes. Indium coatings also undergo reversible alloying reactions with lithium ions, facilitating design of high-capacity hybrid In-Li anodes that utilize both alloying and plating chemistries for charge storage.
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Enzymatic C-H Amidation in the Production of Natural and Unnatural Thiotetronate Antibiotics with Potentiated Bioactivity ()
The selective activation of unreactive hydrocarbons by biosynthetic enzymes has inspired new synthetic methods in C-H bond activation. Herein, we report the unprecedented two-step biosynthetic conversion of thiotetromycin to thiotetroamide C involving the tandem carboxylation and amidation of an unreactive ethyl group. We detail the genetic and biochemical basis for the terminal amidation in thiotetroamide C biosynthesis, which involves a uniquely adapted cytochrome P450-amidotransferase enzyme pair and highlights the first carboxylation-amidation enzymatic cascade reaction leading to the selective formation of a primary amide group from a chemically inert alkyl group. Motivated by the ten-fold increase in antibiotic potency of thiotetroamide C ascribed to the acetamide group and the unusual enzymology involved, we enzymatically interrogated diverse thiolactomycin analogues and prepared an unnatural thiotetroamide C analogue with potentiated bioactivity compared to the parent molecule.
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Anionic Palladium(0) and Palladium(II) Ate Complexes ()
Palladium ate complexes are frequently invoked as important intermediates in Heck and cross-coupling reactions, but so far have largely eluded a characterization at the molecular level. Here, we use electrospray-ionization mass spectrometry, electrical conductivity measurements, and NMR spectroscopy to show that the electron-poor catalyst [L₃Pd] (L = tris[3,5-bis(trifluoromethyl)-phenyl]phosphine) readily reacts with Br− ions to afford the anionic, zero-valent ate complex [L₃PdBr]−. In contrast, more electron-rich Pd catalysts display lower tendencies toward the formation of ate complexes. Combining [L₃Pd] with LiI and an aryl iodide substrate ArI results in the observation of the Pd(II) ate complex [L₂Pd(Ar)I₂]−.
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Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N-Aryl Anthranilamides ()
Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal catalyzed C-N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.
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Osmium-mediated 4sU-to-C transformation as key to study RNA dynamics by sequencing (TUC-seq) ()
To understand the functional roles of RNA in the cell, it is essential to elucidate the dynamics of their production, processing and decay. A recent method for assessing mRNA dynamics is metabolic labeling with 4-thiouridine (4sU), followed by thio-selective attachment of affinity tags. Detection of labeled transcripts by affinity purification and hybridization to microarrays or by deep sequencing then reveals RNA expression levels. Here, we present a novel sequencing method that eliminates affinity purification and allows for direct assessment of 4sU labeled RNA. It employs an OsO4 transformation to convert 4sU into cytosine. We exemplify the utility of the new method for verification of endogenous 4sU in tRNAs and for the detection of pulse-labeled mRNA of seven selected genes in mammalian cells to determine the relative abundance of the new transcripts. The results prove TUC-seq as a straight-forward and highly versatile method for studies of cellular RNA dynamics.
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Regio- and Stereoselective Chlorocyanation of Alkynes ()
The regio- and stereoselective conversion of alkynes into (Z)-3-chloroacrylonitriles was achieved by treatment of a variety of terminal as well as internal alkynes with BCl3 in the presence of stoichiometric amounts of imidazolium thiocyanates. These products can be easily functionalized into useful building blocks, demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid followed by electrophilic attack of the alkyne. syn-Addition of a chloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.
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The Hydrophobic Gap at High Hydrostatic Pressures ()
We gain new insight into the so-called hydrophobic gap, a molecularly thin region of decreased electron density at the interface between water and a solid hydrophobic surface, by X-ray reflectivity experiments and molecular dynamics simulations at different hydrostatic pressures. Pressure variation shows that the hydrophobic gap persists up to a pressure of 5 kbar. The depletion in the interfacial region is strongly decreasing with rising pressure, indicating that the interfacial region is compressed more strongly than bulk water. The decrease is most significant up to 2 kbar, beyond that, the pressure response of the depletion is less pronounced.
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Chemotaxis-Guided Hybrid Neutrophil Micromotor for Actively Targeted Drug Transport ()
Engineering self-propelled micromotors with good biocompatibility and biodegradability for actively seeking sites of diseases and targeted drug transport remains a huge challenge. Here we demonstrate that neutrophils with intrinsic chemotaxis ability could be transformed into self-guided biohybrid motors through integrating mesoporous silica nanoparticles (MSNs) with high loading capability. To realize the compatibility of neutrophil cells with drug-loaded MSNs, bacteria membranes derived from E. coli were coated onto MSNs in advance by using a camouflaging strategy. The resulting biohybrid micromotors successfully inherit the characteristic chemotaxis capability of native neutrophils and could move along the chemoattractant gradients produced by E.coli. Our studies suggest that the camouflaging approaches, which favor the uptake of MSNs into neutrophils without losing cellular activity and motility, could be used to construct biohybrid micromotors for advanced biomedical applications.
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Intracellular Delivery of Functional Native Antibodies under Hypoxic Conditions by Using a Biodegradable Silica Nanoquencher ()
Antibodies are important biopharmaceuticals, but almost all antibody-based drugs are limited to targeting antigens located at the cell exterior due to their inability to enter the cell interior. Available methods for intracellular delivery of antibodies have major shortcomings. Herein we report an approach to encapsulate native antibodies in a biodegradable silica nanoquencher (BS-qNP) which could undergo efficient cellular uptake and intracellular degradation to release antibodies under hypoxic conditions. By coating the surface of BS-qNP with cell-penetrating poly(disulfide)s (CPD), the delivered antibodies (or other proteins) avoided endolysosomal trapping. Doping of the silica coating with a fluorescent dye and a dark hole quencher further endowed BS-qNP with hypoxia-responsive fluorescence Turn-ON property. Our antibody delivery system thus provides the first platform capable of stable encapsulation, efficient uptake, on-demand antibody release and imaging of release/cell state.
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Phosphine-catalyzed Enantioselective Formal [4+4] Annulation of alpha,beta-Unsaturated Imines and Allene Ketones: Construction of Eight-membered Rings ()
The first highly enantioselective phosphine-catalyzed formal[4+4] annulation has been developed. In the presence of amino acid-derived phosphines, the unprecedented formal [4+4] annulations between benzofuran/indole derived α,β-unsaturated imines and allene ketones proceeded smoothly, affording azocines bearing a benzofuran or an indole moiety in excellent yields and with nearly perfect enantioselectivities (≥98% ee in most cases). This work marks the first efficient asymmetric construction of optically enriched eight-membered rings via phosphine catalysis
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Direct and Stereospecific [3+2] Synthesis of Pyrrolidines from Simple Unactivated Alkenes ()
Pyrrolidines are central heterocyclic compounds with endless applications in organic synthesis, metal- and organocatalysis. In particular, their potential as ligands for first-row transition-metal catalysts has inspired a new method to access complex poly-heterocyclic pyrrolidines in one-step from available materials. This fundamental step forward is grounded on the discovery of an essential organoaluminum promoter that engages unactivated and electron-rich olefins in intermolecular [3+2] cycloadditions for the first time.
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Targeting the genome stability hub Ctf4 by stapled-peptide design ()
Exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub that links DNA replication, repair and chromosome segregation, represents a novel target for the synthetic lethality approach. Here we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. Screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, sub-micromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4-partner DNA polymerase alpha from the replisome in yeast extracts. Our study provides proof-of-principle evidence for the development of small-molecule inhibitors of the human-CTF4 orthologue AND-1.
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Palladium-Catalyzed Synthesis of Heteroarene-Fused Cyclooctatetraenes via Dehydrogenative Cyclodimerization ()
Arene-fused cyclooctatetraenes (COTs) possess unique structural and electronic properties originated from their saddle-shaped -conjugated architectures. Considerable attention has been paid for the transition-metal-mediated synthesis of these cyclic compounds; however, limited achievements have been represented to date in the efficient construction of heteroarene-fused COTs. In this contribution, we report a novel Pd-catalyzed dehydrogenative cyclodimerization of biheteroarenes via four-fold C-H activation toward the synthesis of a series of heteroarene-fused COTs. A set of mechanistic examinations indicated the involvement of high-valent Pd species prior to the dimerization event in the catalytic cycle. The redox behavior of the obtained COTs is also described briefly.
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Degradable Vanadium Disulfide Nanostructures with Unique Optical and Magnetic Functions for Cancer Theranostics ()
Multifunctional biodegradable inorganic theranostic nano-agents are of great interests to the field of nanomedicine. Herein, VS2 nanosheets upon lipid modification could be converted into ultra-small VS2 nanodots encapsulated inside polyethylene glycol (PEG) modified lipid micelles. Owing to the paramagnetic property, high near-infrared (NIR) absorbance, and chelator-free 99mTc4+ labeling of VS2, such VS2@lipid-PEG nanoparticles could be used for T1-weighted magnetic resonance (MR), photoacoustic (PA),and single photon emission computed tomography (SPECT) tri-modal imaging guided photothermal ablation of tumors. Importantly, along with the gradual degradation of VS2, our VS2@lipid-PEG nanoparticles exhibit effective body excretion without appreciable toxicity. Our work presents the unique advantages of VS2 nanostructures with highly integrated functionalities and biodegradable behaviors, promising for applications in cancer theranostics.
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Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes ()
Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X-ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9. A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the similar interaction patterns to the DprE1-TCA1 complex. Guided by the structures, an optimized molecule was generated with differential inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a clinical candidate to treat TB.
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Wacker-Type Oxidation Using an Iron Catalyst and Ambient Air and Its Application to Late-Stage Oxidation of Complex Molecules ()
We present a practical and general iron-catalyzed Wacker-type oxidation of olefins to ketones which uses ambient air as the sole oxidant. The mild oxidation conditions enable exceptional functional group tolerance, which has not been demonstrated for any other Wacker-type reaction to date. The inexpensive and nontoxic reagents [iron(II) chloride, PMHS (polymethylhydrosiloxane), and air] can, therefore, also be employed to oxidize complex natural-product derived and polyfunctionalized molecules.
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Synthesis of Bicyclo[n.1.0]alkanes via Cobalt-Catalyzed Multiple C(sp3)-H Activation Strategy ()
A cobalt-catalyzed dual C(sp3)-H activation strategy has been developed, providing a novel strategy for the synthesis of bicyclo[4.1.0]heptanes and bicyclo[3.1.0]hexanes. A key to the success of this reaction is the conformation-induced methylene C(sp3)-H activation of the resulting cobaltabicyclo[4.n.1] intermediate. In addition, the synthesis of bicyclo[3.1.0]hexane from pivalamide via triple C(sp3)-H activation has also been demonstrated.
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Synthesis and Characterization of Iridium(V) Coordination Complexes With an N,O-Donor Organic Ligand ()
We have prepared and fully characterized two isomers of [IrIV(dpyp)2] (dpyp = meso-2,4-di(2-pyridynyl)-2,4-pentanediolate). These complexes can be cleanly oxidized to [IrV(dpyp)2]+, which to our knowledge represent the first coordination complexes of Ir(V) in an N,O-donor environment. One isomer has been fully characterized in the Ir(V) state, including by x-ray crystallography, XPS, and DFT calculations, all of which support metal-centered oxidation. The unprecedented stability of these Ir(V) complexes is ascribed to the exceptional donor strength of the ligands, their resistance to oxidative degradation, and the presence of four highly donor alkoxide groups in a plane, which breaks the degeneracy of the d-orbitals and favors oxidation.
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A semi-synthetic glycoconjugate vaccine candidate for carbapenem-resistant Klebsiella pneumoniae ()
Hospital acquired infections are an increasingly serious health concern. Infections caused by carpabenem-resistant Klebsiella pneumoniae (CR-Kp) are especially problematic, with a 50% average survival rate. CR-Kp are isolated from patients with ever greater frequency: 7% within the EU but 62% in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Here, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross-reactive antibodies against CR-Kp CPS in mice and rabbits. Whole cell ELISA was used to establish the surface staining of CR-Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi-synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium.
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Compartmentalizing supramolecular hydrogels using aqueous multi-phase systems ()
We present a generic method for compartmentalization of supramolecular hydrogels by using water-in-water emulsions based on aqueous multi-phase systems (AMPS). By forming the low-molecular-weight hydrogel throughout all phases of all-aqueous emulsions, we created distinct, micro-compartmentalized materials. This structuring approach offers control over the composition of each type of the compartments by directing the partitioning of objects to be encapsulated. Moreover, our method allows for barrier-less, dynamic exchange of even large hydrophilic solutes (MW ~ 60 kDa) between separate aqueous compartments. We expect these features to find use in the fields of, for instance, micro-structured catalysts, templating, and tissue engineering.
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Reagent-Free C-H/N-H Cross-Coupling: Regioselective Synthesis of N-Heteroaromatics from Biaryl Aldehydes and NH₃ ()
An unprecedented synthesis of N-heteroaromatics from biaryl aldehydes and NH3 through reagent-free C-H/N-H cross-coupling has been developed. The electrosynthesis uses NH3 as an inexpensive and atom-economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N-heteroaromatic products.
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C-H Bond Trifluoromethylation of Arenes Enabled by a Robust, High-Valent NiIV-Complex. ()
The robust, high-valent NiIV complex [(Py)2NiIVF2(CF3)2] 3, is reported. The structure of 3 was fully characterized by NMR, XRD and EA. 3 reacts with aromatics at 25°C to form the corresponding benzotrifluorides in nearly quantitative yield. Monomeric and dimeric NiIIICF3 complexes 2.Py and 2 were identified as key intermediates, and their structures were unambiguously assigned by EPR and XRD analysis. Preliminary kinetic study coupled to experimental isolation of reaction intermediates proves that the C-H bond breaking/C-CF3 bond forming sequence can occur both with the NiIVCF3 and NiIIICF3 centers.
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In situ Investigation of Methane Dry Reforming on M-CeO2(111) {M= Co, Ni, Cu} Surfaces: Metal-Support Interactions and the activation of C-H bonds at Low Temperature ()
Studies with a series of M-CeO2(111) {M= Co, Ni, Cu} surfaces indicate that metal-oxide interactions can play a very important role for the activation of methane and its reforming with CO2 at relatively low temperatures (600-700 K). Among the systems examined, Co-CeO2(111) exhibits the best performance and Cu-CeO2(111) has negligible activity. Experiments using ambient pressure XPS indicate that methane dissociates on Co-CeO2(111), at temperatures as low as 300 K, generating CHx and COx species on the catalyst surface. The results of density-functional calculations show a reduction in the methane activation barrier from 1.07 eV on Co(0001) to 0.87 eV on Co2+/CeO2(111), and to only 0.05 eV on Co0/CeO2-x(111). At 700 K, under methane dry reforming conditions, CO2 dissociates on the oxide surface and a catalytic cycle is established without coke deposition. A significant part of the CHx formed on the Co0/CeO2-x (111) catalyst recombines to yield ethane or ethylene.
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Hydrogen Isotope Exchange - The Foundation of C-H activation and Isotope Science in Drug Discovery ()
The wide range of applications involving hydrogen isotopes in drug discovery and beyond dictates that their selective and efficient installation continues to present an important and continuing challenge to synthetic chemists. In this review advances in the field of hydrogen isotope exchange over the last ten years and related hydrogen isotope applications in a broad spectrum of disciplinary areas are brought together.
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Solvation Accounts for the Counter-Intuitive Nucleophilicity Ordering of Peroxide Anions ()
The nucleophilic reactivities (N, sN) of peroxide anions (generated from aromatic and aliphatic peroxyacids or alkyl hydroperoxides) were investigated by following the kinetics of their reactions with a series of benzhydrylium ions (Ar2CH+) in alkaline aqueous solutions at 20 °C. The second-order rate constants revealed that deprotonated peroxyacids (RCO3-), though being the considerably weaker Brønsted bases, react much faster than anions of aliphatic hydroperoxides (ROO-). Substitution of the rate constants of their reactions with benzhydrylium ions into the linear free energy relationship lg k = sN(N + E) furnished nucleophilicity parameters (N, sN) of peroxide anions, which were successfully applied to predict the rates of Weitz-Scheffer epoxidations. DFT calculations with inclusion of solvent effects by means of the Integral Equation Formalism (IFM) version of the Polarizable Continuum Model (PCM) were performed to rationalize the observed reactivities.
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A Synthesis of Crocagin A ()
Crocagin A (1) combines an attractive molecular structure with an unusual biosynthesis and bioactivity. Here, we present an efficient synthesis of crocagin A that hinges on an early formation of its heterotricyclic core, an electrophilic amination, and a stereoselective hydrogenation of a tetrasubstituted double bond. Our synthesis confirms the absolute configuration of crocagin A and provides access to the natural product and derivatives thereof for further biological testing.
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Acid Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release ()
Stimuli responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. Here, we report a new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers, which can degrade and release the encapsulated cargo with accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition property of CB[n] type hosts. Cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH.
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Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-targeted Bioactive Ligands ()
While myriad non-coding RNAs are known to be essential in cellular processes and misregulated in diseases, the development of RNA-targeted small molecule probes has met with limited success. To elucidate guiding principles for selective small molecule:RNA recognition, we analyzed cheminformatic and shape-based descriptors for 104 RNA-targeted ligands with demonstrated biological activity (RNA-targeted BIoactive ligaNd Database, RBIND). We then compared R-BIND to both FDA-approved small molecule drugs and RNA ligands without reported bioactivity. Several striking trends emerged for bioactive RNA ligands, including: i) compliance to medicinal chemistry rules; ii) distinctive structural features; and iii) enrichment in "rod-like" over other shapes. This work provides unique insights that directly facilitate the selection and synthesis of RNA-targeted libraries with the goal of efficiently identifying selective small molecule ligands for therapeutically relevant RNAs.
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Quasi-Dual-Packed-Kernelled Au49(2,4-DMBT)27 Nanoclusters and the Influence of Kernel Packing on the Electrochemical Gap ()
Although face-centered cubic (fcc), body-centered cubic (bcc), hexagonal close-packed (hcp) and other structured gold nanoclusters have been reported, it is still unclear if gold nanoclusters with mix-packed (e.g., fcc and non-fcc) kernels exist, and the correlation between kernel packing and the properties of gold nanoclusters is unknown. Herein, a novel Au49(2,4-DMBT)27 nanocluster with shell electron count of 22 has been synthesized and structurally resolved by single-crystal X-ray crystallography, which revealed that Au49(2,4-DMBT)27 contained a unique Au34 kernel consisting of one quasi-fcc-structured Au21 and one non-fcc-structured Au13 unit (where 2,4-DMBTH = 2,4-dimethylbenzenethiol). Such a quasi-dual-packed structure has not been previously reported. Interestingly, further experiments revealed that the kernel packing greatly influenced the electrochemical gap (EG) and that the fcc structure possessed a larger EG than the investigated non-fcc structure.
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Real-Time Intracellular Measurements of ROS and RNS in Living Cells with Single Core-Shell Nanowire Electrodes ()
Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living cell level in real time. Cylindrical nanowires electrodes (NWEs) required for intracellular measurements create a great challenge for keeping excellent electrochemical and mechanical performances. Herein, we disclose a facile and robust solution to this problem based on a SiC-core-shell unique design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano-core and excellent electrochemical performances brought by the ultrathin carbon shell that can be used as such or platinized. The biological interest of such NWEs is illustrated by the first time quantitative measurement of ROS/RNS in individual phagolysosomes of living macrophages. Since the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to track quantitatively biological functions occurring inside cells and their organelles.
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Palladium-Catalysed Carbon-Fluorine and Carbon-Hydrogen Bond Alumination of Fluoroarenes and Heteroarenes ()
Through serendipitous discovery, a palladium bis(phosphine) complex was identified as a catalyst for the selective transformation of sp2C-F and sp2C-H bonds of fluoroarenes and heteroarenes to sp2C-Al bonds (19 examples, 1 mol% Pd loading). The carbon-fluorine bond functionalization reaction is highly selective for the formation of organoaluminum products in preference to hydrodefluorination products (selectivity = 4.4:1 to 27:1). Evidence is presented for a two step mechanism in which hydrodefluorination is followed by sp2C-H alumination.
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Redox-Neutral Manganese(I)-Catalyzed C-H Activation: Traceless Directing Group Enabled Regioselective Annulation ()
An unprecedented strategy using traceless directing groups (TDG) to promote the redox-neutral Mn(I)-catalyzed regioselective synthesis of N-heterocycles is reported. Alkyne coupling partners bearing traceless directing group, which serve as both chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, featuring switchable regioselectivity, simple conditions, and gram-scale synthesis. The application of this strategy in the concise synthesis of bioactive compound PK11209 and pharmaceutical moxaverine is also described.
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Donor-Acceptor Complex Enables Alkoxyl Radical Generation for Metal-Free C(sp3)-C(sp3) Cleavage and Allylation/Alkenylation ()
The alkoxyl radical is an essential and prevalent reactive intermediate for chemical and biological studies. Here we report the first donor-acceptor complex-enabled alkoxyl radical generation under metal-free reaction conditions induced by visible light. Hantzsch ester forms the key donor-acceptor complex with N-alkoxyl derivatives, which is elucidated by a series of spectrometry and mechanistic experiments. Selective C(sp3)-C(sp3) bond cleavage and allylation/alkenylation is demonstrated for the first time using this photocatalyst-free approach with linear primary, secondary, and tertiary alkoxyl radicals.
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Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross-Coupling of Amide Derivatives ()
Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold particular significance. A conventional method for the synthesis of C-P bonds involves cross-coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The reaction constitutes the first example of a transition-metal-catalyzed generation of C-P bonds from amides. This redox-neutral protocol can be combined with site-selective conventional cross-coupling. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni-catalyzed C-P bond forming method will find broad application.
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Fe Doped Ni3C nanodots in N-doped carbon nanosheets for efficient hydrogen-evolution and oxygen-evolution electrocatalyst ()
Uniform Ni3C nanodots dispersed in ultrathin N-doped carbon nanosheets were successfully prepared by carburization of the two dimensional (2D) nickel-cyanide coordination polymer precursors. The Ni3C based nanosheets have lateral length of about 200 nm and thickness of 10 nm. When doped with Fe, the Ni3C based nanosheets exhibited outstanding electrocatalytic properties for both hydrogen evolution reactions (HER) and oxygen evolution reactions (OER). For example, 2 at% Fe (atomic percent) doped Ni3C nanosheets depict a low overpotential (292 mV) and a small Tafel slope (41.3 mV dec-1) for HER in KOH solution. An outstanding OER catalytic property is also achieved with a low overpotential of 275 mV and a small Tafel slope of 62 mV dec-1 in KOH solution. Such nanodots incorporated 2D hybrid structures can serve as an efficient bifunctional electrocatalyst for overall water splitting.
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Flavylium polymethine fluorophores for imaging in the near- and shortwave infrared ()
Bright fluorophores in the near infrared and shortwave infrared (SWIR) are essential for optical imaging in vivo. Herein, we utilize a 7-dimethylamino flavylium heterocycle to construct a panel of novel red-shifted polymethine dyes, with emission from 680 to 1045 nm. Photophysical characterization reveals that the 1- and 3-methine dyes display enhanced photostabilities and the 5- and 7-methine dyes exhibit exceptional brightness for their respective spectral regions. A micelle formulation of the 7-methine facilitates SWIR imaging in mice. This report represents the first polymethine dye designed and synthesized for in vivo imaging in the SWIR.
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DNA Trojan Horses: The Self-Assembled Floxuridine-Containing DNA Polyhedra for Cancer Therapy ()
Based on the structural similarity, herein, nucleoside analogue therapeutics were integrated into DNA strands through conventional solid-phase synthesis. By elaborately designing their sequences, floxuridine-integrated DNA strands were synthesized and self-assembled into well-defined DNA polyhedra with definite drug loading ratio as well as tunable size and morphology. As a novel drug delivery system, these drug-containing DNA polyhedra could ideally mimic the Trojan Horse to deliver chemotherapeutics into tumor cells and fight against cancer. Both in vitro and in vivo results demonstrate that DNA Trojan Horse with buckyball architecture exhibits superior anticancer capability over the free drug and other formulations. With precise control over drug loading ratio and structure of the nanocarriers, DNA Trojan Horse may play an important role in anticancer treatment and exhibit great potential in translational nanomedicine.
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Self-Cleaning Catalyst Electrodes for Stabilized CO2 Reduction to Hydrocarbons ()
Cu metal catalysts have received substantial attention due to their distinct capabilities to catalyze CO2 electroreduction to hydrocarbons. However, they suffer from fast deactivation. Developing a Cu electrocatalyst with long-term catalytic durability for CO2 reduction remains a big challenge. Here we report a surface-restructuring strategy for realizing self-cleaning Cu catalyst electrodes with unprecedented catalytic stability toward CO2 reduction. Under the working conditions, the Pd atoms pre-deposited on Cu surface induce continuous morphological and compositional restructuring of the Cu, which constantly refreshes the catalyst surface and thus maintains the catalytic properties for CO2 reduction to hydrocarbons. Our Pd-decorated Cu electrode can catalyze CO2 reduction with relatively stable selectivity and current density for up to 16 h, representing one of the best catalytic durability performances among all Cu electrocatalysts for effective CO2 con-version to hydrocarbons.
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Molecular-recognition mediated transformation of single-chain polymer nanoparticles into crosslinked polymer films ()
We describe single-chain polymer nanoparticles (SCNPs) possessing intramolecular dynamic covalent crosslinks that can transform into polymer films through a molecular recognition-mediated crosslinking process. The SCNPs utilize molecular recognition with surface-immobilized proteins to concentrate themselves upon a substrate, bringing the SCNPs into close spatial proximity with one another and allowing their dynamic covalent crosslinkers to undergo intra-to interpolymer chain crosslinking leading to the formation of polymeric film. This new approach to polymer film formation presents a potential method to 'wrap' surfaces displaying molecular recognition motifs—which could potentially include viral, cellular and bacterial surfaces or designed artificial surfaces displaying multivalent recognition motifs—within a layer of polymer film.
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Two-Dimensional Physical Gels Can Exist even at Zero Surface Pressure at the Air/Water Interface - Rheology of Self-Assembled Domains of Small Molecules ()
Films of mesoscopic domains self-assembled from fluorocarbon/hydrocarbon diblocks (FnHm) at the air/water interface were found to display highly elastic behavior. We determined the interfacial viscoelasticity of domain-patterned FnHm Langmuir monolayers by applying periodic shear stresses. Remarkably, we found the formation of two-dimensional gels even at zero surface pressure. These monolayers are predominantly elastic, which is unprecedented for surfactants, exhibiting gelation only at high surface pressures. Systematic variation of the hydrocarbon (n = 8; m = 14, 16, 18, 20) and fluorocarbon (n = 8, 10, 12; m = 16) block lengths demonstrated that subtle changes in the block length ratio significantly alter the mechanics of two-dimensional gels across one order of magnitude. These findings open perspectives for the fabrication of two-dimensional gels with tuneable viscoelasticity via self-assembly of mesoscale, low molecular weight materials.
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Visible Light-Mediated Selective Arylation of Cysteine in Batch and Flow ()
A mild visible light-mediated strategy for cysteine arylation is presented. The method relies on the use of Eosin Y as a metal-free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine-containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, PBS buffer) within a short reaction time.
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Scalable dry-production of superior 3D net-like FeOx/C composite anode material for lithium ion battery ()
Carbon-based transition metal oxides are considered as an appropriate anode material candidate for lithium ion batteries. Herein, a simple and scalable dry-production method is developed to produce carbon-encapsulated 3D net-like FeOx/C material. The process simply associates with pyrolysis of solid carbon source of filter paper with adsorbed ferrite nitrate. The carbon derived from filter paper induces a carbothermal reduction to form metallic Fe, the adding carbon and metal Fe increase the conductivity of this material. As expected, this 3D net-like FeOx/C composite delivers excellent charge capacity of 851.3 mAh g-1 after 50 cycles at 0.2 A g-1 as well as high stability and rate performance of 714.7 mAh g-1 after 300 cycles at 1 A g-1. Superior performance, innocuity, low-cost, and high yield may greatly stimulate the practical application of the products as anode materials in lithium ion batteries.
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Nickel-Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Access Indolines ()
A nickel-catalyzed asymmetric reductive Heck reaction of aryl chlorides affords substituted indolines in high enantioselectivity. Manganese powder was used as the terminal reductant and water as proton source.
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Gold-catalyzed [4+2]-Annulation/Cyclization Cascades of Benzisoxazoles with Propiolate Derivatives to Access Highly Oxygenated Tetrahydroquinolines ()
This work describes gold-catalyzed annulations of electron-deficient alkynes with benzisoxazoles to yield quinoline oxides chemoselectively. Chemical functionalizations of these resulting azacyclic compounds afforded various oxygenated tetrahydroquinolines that are present as the cores of many bioactive molecules. With the same reactants, a new relay catalysis using gold and Zn(II) catalysts affords highly oxygenated tetrahydroquinoline derivatives stereoselectively.
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Nanoscale Metal-Organic Layers for Deeply Penetrating X-ray Induced Photodynamic Therapy ()
We report the rational design of metal-organic layers (MOLs) that are built from [Hf6O4(OH)4(HCO2)6] secondary building units (SBUs) and Ir[bpy(ppy)2]+- or Ru(bpy)32+-derived tricarboxylate ligands (Hf-BPY-Ir or Hf-BPY-Ru; bpy = 2,2'-bipyridine, ppy = 2-phenyl-pyridine) and their applications in deeply penetrating X-ray induced photodynamic therapy (X-PDT) of colon cancer. Heavy Hf atoms in the SBUs efficiently absorb X-rays and transfer energy to Ir[bpy(ppy)2]+ or Ru(bpy)32+ moieties to induce PDT by generating reactive oxygen species (ROS). The ability of X-rays to penetrate deeply into tissue and efficient ROS diffusion through ultrathin 2-D MOLs (~1.2 nm) enable highly effective X-PDT to afford superb anticancer efficacy.
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Divergent Asymmetric Total Synthesis of Mulinane Diterpenoids ()
We have achieved the first concise, divergent, asymmetric total syntheses of mulinane diterpenoids. Specifically, we developed a new strategy featuring a key intramolecular Friedel-Crafts reaction to construct the chiral fused 5-6-6 tricyclic motif, followed by sequential Birch reduction, conjugate methylation, and homologation/ring-expansion reactions to furnish the desired 5-6-7 tricyclic skeleton bearing five contiguous stereocenters. With this efficient strategy, seven mulinane diterpenoids and two analogues were synthesized via late-stage functional modification or functionalization in 8.6-20% overall yields and 11-15 steps
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Conformationally Flexible Bis(9-fluorenylidene)porphyrin Diradicaloids ()
A stable 5,10-bis(9-fluorenylidene)porphyrin (Por-Fl) diradicaloid was synthesized. It shows a quinoidal, saddle-shaped geometry in single crystal but can be thermally populated to triplet diradical both in solution and in solid state. Coordination with Ni2+ ion (Por-Fl-Ni) does not significantly change the contorted conformation but reduces the singlet-triplet gap. Heat-induced geometric change can explain the observed paramagnetic properties as well as unusual hysteresis in SQUID measurements. On the other hand, protonation (Por-Fl-2H+) dramatically changes the conformation while maintains the closed-shell electronic structure. Our studies demonstrate how heat, coordination and protonation affect the geometry, diradical character and physical properties of conformationally flexible open-shell singlet diradicaloids.
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The Charge Transfer Approach to Heavier Main-Group Element Radicals in Transition Metal Complexes ()
The phosphorus radical coordinated CoII and FeII complexes 1Co and 1Fe were facilely obtained through the charge transfer approach from the MI precursors LMI(tol) (M = Co, Fe; L = CH(MeC=NDipp)2, Dipp = 2,6-iPr2C6H3) to the diazofluorenylidene-substituted phosphaalkene 1. Structural, magnetic and computational studies on 1Co and 1Fe indicate a weak antiferromagnetic interaction between the high-spin MII ion and the phosphorus radical, resulting in a triplet and quartet ground state, respectively. Complexes 1Co and 1Fe represent the first examples of phosphorus radical coordinated transition metal complexes synthesized via charge transfer, providing a new approach to access radicals of heavier main-group elements.
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Rapid Access to Nanographenes and Fused Heteroaromatics by Palladium-Catalyzed Annulative π-Extension Reaction of Unfunctionalized Aromatics with Diiodobiaryls ()
Efficient and rapid access to nanographenes and π-extended fused heteroaromatics is important in materials science. Here we report a Pd-catalyzed efficient one-step annulative π-extension (APEX) reaction of PAHs and heteroaromatics, producing various π-extended aromatics. In the presence of a cationic Pd complex, triflic acid, silver pivalate, and diiodobiaryls, diverse unfunctionalized PAHs and heteroaromatics were directly transformed into larger PAHs, nanographenes, and π-extended fused heteroaromatics in a single step. In the reactions affording [5]helicene substructures, simultaneous dehydrogenative ring closures occur at the fjord regions to form unprecedented larger nanographenes. This successive APEX reaction is notable as it stiches five aryl-aryl bonds by C-H functionalization in a single operation. Moreover, the unique molecular structures, crystal-packing structures, photophysical properties, and frontier molecular orbitals of the thus-formed nanographenes were elucidated.
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Remote meta-C−H cyanation of arenes enabled by pyrimidine-based auxiliary ()
An easily removable pyrimidine-based auxiliary has been employed for the remote meta-C−H cyanation of arenes. The scope of this Pd-catalyzed cyanation reaction using copper(I) cyanide as the cyanating agent has been demonstrated with benzylsilanes, benzylsulfonates, benzylphophonates, phenethylsulfonates and phenethyl ether derivatives. Present protocol was utilized for the synthesis of pharmaceutically valuable precursors.
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Selective α-Oxyamination and Hydroxylation of Aliphatic Amides ()
Compared to the α-functionalization of aldehydes, ketones, even esters, the direct α-modification of amides is still a big challenge because of the lowest α-CH acidity among all carbonyl chemicals. Most challengingly, α-functionalization of N-H (primary and secondary) amides simultaneous containing the unactived α-C-H bond and a competitively active N-H bond, remains elusive. A general and efficient oxidative α-oxyamination and hydroxylation of aliphatic amides including secondary N-H amides was discribed. This transition-metal-free chemistry with high chemoselectivity provides an efficient approach to α-hydroxyl amides, which are significant scaffolds in pharmaceuticals and materials. This oxidative protocol significantly enables the selective functionalization of inert α-C-H bond with the complete preservation of active N-H bond.
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Highly Selective Palladium-Catalyzed Allenic C-H Bond Oxidation for Synthesis of [3]Dendralenes ()
A highly selective palladium-catalyzed allenic C-H bond oxidation was developed, which provides a novel and straightforward synthesis of [3]dendralene derivatives. A variety of [3]dendralenes with diverse substitution patterns are accessible with good efficiency and high stereoselectivity. The reaction tolerates a broad substrate scope containing various functional groups on the allene moiety, including ketone, aldehyde, ester and phenyl groups. Also, a wide range of olefins with both electron-donating and electron-withdrawing aryls, acrylate, sulfone and phosphonate groups are tolerated.
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Helix to Super-Helix Transition in π-Systems Self-assembly: Superseding of Molecular Chirality at Hierarchical Level ()
Higher-order super-helical structures derived from biological molecules are known to evolve through opposite coiling of the initial helical fibers as seen in the case of collagen protein. Herein we describe a similar kind of phenomenon in a π-system self-assembly of chiral OPE derivatives (S)-1 and (R)-1 which explains the unequal formation of both left- and right-handed helices from molecule having a specific chiral center. The concentration and temperature-dependent circular dichroism (CD) and UV-Vis spectroscopic studies revealed that the initial formation of helical aggregates is in accordance with the molecular chirality. However, at the next level of hierarchical self-assembly, coiling of the fibers occurs with opposite handedness, thereby superseding the command of the molecular chirality. This has been confirmed with the help of solvent-dependent decoiling of super-helical structures and concentration-dependent morphological analysis.
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Cooperative Supramolecular Polymerization of Fluorescent Platinum Acetylides for Optical Waveguide Applications ()
One-dimensional organic structures with well-oriented π-aggregation, strong emission, and ease of processability are desirable for optoelectronic waveguiding devices. Herein, we have developed an unprecedented strategy to attain this objective, by self-assembling platinum(II) acetylides into fluorescent supramolecular polymers via cooperative mechanism. The resulting high-molecular-weight supramolecular polymers are capable of forming electrospun microfibers with uniform geometry and smooth surface, which enable light propagation with extremely low scattering loss (0.008 dB μm-1). With the elaborate combination of bottom-up supramolecular polymerization and top-down electrospinning techniques, this work offers a novel and versatile avenue toward high-performance optical waveguiding materials.
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Bridging Dealumination and Desilication for the Synthesis of Hierarchical MFI Zeolites ()
Rational design of zeolite-based catalysts calls for flexible tailoring of porosity and acidity beyond micropore dimension. To date, dealumination has been applied extensively as an industrial technology for the tailoring of zeolite in micropore dimension, whereas desilication has separately shown its potentials in the creation of mesoporosities. The free coupling of dealumination with desilication will bridge the tailoring at micro/mesopore dimensions; however, such coupling has been prevailingly confirmed as an impossible mission. In this work, a consecutive dealumination-desilication protocol unprecedentedly enables the introduction of uniform intracrystalline mesopores (4-6 nm) into the microporous Al-rich zeolites. The decisive impacts of steaming step have been firstly discovered. These findings revitalize the functions of dealumination in porosity tailoring, and stimulate the pursuit of new tool-boxes for the tailoring of industrially relevant Al-rich zeolites.
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New experimental reference data for hexafluorinated propanol by exploring an unusual intermolecular torsional balance ()
The hydrogen-bonded dimer of 1,1,1,3,3,3-hexafluoro-2-propanol forms an intermolecular -OH...O- torsional balance, in which the acceptor OH group can point away from or towards the fluorines of the donor. It prefers the former arrangement in the free dimer, but dinitrogen coordination of the acceptor OH favors the latter, as FTIR spectroscopy in supersonic jets suggests. A multi-step divide-and-conquer strategy was employed to rule out density functional and other inexpensive quantum chemical methods within the harmonic approximation. Among 20 exploratory single-determinant computational approaches, only the ones based on the B3LYP-D3 functional provide a satisfactory description of six carefully assessed experimental constraints for this fluorous hydrogen bond competition. Low barrier intermolecular torsion balances are proposed more generally as non-covalent conformational energy benchmarking tools.
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Divergent CH Annulation for Multi-Fused N-Heterocycles: Regio- and Stereospecific Cyclizations of N-Alkynylindoles ()
N-Alkynylindoles were divergently cyclized for the synthesis of multi-fused N-heterocycles. An ortho-aryl palladium species was added to the -position of an ynamine to generate (Z)-6-alkylidene/benzylidene-6H-isoindolo[2,1-a]indoles, while Pt-catalyzed -addition via -activation gave 5-alkyl/arylindolo[2,1-a]isoquinolines. Double cyclizations using PdCl2 and oxidant afforded bright yellow benzo[7,8]indolizino[2,3,4,5-ija]quinolines, the synthesis of which was also demonstrated in a different synthetic route.
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Steering Surface Reaction Dynamics with Self-Assembly Strategy ()
Ullmann coupling of 4-bromobiphenyl thermally catalyzed on Ag(111), Cu(111) and Cu(100) surfaces was scrutinized by scanning tunneling microscopy as well as theoretical calculations. Detailed experimental evidence showed that whether the initially formed organometallic intermediate self-assembled or sparsely dispersed at surfaces essentially determined its subsequent reaction pathways. In specific, the assembled organometallic intermediates at full coverage underwent a single-barrier process to directly convert into the final coupling products while the sparsely dispersed ones at low coverage went through a double-barrier process via newly identified clover-shaped intermediates prior to their formation of the final coupling products. This demonstrates that the self-assembly strategy can efficiently steer surface reaction pathways and dynamics.
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Jubilee Issue 150 Years of the GDCh ()
Berlin was just a large village in 1867 at least in the eyes of August Wilhelm von Hofmann, but nevertheless, it had such an intellectually stimulating atmosphere that he left London and returned to Berlin. He promptly threw himself into his many functions, including organizing the chemists in Berlin and “the whole of Germany” at a time when Germany was finally on the verge of becoming a united country. The rise and fall of the Deutsche Chemische Gesellschaft (DChG; German Society of Chemistry) is recounted by J. A. Johnson in his Review ((DOI: 10.1002/anie.201702487). In 1945 the DChG was morally and organizationally in ruins, and it was not until 1949 that the Gesellschaft Deutscher Chemiker (GDCh; German Chemical Society) was formed: It was built upon the positive early history of the DChG, and is therefore now, in 2017, celebrating a 150 year jubilee. The highlights of the GDCh′s celebrations are a ceremony in Berlin on September 10th and the Angewandte Fest Symposium the following day. Many of the speakers, as well as members of the Editorial and International Advisory Boards, have articles in this Special Issue. Green is the GDCh′s color and green is also the color of hope. I trust that chemists in the future will contribute even more to the benefit of humanity and our planet than they have done in the past. To help turn this hope into a reality is an aim of the GDCh′s jubilee events in Berlin and of this Special Issue.
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Controlled Supramolecular Self-Assembly of Super-charged β-Lactoglobulin A–PEG Conjugates into Nanocapsules ()
The synthesis and characterization of a new protein–polymer conjugate composed of β lactoglobulin A (βLG A) and poly(ethylene glycol) PEG is described. βLG A was selectively modified to self-assemble by super-charging via amination or succinylation followed by conjugation with PEG. An equimolar mixture of the oppositely charged protein–polymer conjugates self-assemble into spherical capsules of 80–100 nm in diameter. The self-assembly proceeds by taking simultaneous advantage of the amphiphilicity and polyelectrolyte nature of the protein–polymer conjugate. These protein–polymer capsules or proteinosomes are reminiscent of protein capsids, and are capable of encapsulating solutes in their interior. We envisage this approach to be applicable to other globular proteins. Super-charged self-assembly: The protein β lactoglobulin A (βLG A) was selectively modified to self-assemble by amination or succinylation followed by conjugation with poly(ethylene glycol) PEG. An equimolar mixture of the oppositely charged protein–polymer conjugates self-assemble into spherical capsules of 80–100 nm in diameter.
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Unified Total Synthesis of Polyoxin J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions ()
Polyoxins J (1 a) and L (1 b) are important nucleoside antibiotics. The complex and densely functionalized dipeptide structures of 1 a and 1 b contain thymine and uracil nucleobases, respectively. Herein we report the unified total synthesis of 1 a, 1 b, and their artificial analogues 1 c and 1 d with trifluorothymine and fluorouracil structures. Decarbonylative radical coupling between α-alkoxyacyl tellurides and a chiral glyoxylic oxime ether led to chemo- and stereoselective construction of the ribonucleoside α-amino acid structures of 1 a–d without damaging the preinstalled nucleobases. The high applicability of the radical-based methodology was further demonstrated by preparation of the trihydroxynorvaline moiety of 1 a–d. The two amino acid fragments were connected and elaborated into 1 a–d (longest linear sequence: 11 steps). Compounds 1 a and 1 b assembled in this way exhibited potent activity against true fungi, while only 1 d was active against Gram-positive bacteria. On the double: The important nucleoside antibiotics polyoxins J and L were synthesized along with two fluorinated analogues by a newly developed radical-based strategy that enabled rapid assembly of the four polyoxins in a unified fashion. Preliminary biological evaluation show the distinct antimicrobial spectra of the synthesized polyoxins.
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Takahiro Nishimura ()

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Tomoya Miura ()

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Nickel-Catalyzed Enantioselective Conjunctive Cross-Coupling of 9-BBN Borates ()
Catalytic enantioselective conjunctive cross-coupling between 9-BBN borate complexes and aryl electrophiles can be accomplished with Ni salts in the presence of a chiral diamine ligand. The reactions furnish chiral 9-BBN derivatives in an enantioselective fashion and these are converted to chiral alcohols and amines, or engaged in other stereospecific C−C bond forming reactions. Conjunctive coupling: Ni-Catalyzed conjunctive couplings furnish chiral 9-BBN derivatives in an enantioselective fashion and these are converted to chiral alcohols and amines, or they can be engaged in other stereospecific C−C bond forming reactions.
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Paolo Samorì ()

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Reductive Decarboxylative Alkynylation of N-Hydroxyphthalimide Esters with Bromoalkynes ()
A new method for the synthesis of terminal and internal alkynes from the nickel-catalyzed decarboxylative coupling of N-hydroxyphthalimide esters and bromoalkynes is presented. This reductive cross-electrophile coupling is the first to use a C(sp)−X electrophile, and appears to proceed via an alkynylnickel intermediate. The internal alkyne products are obtained in yields of 41–95 % without the need for a photocatalyst, light, or a strong oxidant. The reaction displays a broad scope of carboxylic acid and alkyne coupling partners, and can tolerate an array of functional groups, including carbamate NH, halogen, nitrile, olefin, ketone, and ester moieties. Mechanistic studies suggest that this process does not involve an alkynylmanganese reagent and instead proceeds through nickel-mediated bond formation. Terminal and internal alkynes can be synthesized by a nickel-catalyzed decarboxylative coupling of N-hydroxyphthalimide esters and bromoalkynes. The reaction displays a broad scope of carboxylic acid and alkyne coupling partners, and tolerates an array of functional groups, including carbamate, halogen, nitrile, olefin, ketone, and ester moieties.
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How Understanding the Role of an Additive Can Lead to an Improved Synthetic Protocol without an Additive: Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes ()
The use of additives for organic synthesis has become a common tactic to improve the outcome of organic reactions. Herein, by using an organocatalytic process for the synthesis of chiral diarylmethyl alkynes as a platform, we describe how an additive is involved in the improvement of the process. The evolution of an excellent synthetic protocol has been achieved in three stages, from 1) initially no catalyst turnover, to 2) good conversion and enantioselectivity with a superior additive, and eventually 3) even better efficiency and selectivity without an additive. This study is an important and rare demonstration that understanding the role of additive can be so beneficial as to obviate the need for the additive. Addition and subtraction: On the basis of an organocatalytic process, it is shown how a reaction can be evolved from an initial stage without catalyst turnover to a highly efficient and enantioselective transformation in the presence of an additive, and eventually without the additive (see picture). Thus, by understanding the role of an additive, it was possible to redesign and significantly improve the synthetic protocol.
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Enzymatic Synthesis of Homogeneous Chondroitin Sulfate Oligosaccharides ()
Chondroitin sulfate (CS) is a sulfated polysaccharide that plays essential physiological roles. Here, we report an enzyme-based method for the synthesis of a library of 15 different CS oligosaccharides. This library covers 4-O-sulfated and 6-O-sulfated oligosaccharides ranging from trisaccharides to nonasaccharides. We also describe the synthesis of unnatural 6-O-sulfated CS pentasaccharides containing either a 6-O-sulfo-2-azidogalactosamine or a 6-O-sulfogalactosamine residue. The availability of structurally defined CS oligosaccharides offers a novel approach to investigate the biological functions of CS. In large numbers: An enzyme-based method enabled the synthesis of 15 chondroitin sulfate (CS) oligosaccharides. This library covers 4-O- and 6-O-sulfated oligosaccharides ranging from trisaccharides to nonasaccharides. Unnatural 6-O-sulfated CS pentasaccharides containing either a 6-O-sulfo-2-azidogalactosamine or a 6-O-sulfogalactosamine residue were also synthesized.
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A 2-O-Methylriboside Unknown Outside the RNA World Contains Arsenic ()
Lipid-soluble arsenic compounds, also called arsenolipids, are ubiquitous marine natural products of currently unknown origin and function. In our search for clues about the possible biological roles of these compounds, we investigated arsenic metabolism in the unicellular green alga Dunaliella tertiolecta, and discovered an arsenolipid fundamentally different from all those previously identified; namely, a phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside. The discovery is of particular interest because 2-O-methylribosides have, until now, only been found in RNA. We briefly discuss the significance of the new lipid in biosynthesis and arsenic biogeochemical cycling. A little stranger: Studies of the arsenic metabolism in the unicellular green alga Dunaliella tertiolecta revealed an arsenolipid fundamentally different from all those previously identified, namely, a phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside (see picture). The discovery is of particular interest because 2-O-methylribosides have, until now, only been found in RNA.
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Pristine DNA Hydrogels from Biotechnologically Derived Plasmid DNA ()
DNA hydrogels are of great interest for a variety of biomedical applications owing to their biocompatibility and biodegradability but the advantages of DNA hydrogels have not been exploited yet because of their limited availability. Thus far, DNA hydrogels have been prepared from synthetically derived building blocks, and their production on large scale would be far too expensive. As an alternative, here the generation of DNA hydrogels from plasmid DNA is reported. Plasmid DNA can be prepared on large scale at reasonable costs by a fermentation process. The desired linear DNA building blocks are then obtained from the plasmid DNA by enzymatic digestion. Gel formation is carried out by covalent bond formation between individual building blocks via enzymatic ligation. The generation of pristine DNA hydrogels from plasmid DNA is thus presented for the first time. The viscoelastic properties of the hydrogels were studied by rheology, which confirmed that the gels have storage moduli G′ of >100 Pa. (De)construction: Pristine DNA hydrogels were formed from biotechnologically derived plasmid DNA through ligation of longer or shorter fragments, obviating the need for DNA building blocks prepared by solid-phase synthesis. The rheological properties of the hydrogels can be adjusted by varying the length and sequence of the employed fragments as well as the experimental conditions.
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Fractal MTW Zeolite Crystals: Hidden Dimensions in Nanoporous Materials ()
Screw dislocation structures in crystals are an origin of symmetry breaking in a wide range of dense-phase crystals. Preparation of such analogous structures in framework-phase crystals is of great importance in zeolites but is still a challenge. On the basis of crystal-structure solving and model building, it was found that the two specific intergrowths in MTW zeolite produce this complex fractal and spiral structure. With the structurally determined parameters (spiral pitch h, screw angle θ, and spatial angle ψ) of Burgers circuit, the screw dislocation structure can be constructed by two different dimensional intergrowth sections. Thus the reported complexity of various dimensions in diverse crystals can be unified. Hunting hidden dimensions: It is revealed that the experimentally observed screw dislocation structure in MTW zeolite is constructed by two specific rational intergrowth processes along different dimensions.
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Two-Dimensional Seeded Self-Assembly of a Complex Hierarchical Perylene-Based Heterostructure ()
A complex two-dimensional (2D) hierarchical heterostructure was fabricated by a sequential two-dimensional seeded self-assembly, which consisted of laterally grown nanotubes from one perylene monomer and terminally elongated nanocoils from a similar perylene monomer on microribbon seeds from a third perylene. Because the nanotube and nanocoil monomers can form kinetically trapped off-pathway aggregates to prevent self-nucleation and have similar molecular organizations to different facets of the seeds, the nanotube and nanocoil monomers preferentially nucleate and grow on the seed sides and terminal ends, respectively, to form a complex 2D hierarchical heterostructure. The strategy used in this work can be extended to fabricate other complex nanoarchitectures from small molecules. Location, location: A complex 2D hierarchical heterostructure was fabricated by a sequential seeded self-assembly. This consisted of laterally grown nanotubes from a perylene derivative (blue) and terminally elongated nanocoils from a similar perylene (yellow) on a microribbon seed from a third perylene (red).
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Decacene: On-Surface Generation ()
Acenes are intriguing molecules with unique electronic properties. The difficulties in their preparation owing to low stability under ambient conditions are apparent because successful syntheses of long unsubstituted acenes are still scarce, in spite of the great attention they have attracted. Only unsubstituted acenes up to heptacene have been isolated in bulk, with nonacene being the largest acene detected to date. Herein we use on-surface assisted reduction of tetraepoxy decacene precursors on Au(111) as the key step to generate unprecedented decacene which is visualized and its electronic resonances studied by scanning tunneling microscopy (STM) and spectroscopy (STS). Decathletes: Combined efforts of organic synthesis and on-surface chemistry have led to the preparation of decacene for the first time. An iterative sequence of aryne cycloadditions was used to synthesize stable tetraepoxy precursors which were reduced on Au(111) to obtain unprecedented decacene as visualized by scanning tunneling microscopy (STM).
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Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide Composite ()
A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution. Come full circle: A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution.
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Switchable Stereoselectivity in Bromoaminocyclization of Olefins: Using Brønsted Acids of Anionic Chiral Cobalt(III) Complexes ()
Brønsted acids of anionic chiral CoIII complexes act as bifunctional phase-transfer catalysts to shuttle the substrates across the solvent interface and control stereoselectivity. The diastereomeric chiral CoIII-templated Brønsted acids, with the same chiral ligands, enabled a switch in the enantioselective bromoaminocyclization of olefins to afford the two enantiomers of 2-substituted pyrrolidines with high enantioselectivities (up to 99:1 e.r.). Flip of the switch: Brønsted acids of anionic chiral CoIII complexes act as bifunctional phase-transfer catalysts to shuttle the substrates across the solvent interface and control stereoselectivity. The diastereomeric chiral CoIII-templated Brønsted acids, with the same chiral ligands, enabled a switch in the enantioselective bromoaminocyclization of olefins to afford the two enantiomers of the 2-substituted pyrrolidines with high stereoselectivities.
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Control of Redox Events by Dye Encapsulation Applied to Light-Driven Splitting of Hydrogen Sulfide ()
Solar production of hydrogen by consuming low-value waste products is an attractive pathway that has both economic and environmental benefits. Inspired by the reactive pocket of enzymes, a synthetic platform to combine photocatalytic hydrogen evolution with sulfide oxidation in a one-pot process via control over the location of the electron-transfer steps is developed. The redox-active coordination vessel Ni-TFT, which has an octahedral pocket, encapsulates an organic dye to pre-organize for photocatalytic proton reduction via an oxidative quenching pathway using the nickel corners as catalysts, generating molecular hydrogen and the oxidized dye. The oxidized dye is displaced by a neutral dye and oxidizes sulfide once outside the pocket to give element sulfur. The overall reaction constitutes hydrogen sulfide splitting, forming molecular hydrogen and elemental sulfur, which is analogous to the water-splitting reaction. Split and run: A supramolecular cage that allows a photocatalytic hydrogen evolution to be combined with sulfide oxidation in a one-pot process was developed, by preorganization of the dye controlling the crucial electron-transfer steps. The overall reaction is hydrogen sulfide splitting forming molecular hydrogen and elemental sulfur, which is analogous to the water-splitting reaction.
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Molecular Knots ()
The first synthetic molecular trefoil knot was prepared in the late 1980s. However, it is only in the last few years that more complex small-molecule knot topologies have been realized through chemical synthesis. The steric restrictions imposed on molecular strands by knotting can impart significant physical and chemical properties, including chirality, strong and selective ion binding, and catalytic activity. As the number and complexity of accessible molecular knot topologies increases, it will become increasingly useful for chemists to adopt the knot terminology employed by other disciplines. Here we give an overview of synthetic strategies towards molecular knots and outline the principles of knot, braid, and tangle theory appropriate to chemistry and molecular structure. Thou shalt knot … This Review gives an overview of the field of closed-loop molecular entanglements in terms of their synthesis, and outlines the principles of knot, braid, and tangle theory appropriate to chemistry and molecular structure. The steric restrictions imposed on molecular strands by knotting can impart significant physical and chemical properties, including chirality, strong and selective ion binding, and catalytic activity.
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Colossal Stability of Gas-Phase Trianions: Super-Pnictogens ()
Multiply charged negative ions are ubiquitous in nature. They are stable as crystals because of charge compensating cations; while in solutions, solvent molecules protect them. However, they are rarely stable in the gas phase because of strong electrostatic repulsion between the extra electrons. Therefore, understanding their stability without the influence of the environment has been of great interest to scientists for decades. While much of the past work has focused on dianions, work on triply charged negative ions is sparse and the search for the smallest trianion that is stable against spontaneous electron emission or fragmentation continues. Stability of BeB11(X)123− (X=CN, SCN, BO) trianions is demonstrated in the gas phase, with BeB11(CN)123− exhibiting colossal stability against electron emission by 2.65 eV and against its neutral adduct by 15.85 eV. The unusual stability of these trianions opens the door to a new class of super-pnictogens with potential applications in aluminum-ion batteries. Unusually stable trianions BeB11(CN)123−, BeB11(BO)123−, and BeB11(SCN)123−, were synthesized using the octet and Wade–Mingos electron counting rules simultaneously. In the gas phase, the trianions are stable against spontaneous electron emission by 2.65, 1.30, and 0.59 eV, respectively. The chemistry of the stable trianions mimics that of group 15 elements.
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Mechanically Interlocked Molecules (MIMs)—Molecular Shuttles, Switches, and Machines (Nobel Lecture) ()
Chemistry welcomes a new bond: The mechanical bond has endowed molecules with component parts whose movements can be controlled and monitored. In his Nobel Lecture, J. F. Stoddart describes how being able to template the formation of mechanically interlocked molecules has led to the design and synthesis of shuttles, switches, and machines at the nanoscale.
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An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species ()
A strategy to deliver a well-defined persulfide species in a biological medium is described. Under near physiological conditions, the persulfide prodrug can be activated by an esterase to generate a “hydroxymethyl persulfide” intermediate, which rapidly collapses to form a defined persulfide. Such persulfide prodrugs can be used either as chemical tools to study persulfide chemistry and biology or for future development as H2S-based therapeutic reagents. Using the persulfide prodrugs developed in this study, the reactivity between S-methyl methanethiosulfonate (MMTS) with persulfide was unambiguously demonstrated. Furthermore, a representative prodrug exhibited potent cardioprotective effects in a murine model of myocardial ischemia-reperfusion (MI/R) injury with a bell shape therapeutic profile. A strategy to deliver a well-defined persulfide species in a biological medium is described. Under near physiological conditions, a persulfide prodrug is activated by an esterase to generate a hydroxymethyl persulfide intermediate, which rapidly collapses to form a persulfide. Such prodrugs can be used to study persulfide chemistry and biology or for development as H2S-based therapeutic reagents.
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Processable and Moldable Sodium-Metal Anodes ()
Sodium-ion batteries are similar in concept and function to lithium-ion batteries, but their development and commercialization lag far behind. One obstacle is the lack of a standard reference electrode. Unlike Li foil reference electrodes, sodium is not easily processable or moldable and it deforms easily. Herein we fabricate a processable and moldable composite Na metal anode made from Na and reduced graphene oxide (r-GO). With only 4.5 % percent r-GO, the composite anodes had improved hardness, strength, and stability to corrosion compared to Na metal, and can be engineered to various shapes and sizes. The plating/stripping cycling of the composite anode was significantly extended in both ether and carbonate electrolytes giving less dendrite formation. We used the composite anode in both Na-O2 and Na-Na3V2(PO4)3 full cells. Sodium to GO: An obstacle to the development of sodium-based energy systems is the lack of a standard reference electrode. Sodium deforms easily and if rolled into a film to be used as the reference electrode it is difficult to control its shape and thickness. But sodium with 4.5 % reduced graphene oxide (r-GO), then Na@r-GO composite anodes can be processed and molded and have improved electrochemical properties.
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Fluorous Phase-Directed Peptide Assembly Affords Nano-Peptisomes Capable of Ultrasound-Triggered Cellular Delivery ()
Here, we report the design, synthesis and efficacy of a new class of ultrasound (US)-sensitive self-assembled peptide-based nanoparticle. Peptisomes are prepared via templated assembly of a de novo designed peptide at the interface of fluorinated nanodroplets. Utilizing peptide assembly allows for facile particle synthesis, direct incorporation of bioactive sequences displayed from the particle corona, and the ability to easily encapsulate biologics during particle preparation using a mild solvent exchange procedure. Further, nano-peptisome size can be precisely controlled by simply modulating the starting peptide and fluorinated solvent concentrations during synthesis. Biomolecular cargo encapsulated within the particle core can be directly delivered to the cytoplasm of cells upon US-mediated rupture of the carrier. Thus, nano-peptisomes represent a novel class of US-activated carriers that can shuttle cell-impermeable biomacromolecules into cells with spatial and temporal precision. Burst your bubble: The templated assembly of a de novo designed peptide at the interface of fluorous nanodroplets affords ultrasound-sensitive nano-peptisomes. Acoustic rupture of the carrier at the surface of cells leads to direct intracellular delivery of encapsulated membrane-impermeable biomolecular cargo with spatial and temporal precision.
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Macroscopic Polarization Enhancement Promoting Photo- and Piezoelectric-Induced Charge Separation and Molecular Oxygen Activation ()
Efficient photo- and piezoelectric-induced molecular oxygen activation are both achieved by macroscopic polarization enhancement on a noncentrosymmetric piezoelectric semiconductor BiOIO3. The replacement of V5+ ions for I5+ in IO3 polyhedra gives rise to strengthened macroscopic polarization of BiOIO3, which facilitates the charge separation in the photocatalytic and piezoelectric catalytic process, and renders largely promoted photo- and piezoelectric induced reactive oxygen species (ROS) evolution, such as superoxide radicals (.O2−) and hydroxyl radicals (.OH). This work advances piezoelectricity as a new route to efficient ROS generation, and also discloses macroscopic polarization engineering on improvement of multi-responsive catalysis. Macroscopic polarization enhancement by V5+ replacement in the piezoelectric semiconductor BiOIO3 can greatly facilitate charge separation and provide efficient photo- and piezoelectric-induced molecular oxygen activation. Powerful superoxide and hydroxyl radicals can be thereby produced in abundance.
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An Ionophore-Based Anion-Selective Optode Printed on Cellulose Paper ()
A general anion-sensing platform is reported based on a portable and cost-effective ion-selective optode and a smartphone detector equipped with a color analysis app. In contrast to traditional anion-selective optodes using a hydrophobic polymer and/or plasticizer to dissolve hydrophobic sensing elements, the new optode relies on hydrophilic cellulose paper. The anion ionophore and a lipophilic pH indicator are inkjet-printed and adsorbed on paper and form a “dry” hydrophobic sensing layer. Porous cellulose sheets also allow the sensing site to be modified with dried buffer that prevents any sample pH dependence of the observed color change. A highly selective fluoride optode using an AlIII-porphyrin ionophore is examined as an initial example of this new anion sensing platform for measurements of fluoride levels in drinking water samples. Apart from Lewis acid–base recognition, hydrogen bonding recognition is also compatible with this sensing platform. Cellulose paper as a sole substrate allows adsorption of a lipophilic anion ionophore and pH-sensitive indicator dye to enable heterogeneous anion sensing via an anion-proton co-extraction mechanism. This platform also enables adsorption of a buffer salt as the sample pH adjuster to prevent pH dependence of the optical anion response.
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Shaping Antiaromatic π-Systems by Metalation: Synthesis of a Bowl-Shaped Antiaromatic Palladium Norcorrole ()
The synthesis of a bowl-shaped antiaromatic molecule was achieved through the deformation of a planar antiaromatic porphyrinic π-conjugation system by insertion of palladium into the small cavity of a metal-free norcorrole. The bowl-to-bowl inversion dynamics of the antiaromatic Pd-coordinated norcorrole was determined by variable-temperature 1H NMR spectroscopy. The metal-free norcorrole was prepared from acid-induced demetalation of a copper norcorrole, which was obtained from the intramolecular coupling of a bis(diiododipyrrin) copper complex with copper thiophenecarboxylate. A bowl-shaped antiaromatic molecule was synthesized by deformation of a planar antiaromatic π-conjugation system upon insertion of palladium into the small cavity of a metal-free norcorrole. The latter was prepared from demetalation of a copper norcorrole obtained from the intramolecular coupling of a bis(diiododipyrrin) copper complex with copper thiophenecarboxylate.
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Highly Efficient Chemiluminescence Probe for the Detection of Singlet Oxygen in Living Cells ()
Singlet oxygen is among the reactive oxygen species (ROS) with the shortest life-times in aqueous media because of its extremely high reactivity. Therefore, designing sensors for detection of 1O2 is perhaps one of the most challenging tasks in the field of molecular probes. Herein, we report a highly selective and sensitive chemiluminescence probe (SOCL-CPP) for the detection of 1O2 in living cells. The probe reacts with 1O2 to form a dioxetane that spontaneously decomposes under physiological conditions through a chemiexcitation pathway to emit green light with extraordinary intensity. SOCL-CPP demonstrated promising ability to detect and image intracellular 1O2 produced by a photosensitizer in HeLa cells during photodynamic therapy (PDT) mode of action. Our findings make SOCL-CPP the most effective known chemiluminescence probe for the detection of 1O2. We anticipate that our chemiluminescence probe for 1O2 imaging would be useful in PDT-related applications and for monitoring 1O2 endogenously generated by cells in response to different stimuli. Illuminating singlet oxygen: A chemiluminescence probe for singlet oxygen based on dioxetane formation is described. The dioxetane decomposes by a highly efficient chemiexcitation process to emit green light. The probe was used to detect and image intracellular 1O2 produced by a photosensitizer in HeLa cells during photodynamic therapy.
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Biomimetic Synthesis of Complex Flavonoids Isolated from Daemonorops “Dragon's Blood” ()
The dragonbloodins are a pair of complex flavonoid trimers that have been isolated from the palm tree Daemonorops draco, one of the sources of the ancient resin known as “dragon's blood”. We present a short synthesis that clarifies their relative configurations and sheds light on their origin in Nature. This synthesis features biomimetic cascade reactions that involve both ionic and radical intermediates. The biogenetic relationships between dracorhodin, the dracoflavans C, and the dragonbloodins A1 and A2 are discussed. Dragonbloodin A1 and A2 are two flavonoid trimers that have been isolated from the palm tree Daemonorops draco, one of the sources of “dragon's blood”. Their relative configurations were clarified through an efficient synthesis, which also suggests that the complex molecules form spontaneously from the red colorants of dragon's blood in air.
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Directing the Activation of Donor–Acceptor Cyclopropanes Towards Stereoselective 1,3-Dipolar Cycloaddition Reactions by Brønsted Base Catalysis ()
The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor-acceptor cyclopropanes is presented. It is demonstrated that by applying an optically active bifunctional Brønsted base catalyst, racemic di-cyano cyclopropylketones can be activated to undergo a stereoselective 1,3-dipolar reaction with mono- and polysubstituted nitroolefins. The reaction affords functionalized cyclopentanes with three consecutive stereocenters in high yield and stereoselectivity. Based on the stereochemical outcome, a mechanism in which the organocatalyst activates both the donor-acceptor cyclopropane and nitroolefin is proposed. Finally, chemoselective transformations of the cycloaddition products are demonstrated. Polar ends: The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor-acceptor cyclopropanes is presented. By using an optically active bifunctional Brønsted base catalyst, racemic di-cyano cyclopropylketones can be activated to undergo a stereoselective 1,3-dipolar reaction with mono- and polysubstituted nitroolefins. The reaction affords functionalized cyclopentanes with three contiguous stereocenters in high yield and stereoselectivity.
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Response to Comment on “A Liposomal System Capable of Generating CO2 Bubbles to Induce Transient Cavitation, Lysosomal Rupturing and Cell Necrosis” ()
Leroux et al. performed a set of experiments reported in our study and claim that they failed to reproduce the thermoresponsive liposomal system containing ammonium bicarbonate (ABC) that could trigger drug release under mild heating. We disagree with their assessments and speculate that the different method used by Leroux et al. to prepare the aqueous ABC is the culprit.
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Intermediate Product Regulation in Tandem Solid Catalysts with Multimodal Porosity for High-Yield Synthetic Fuel Production ()
Tandem catalysis is an attractive strategy to intensify chemical technologies. However, simultaneous control over the individual and concerted catalyst performances poses a challenge. We demonstrate that enhanced pore transport within a Co/Al2O3 Fischer–Tropsch (FT) catalyst with hierarchical porosity enables its tandem integration with a Pt/ZSM-5 zeolitic hydrotreating catalyst in a spatially distant fashion that allows for catalyst-specific temperature adjustment. Nevertheless, this system resembles the case of close active-site proximity by mitigating secondary reactions of primary FT α-olefin products. This approach enables the combination of in situ dewaxing with a minimum production of gaseous hydrocarbons (18 wt %) and an up to twofold higher (50 wt %) selectivity to middle distillates compared to tandem pairs based on benchmark mesoporous FT catalysts. An overall 80 % selectivity to liquid hydrocarbons from syngas is attained in one step, attesting to the potential of this strategy for increasing the carbon efficiency in intensified gas-to-liquid technologies. Closely apart: Enhanced molecular transport within a soft-templated catalyst with a meso/macro/macroporous architecture is exploited to channel primary reaction products between two solid catalysts, enabling them to operate in a spatially distant fashion and at different temperatures, while resembling a nanoscale active site proximity. This approach reconciles wax depletion with minimum tail-gas and maximum middle-distillates selectivities in the single-step production of liquid hydrocarbons from syngas.
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Solid-State Transformation of Amorphous Calcium Carbonate to Aragonite Captured by CryoTEM ()
Early-stage reaction mechanisms for aragonite-promoting systems are relatively unknown compared to the more thermodynamically stable calcium carbonate polymorph, calcite. Using cryoTEM and SEM, the early reaction stages taking place during aragonite formation were identified in a highly supersaturated solution using an alcohol–water solvent, and an overall particle attachment growth mechanism was described for the system. In vitro evidence is provided for the solid-state transformation of amorphous calcium carbonate to aragonite, demonstrating the co-existence of both amorphous and crystalline material within the same aragonite needle. This supports non-classical formation of aragonite within both a synthetic and biological context. Solid-state transformation: Observing early stages of aragonite formation using cryoTEM, it is demonstrated that a non-classical mechanism is taking place, including the co-existence of amorphous and crystalline material. This offers key evidence to support nanoparticle assembly mechanisms in both synthetic and biological systems.
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A Challenging Pie to Splice: Drugging the Spliceosome ()
Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical-based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology. Over the last decade, considerable effort has been directed at developing drugs that target the spliceosome. The resulting synthetic and natural product splice modulators have opened new avenues for the interrogation of disease-associated splicing events. In this Minireview, an overview is provided of the recent advances in addressing the chemistry and chemical biology of the spliceosome and modulating its action with small molecules.
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Rational Control of the Selectivity of a Ruthenium Catalyst for Hydrogenation of 4-Nitrostyrene by Strain Regulation ()
Tuning the selectivity of metal catalysts is of paramount importance yet a great challenge. A new strategy to effectively control the selectivity of metal catalysts, by tuning the lattice strain, is reported. A certain amount of Co atoms is introduced into Ru catalysts to compress the Ru lattice, as confirmed by aberration-corrected high-resolution transmission electron microscopy (HRTEM) and X-ray absorption fine structure (XAFS) measurements. We discover that the lattice strain of Ru catalysts can greatly affect their selectivity, and Ru with 3 % lattice compression exhibits extremely high catalytic selectivity for hydrogenation of 4-nitrostyrene to 4-aminostyrene compared to pristine Ru (99 % vs. 66 %). Theoretical studies confirm that the optimized lateral compressive strain facilitates hydrogenation of the nitro group but impedes the hydrogenation of the vinyl group. This study provides a new guideline for designing metal catalysts with high selectivity. Taking the strain: Introducing Co atoms into a Ru catalyst compressed the Ru lattice strain, thus further affecting catalytic selectivity for hydrogenation of 4-nitrostyrene to 4-aminostyrene. Theoretical studies reveal that the optimized lateral compressive strain facilitates hydrogenation of the nitro group but impedes the hydrogenation of the vinyl group.
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In Situ Localization of Enzyme Activity in Live Cells by a Molecular Probe Releasing a Precipitating Fluorochrome ()
Current enzyme-responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited-state intramolecular proton transfer (ESIPT)-based solid-state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme-responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer. A solid-state fluorophore HTPQ that is well-suited to confocal microscopy was developed. HTPQ was used to design an enzyme-responsive, fluorogenic probe (HTPQA) targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion-resistant detection of endogenous ALP in live cells and visualization of ALP levels in Saos-2 and U-2OS osteosarcoma cells and tissue.
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Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Secondary α-(Trifluoromethyl)benzyl Tosylates ()
A palladium-catalyzed C(sp3)−C(sp2) Suzuki–Miyaura cross-coupling of aryl boronic acids and α-(trifluoromethyl)benzyl tosylates is reported. A readily available, air-stable palladium catalyst was employed to access a wide range of functionalized 1,1-diaryl-2,2,2-trifluoroethanes. Enantioenriched α-(trifluoromethyl)benzyl tosylates were found to undergo cross-coupling to give the corresponding enantioenriched cross-coupled products with an overall inversion in configuration. The crucial role of the CF3 group in promoting this transformation is demonstrated by comparison with non-fluorinated derivatives. Only with fluorine: A palladium-catalyzed cross-coupling of secondary α-(trifluoromethyl)benzyl tosylates with (hetero)aryl boronic acids enables the stereoselective synthesis of more than twenty 1,1-diaryl-2,2,2-trifluoroethanes. The cross-coupling was shown to occur with predominant inversion of configuration.
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Copper-Catalyzed Amination of Congested and Functionalized α-Bromocarboxamides with either Amines or Ammonia at Room Temperature ()
There are several reports on the synthesis of alkylamines, but most of the reported methods are not suitable for the synthesis of hindered amines. In this research, we found that a copper catalyst is effective for the formation of congested C−N bonds at room temperature. Control experiments revealed that a copper amide is a key intermediate. Moreover, when a chiral amine was used, a quaternary carbon stereogenic center was created with good selectivity. Bulk up: A copper catalyst system enables the reaction of bulky and functionalized alkyl groups with amines, including ammonia, at room temperature. The key intermediate in this amination reaction is a copper amide.
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Rhodium-Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3-Disubstituted Oxindoles ()
A rhodium-Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation reaction is described. The reductive cyclization of o-bromoaniline-derived acrylamides provides convenient access to 3,3-disubstituted oxindoles in good yields and with excellent enantioselectivity across a range of substrates. We propose that the key cyclization proceeds via a rhodium(III) intermediate. Overall, this method represents an unusual mode of reactivity for rhodium catalysis and is complementary to palladium(0)-catalyzed α-arylation methods. All systems Ar go: A novel approach for the synthesis of 3,3-disubstituted oxindoles was developed using a rhodium-Josiphos chiral catalyst system. This unusual enantioselective rhodium-catalyzed reductive arylation, which functions across a range of substrates, serves as an alternative to palladium(0)-catalyzed α-arylation and does not require the use of a strong base for enolate formation.
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Asymmetric Synthesis of Chiral Cyclopentanes Bearing an All-Carbon Quaternary Stereocenter by Zirconium-Catalyzed Double Carboalumination ()
Herein, we report a zirconium-catalyzed enantio- and diastereoselective inter/intramolecular double carboalumination of unactivated 2-substituted 1,5-dienes, which provides efficient and direct access to chiral cyclopentanes through the generation of two stereocenters, including one all-carbon quaternary stereocenter, generally with excellent diastereo- and high enantioselectivity. This tandem carboalumination process creates two new C−C bonds as well as one C−Al bond, which can be oxidized in situ with O2 or hydrolyzed. Furthermore, the obtained chiral cyclopentanes can be readily functionalized to provide various chiral compounds. All-carbon quaternary stereocenters: A zirconium-catalyzed double carboalumination of various unactivated 1,5-dienes provides efficient access to chiral cyclopentanes with two stereocenters, including one all-carbon quaternary stereocenter, through the formation of two new C−C bonds as well as one C−Al bond with high diastereo- and enantioselectivity.
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A Quadruple-Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS Mutated Cancer Cell Lines ()
We developed a novel PtIV prodrug that simultaneously releases four different bioactive moieties inside the cancer cell. Its cytotoxicity against monolayer cultures (2D) and spheroid (3D) cancer cells is significantly better than cisplatin. It is 200–450-fold more potent than cisplatin against KRAS mutated pancreatic and colon cancers and is 40-fold more selective towards KRAS mutated cells compared to non-cancerous. This is important since RAS proteins play a role in regulating cell differentiation, proliferation, and survival and KRAS is mutated in 90 % of pancreatic adenocarcinomas, 45 % of colorectal cancers, and 35 % of lung adenocarcinomas. The selectivity index, determined by dividing the IC50 value in non-cancerous cells by that of a cancerous cell line, is two-fold better than cisplatin, attesting to preferential cytotoxicity towards neoplastic cells. Four for one: Upon intracellular activation, a dinuclear PtIV complex releases four bioactive agents that attack different cellular targets. This compound is extremely potent especially against highly aggressive KRAS mutated pancreatic and colon cancer cells being 200–450-fold more potent than cisplatin.
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Powder Catalyst Fixation for Post-Electrolysis Structural Characterization of NiFe Layered Double Hydroxide Based Oxygen Evolution Reaction Electrocatalysts ()
Highly active electrocatalysts for the oxygen evolution (OER) reaction are in most cases powder nanomaterials, which undergo substantial changes upon applying the high potentials required for high-current-density oxygen evolution. Owing to the vigorous gas evolution, the durability under OER conditions is disappointingly low for most powder electrocatalysts as there are no strategies to securely fix powder catalysts onto electrode surfaces. Thus reliable studies of catalysts during or after the OER are often impaired. Herein, we propose the use of composites made from precursors of polybenzoxazines and organophilically modified NiFe layered double hydroxides (LDHs) to form a stable and highly conducting catalyst layer, which allows the study of the catalyst before and after electrocatalysis. Characterization of the material by XRD, SEM, and TEM before and after 100 h electrolysis in 5 m KOH at 60 °C and a current density of 200 mA cm−2 revealed previously not observed structural changes. An active and stable OER catalyst was directly fixated on an electrode starting from a NiFe layered double hydroxide (LDH)/polybenzoxazine composite. Owing to its stable immobilization on the electrode, the catalyst can be characterized before and after electrolysis. After electrolysis at 200 mA cm−2 in 5 m KOH for 100 h, previously not reported structural changes were observed for the NiFe LDH.
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High-Level Spectroscopy, Quantum Chemistry, and Catalysis: Not just a Passing Fad ()
Quantum chemistry can be used as a powerful link between theory and experiment for studying reactions in all areas of catalysis. The key feature of this approach is the combination of quantum chemistry with a range of high-level spectroscopic methods. This allows for conclusions to be reached that neither theory nor experiment would have been able to obtain in isolation. A combined approach: This Essay illustrates how quantum chemistry can be used as a powerful link between theory and experiment for studying catalytic reactions. The key feature of the approach is the combination of quantum chemistry with a range of high-level spectroscopic methods. This allows for conclusions to be reached that neither theory nor experiment alone would have been able to obtain.
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Direct Monofluoromethylthiolation with S-(Fluoromethyl) Benzenesulfonothioate ()
An electrophilic shelf-stable monofluoromethylthiolating reagent S-(fluoromethyl) benezenesulfonothioate (1) was developed. In the presence of a copper catalyst, reagent 1 coupled with a variety of aryl boronic acids to give the corresponding monofluoromethylthiolated arenes in high yields. In addition, addition of reagent 1 to alkyl alkenes in the presence of a silver catalyst gave alkyl monofluoromethylthioethers in high yields. An electrophilic shelf-stable monofluoromethylthiolating reagent, S-(fluoromethyl) benzenesulfonothioate (1), was developed. Reagent 1 couples with a variety of aryl boronic acids or unactivated alkenes to give the corresponding monofluoromethylthiolated arenes and alkanes in high yields.
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Copper-Catalyzed Decarboxylative Radical Silylation of Redox-Active Aliphatic Carboxylic Acid Derivatives ()
A decarboxylative silylation of aliphatic N-hydroxyphthalimide (NHPI) esters using Si−B reagents as silicon pronucleophiles is reported. This C(sp3)−Si cross-coupling is catalyzed by copper(I) and follows a radical mechanism, even with exclusion of light. Both primary and secondary alkyl groups couple effectively, whereas tertiary alkyl groups are probably too sterically hindered. The functional-group tolerance is generally excellent, and α-heteroatom-substituted substrates also participate well. This enables, for example, the synthesis of α-silylated amines starting from NHPI esters derived from α-amino acids. The new method extends the still limited number of C(sp3)−Si cross-couplings of unactivated alkyl electrophiles. CO2 neutral: Although seemingly trivial, C(sp3)−Si cross-coupling between unactivated alkyl electrophiles and silicon (pro)nucleophiles had been elusive until recently. The present decarboxylative silylation of N-hydroxyphthalimide (NHPI) esters makes use of Si−B reagents as the source of silicon and is catalyzed by copper(I). This broadly applicable reaction is shown to follow a radical mechanism and also proceeds in the dark.
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Unconventional Route to Uniform Hollow Semiconducting Nanoparticles with Tailorable Dimensions, Compositions, Surface Chemistry, and Near-Infrared Absorption ()
Despite impressive recent advances in the synthesis of lead chalcogenide solid nanoparticles, there are no examples of lead chalcogenide hollow nanoparticles (HNPs) with controlled diameter and shell thickness as current synthetic approaches for HNPs have inherent limitations associated with their complexity, inability to precisely control the dimensions, and limited possibilities with regard to applicable materials. Herein, we report on an unconventional strategy for crafting uniform lead chalcogenide (PbS and PbTe) HNPs with tailorable size, surface chemistry, and near-IR absorption. Amphiphilic star-like triblock copolymers [polystyrene-block-poly(acrylic acid)-block-polystyrene and polystyrene-block-poly(acrylic acid)-block-poly(3,4-ethylenedioxythiophene)] were rationally synthesized and exploited as nanoreactors for the formation of uniform PbS and PbTe HNPs. Compared to their solid counterparts, the near-IR absorption of the HNPs is blue-shifted owing to the hollow interior. This strategy can be readily extended to other types of intriguing low-band-gap HNPs for diverse applications. An unconventional strategy for the synthesis of uniform PbS and PbTe hollow nanoparticles with tailorable sizes, surface chemistry, and near-IR absorption is based on the use of the amphiphilic star-like triblock copolymers polystyrene-block-poly(acrylic acid)-block-polystyrene (PS-b-PAA-b-PS) and polystyrene-block-poly(acrylic acid)-block-poly(3,4-ethylenedioxythiophene) (PS-b-PAA-b-PEDOT) as nanoreactors.
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Stereospecific Decarboxylative Nazarov Cyclization Mediated by Carbon Dioxide for the Preparation of Highly Substituted 2-Cyclopentenones ()
Highly substituted 2-cyclopentenones were stereospecifically and regioselectively constructed with high catalytic efficiency through Lewis-acid catalyzed decarboxylative Nazarov cyclization of the cyclic carbonate derivative, which is prepared by reacting the propargyl alcohol with carbon dioxide in the presence of a silver catalyst. The stereochemistry of the 2-cyclopentenone is strictly controlled by the geometry of the alkene in the starting material. This method is applicable for various substrates. Complete control: Highly substituted 2-cyclopentenones were stereospecifically and regioselectively constructed with high catalytic efficiency through Lewis acid catalyzed decarboxylative Nazarov cyclization of the cyclic carbonate derivative, which was prepared by reacting the propargyl alcohol with carbon dioxide in the presence of a silver catalyst. The stereochemistry of the 2-cyclopentenone is strictly controlled by the geometry of the alkene in the starting material.
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Copper-Induced Topology Switching and Thrombin Inhibition with Telomeric DNA G-Quadruplexes ()
The topological diversity of DNA G-quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol-based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid-phase synthesis. Square-planar coordination to a CuII ion led to the formation of a highly stabilizing intramolecular metal–base tetrad, substituting one G-tetrad in the parent unimolecular G-quadruplex. For the Tetrahymena telomeric repeat, CuII-triggered switching from a hybrid-dominated conformer mixture to an antiparallel topology was observed. CuII-dependent control over a protein–G-quadruplex interaction was shown for the thrombin–tba pair (tba=thrombin-binding aptamer). Copper is all it needs: A glycol-based pyridine ligand has been incorporated four times into human and Tetrahymena telomeric repeat DNA sequences. Copper(II) coordination either stabilizes a unimolecular G-quadruplex or induces a topology change from a conformer mixture to an antiparallel strand orientation as confirmed by thermal denaturation, CD studies, and simulations.
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Enhanced Carbon Dioxide Electroreduction to Carbon Monoxide over Defect-Rich Plasma-Activated Silver Catalysts ()
Efficient, stable catalysts with high selectivity for a single product are essential if electroreduction of CO2 is to become a viable route to the synthesis of industrial feedstocks and fuels. A plasma oxidation pre-treatment of silver foil enhances the number of low-coordinated catalytically active sites, which dramatically lowers the overpotential and increases the activity of CO2 electroreduction to CO. At −0.6 V versus RHE more than 90 % Faradaic efficiency towards CO was achieved on a pre-oxidized silver foil. While transmission electron microscopy (TEM) and operando X-ray absorption spectroscopy showed that oxygen species can survive in the bulk of the catalyst during the reaction, quasi in situ X-ray photoelectron spectroscopy showed that the surface is metallic under reaction conditions. DFT calculations reveal that the defect-rich surface of the plasma-oxidized silver foils in the presence of local electric fields drastically decrease the overpotential of CO2 electroreduction. Plasma-activation: Silver catalysts activated with an oxygen plasma treatment show extraordinary improvement for CO2 electroreduction compared to flat silver surfaces. Electric field effects on the defect-rich plasma-treated surface promote reduction of CO2 to CO at low overpotentials.
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Annulative π-Extension (APEX): Rapid Access to Fused Arenes, Heteroarenes, and Nanographenes ()
The annulative π-extension (APEX) reaction has the potential to have a tremendous impact on the fields of materials science and bioimaging, as well as on the pharmaceutical/agrochemical industries, since it allows access to fused aromatic systems from relatively simple aromatic compounds in a single step. Typically, an APEX reaction facilitates a one-pot π-extension without the need to prefunctionalize the aromatic compounds. This advantageous feature is extremely useful for tuning and modifying molecular properties in the last step of a synthesis. In this Review, the progress and applications of APEX reactions of unfunctionalized arenes and heteroarenes are described. Tip top: The annulative π-extension (APEX) reaction has the potential to have a tremendous impact on the fields of materials science and pharmaceutical/agrochemical industries, since it can access fused aromatic systems from relatively simple aromatic compounds in a single step. In this Review, the progress and applications of APEX reactions to form unfunctionalized arenes, heteroarenes, and nanographenes are described.
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Chemistry Has a Commitment to Life ()
“… Science that only serves its own interests, that looks away when things get uncomfortable, or that surveys favored territories rather than boldly and curiously breaking new ground will endanger society's trust in the scientific search for truth. This is not a good perspective for a learned society. As a community with responsibilities and values, the GDCh must cultivate a culture that has the well-being of the entire population and the planet in mind …” Read more in the Editorial by Thisbe K. Lindhorst.
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Total Syntheses of the Reported Structures of Curcusones I and J through Tandem Gold Catalysis ()
Total syntheses of the reported structures of the rhamnofolane diterpene natural products curcusones I and J in racemic form were achieved. The synthetic strategy features a novel tandem gold-catalyzed furan formation and furan–allene [4+3] cycloaddition to build the 5,7-fused ring system with an oxa-bridge in one step, and a stereoselective exo-Diels–Alder reaction to form the 6-membered ring. The newly developed tandem gold catalysis is quite general and can be scaled up. Our syntheses suggest that structural revisions of curcusones I and J are needed. A change is gonna come: Total syntheses of the reported structures of the diterpene natural products curcusones I and J through a novel tandem gold-catalyzed furan formation and furan–allene [4+3] cycloaddition to build the 5,7-fused ring system, and an exo-Diels–Alder reaction to form the 6-membered ring, is described. These syntheses revealed that the structural assignment of curcusones I and J needs revision.
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Fervent Hype behind Magnesium Batteries: An Open Call to Synthetic Chemists—Electrolytes and Cathodes Needed ()
Magnesium metal is a superior anode which has double the volumetric capacity of lithium metal and has a negative reduction potential of −2.37 V vs. the standard hydrogen electrode. A major benefit of magnesium is the apparent lack of dendrite formation during charging which is one of the crucial concerns of using a lithium metal anode. In this Review, we highlight the foremost research in the development of electrolytes and cathodes and discuss some of the significant challenges which must be overcome in realizing a practical magnesium battery. 100 years after Grignard's Nobel Prize: Magnesium chemistry has been resurrected by the promise of a magnesium battery to rival the lithium battery. This Review is an invitation to synthetic chemists to enter and boost this hot energy storage field to the next level.
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Alkynes as Electrophilic or Nucleophilic Allylmetal Precursors in Transition-Metal Catalysis ()
Diverse late transition metal catalysts convert terminal or internal alkynes into transient allylmetal species that display electrophilic or nucleophilic properties. Whereas classical methods for the generation of allylmetal species often form stoichiometric by-products, the recent use of alkynes as allylmetal precursors enables completely atom-efficient catalytic processes to be carried out, including enantioselective transformations. The best of both worlds: Diverse late transition metal catalysts can convert terminal or internal alkynes into transient allylmetal species that display electrophilic or nucleophilic properties. The use of alkynes as allylmetal precursors enables completely atom-efficient catalytic processes to be carried out, including enantioselective transformations.
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Transforming Olefins into γ,δ-Unsaturated Nitriles through Copper Catalysis ()
We have developed a strategy to transform olefins into homoallylic nitriles through a mechanism that combines copper catalysis with alkyl nitrile radicals. The radicals are easily generated from alkyl nitriles in the presence of the mild oxidant di-tert-butyl peroxide. This cross-dehydrogenative coupling between simple olefins and alkylnitriles bears advantages over the conventional use of halides and toxic cyanide reagents. With this method, we showcase the facile synthesis of a flavoring agent, a natural product, and a polymer precursor from simple olefins. When two become one: A strategy was developed for transforming olefins into homoallylic nitriles through a mechanism that combines copper catalysis with alkyl nitrile radicals. The radicals are easily generated from alkyl nitriles in the presence of the mild oxidant di-tert-butyl peroxide. This cross-dehydrogenative coupling between simple olefins and alkylnitriles bears advantages over the conventional use of halides and toxic cyanide reagents.
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Development of New Supramolecular Lyotropic Liquid Crystals and Their Application as Alignment Media for Organic Compounds ()
Most alignment media for the residual dipolar coupling (RDC) based molecular structure determination of small organic compounds consist of rod-like polymers dissolved in organic solvents or of swollen cross-linked polymer gels. Thus far, the synthesis of polymer-based alignment media has been a challenging process, which is often followed by a time-consuming sample preparation. We herein propose the use of non-polymeric alignment media based on benzenetricarboxamides (BTAs), which self-assemble into rod-like supramolecules. Our newly found supramolecular lyotropic liquid crystals (LLCs) are studied in terms of their LLC properties and their suitability as alignment media in NMR spectroscopy. Scalable enantiodifferentiating properties are introduced through a sergeant-and-soldier principle by blending achiral with chiral substituted BTAs. All lined up: New lyotropic liquid-crystalline phases based on benzenetricarboxamides are used as alignment media for organic solvents. A chiral alignment medium can be obtained by blending a chiral benzenetricarboxamide into an achiral lyotropic liquid crystal at a molar ratio as low as 190:1.
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Bioinspired, Size-Tunable Self-Assembly of Polymer–Lipid Bilayer Nanodiscs ()
Polymer-based nanodiscs are valuable tools in biomedical research that can offer a detergent-free solubilization of membrane proteins maintaining their native lipid environment. Herein, we introduce a novel ca. 1.6 kDa SMA-based polymer with styrene:maleic acid moieties that can form nanodiscs containing a planar lipid bilayer which are useful to reconstitute membrane proteins for structural and functional studies. The physicochemical properties and the mechanism of formation of polymer-based nanodiscs are characterized by light scattering, NMR, FT-IR, and TEM. A remarkable feature is that nanodiscs of different sizes, from nanometer to sub-micrometer diameter, can be produced by varying the lipid-to-polymer ratio. The small-size nanodiscs (up to ca. 30 nm diameter) can be used for solution NMR spectroscopy studies whereas the magnetic-alignment of macro-nanodiscs (diameter of > ca. 40 nm) can be exploited for solid-state NMR studies on membrane proteins. Discrete bilayers: Lipid bilayer nanodiscs of different size are formed by using modified styrene maleic acid co-polymer. The small-size nanodiscs (up to ca. 30 nm diameter) can be used for solution NMR spectroscopy studies whereas the magnetic-alignment of large-size nanodiscs (or macro-nanodiscs with a diameter of >40 nm) can be exploited for solid-state NMR studies on membrane proteins.
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Electrophilic Amination with Nitroarenes ()
An exceptionally general electrophilic amination, which directly transforms commercially available nitroarenes into alkylated aromatic aminoboranes with zinc organyl compounds was developed. The reaction starts with a two-step partial reduction of the nitro group to a nitrenoid, which is used in situ as the electrophilic amination reagent. To facilitate isolation, the resulting air- and moisture-sensitive aminoboranes were reacted with a range of electrophiles. The method not only represents a direct transformation of nitro compounds into electrophilic amination reagents but also provides an elegant alternative to dehydrocoupling methods for the generation of aminoboranes. Nitro-Power! An exceptionally general electrophilic amination of zinc organyl compounds was developed, and yields alkylated aromatic aminoboranes from commercially available nitroarenes. The partially reduced nitro group is directly engaged as an electrophilic nitrogen intermediate. The aminoboranes were reacted with electrophiles, thereby incorporating two different substituents at the N atom of the former nitro group in a one-pot procedure.
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Photon-Induced Near-Field Electron Microscopy of Eukaryotic Cells ()
Photon-induced near-field electron microscopy (PINEM) is a technique to produce and then image evanescent electromagnetic fields on the surfaces of nanostructures. Most previous applications of PINEM have imaged surface plasmon-polariton waves on conducting nanomaterials. Here, the application of PINEM on whole human cancer cells and membrane vesicles isolated from them is reported. We show that photons induce time-, orientation-, and polarization-dependent evanescent fields on the surfaces of A431 cancer cells and isolated membrane vesicles. Furthermore, the addition of a ligand to the major surface receptor on these cells and vesicles (epidermal growth factor receptor, EGFR) reduces the intensity of these fields in both preparations. We propose that in the absence of plasmon waves in biological samples, these evanescent fields reflect the changes in EGFR kinase domain polarization upon ligand binding. Caught in the act: Accurate synchronization of femtosecond laser and electron pulses in an electron microscope enables the formation and visualization of electromagnetic fields on the surface of eukaryotic cells. These fields decay on the femtosecond timescale and are sensitive to conformational changes in the membrane proteins on the cell surface.
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Asymmetric Synthesis of Secondary and Tertiary Boronic Esters ()
Non-racemic chiral boronic esters are recognised as immensely valuable building blocks in modern organic synthesis. Their stereospecific transformation into a variety of functional groups—from amines and halides to arenes and alkynes—along with their air and moisture stability, has established them as an important target for asymmetric synthesis. Efforts towards the stereoselective synthesis of secondary and tertiary alkyl boronic esters have spanned over five decades and are underpinned by a wealth of reactivity platforms, drawing on the unique and varied reactivity of boron. This Review summarizes strategies for the asymmetric synthesis of alkyl boronic esters, from the seminal hydroboration methods of H. C. Brown to the current state of the art. Non-racemic chiral boronic esters are immensely valuable building blocks in modern organic synthesis. Their stereospecific transformation into a variety of functional groups, along with their air and moisture stability, has established them as an important target for asymmetric synthesis. Methods for their asymmetric synthesis now span a wealth of reactivity platforms.
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Cover Picture: Competition between Arene–Perfluoroarene and Charge-Transfer Interactions in Organic Light-Harvesting Systems (Angew. Chem. Int. Ed. 35/2017) ()
Pass with flying colors Efficient energy transfer from a charge-transfer host to an arene–perfluoroarene dopant generates stable white-light-emitting crystals. In their Communication on page 10352 ff., W. P. Hu et al. describe competing intermolecular charge-transfer and arene–perfluoroarene interactions in blue-light-emitting pyrene–octafluoronaphthalene cocrystals doped with an orange-light-emitting pyrene–1,2,4,5-tetracyanobenzene complex.
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Inside Cover: Crystalline Hollow Microrods for Site-Selective Enhancement of Nonlinear Photoluminescence (Angew. Chem. Int. Ed. 35/2017) ()
In the hands of the monkey god Sun Wukong hollow-structured microcrystals produce spatially resolved optical codes upon illumination with near-infrared light. In their Communication on page 10383 ff., F. Wang et al. reveal that light scattering and reflection by the inner walls of the microrods modulate light intensity across the structure. As a result, the electric field proximal to the inner walls is enhanced, and bright optical emissions are observed around the holes.
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Inside Back Cover: A Molecular Boroauride: A Donor–Acceptor Complex of Anionic Gold (Angew. Chem. Int. Ed. 35/2017) ()
Gold is unusual among the transition metals in that it is stable as an anion (auride). Using a diphosphine ligand derived from diboraanthracene, a donor–acceptor complex of anionic gold has been isolated. In their Communication on page 10413 ff., W. H. Harman et al. show that the auride complex can be reversibly oxidized by two electrons to a cationic gold complex in which the diboraanthracene dissociates, enabling a formal Au(I/−I) redox process.
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Back Cover: Living and Conducting: Coating Individual Bacterial Cells with In Situ Formed Polypyrrole (Angew. Chem. Int. Ed. 35/2017) ()
Coating individual bacterial cells with in situ formed polypyrrole is described by J. S. C. Loo, B. Cao, J. R. Zhang, J.-J. Zhu et al. in their Communication on page 10516 ff. The coated polypyrrole can serve as a conductive medium as well as a protecting layer. Enhanced direct contact-based extracellular electron transfer and improved viability of bacterial cells are observed when polypyrrole-coated exoelectrogenic bacteria are employed as an anode in microbial fuel cells.
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Frontispiece: Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives ()
Hydroxylation In their Communication on page 10324 ff., O. Shoji, Y. Watanabe et al. show that certain amino acid derivatives efficiently activate cytochrome P450BM3 for the direct hydroxylation of benzene to phenol.
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Editorial: New 1.2 GHz NMR Spectrometers— New Horizons? ()
The latest ultrahigh-field NMR spectrometers are a huge technological challenge that require large financial investments. In his Guest Editorial, Harald Schwalbe justifies the need for spectrometers with higher magnetic field strengths. The important results from previous generations of high-field NMR spectrometers are discussed, and research areas are identified that will benefit from the latest spectrometers.
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Graphical Abstract: Angew. Chem. Int. Ed. 35/2017 ()

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Spotlights on our sister journals: Angew. Chem. Int. Ed. 35/2017 ()

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H. Tom Soh ()
“My favorite food is Korean BBQ. When I'm frustrated, I do yoga. ...” This and more about H. Tom Soh can be found on page 10278.
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Wissenschaftspreis 2017: T. Beck / Elected to the Heidelberg Academy of Sciences and František Šorm Memorial Medal: A. Marx / Ruhrpreis für Kunst und Wissenschaft: R. Schlögl / Karl Ziegler Guest Professorship: A. H. Hoveyda ()

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“Super-Reducing” Photocatalysis: Consecutive Energy and Electron Transfers with Polycyclic Aromatic Hydrocarbons ()
Donation welcome: Recent developments in visible-light photocatalysis allow the utilization of increasingly negative reduction potentials. Successive energy and electron transfer with polycyclic aromatic hydrocarbons enables the catalytic formation of strongly reducing arene radical anions, classical stoichiometric reagents for one-electron reduction in organic synthesis.
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Borylenes: An Emerging Class of Compounds ()
Free borylenes (R–B:) have only been spectroscopically characterized in the gas phase or in matrices at very low temperatures. However, in recent years, a few mono- and bis(Lewis base)-stabilized borylenes have been isolated. In both of these compounds the boron atom is in the formal oxidation state +I which contrasts with classical organoboron derivatives wherein the element is in the +III oxidation state. Mono(Lewis base)-stabilized borylenes are isoelectronic with singlet carbenes, and their reactivity mimics to some extent that of transition metals. They can activate small molecules, such as H2, and coordinate an additional ligand; in other words, they are boron metallomimics. Bis(Lewis base)borylene adducts are isoelectronic with amines and phosphines. In contrast to boranes, which act as electron acceptors and thus Lewis acids, they are electron-rich and act as ligands for transition metals. Organoboron as mimics for carbenes and amines: In contrast to classical organoboron derivatives that act as Lewis acids and in which the boron is in the +III oxidation state, mono- and bis(Lewis base)borylene adducts have nucleophilic character and a boron atom in the +I oxidation state. This is a field in its infancy with a lot that remains to be discovered.
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New Modalities for Challenging Targets in Drug Discovery ()
Our ever-increasing understanding of biological systems is providing a range of exciting novel biological targets, whose modulation may enable novel therapeutic options for many diseases. These targets include protein–protein and protein–nucleic acid interactions, which are, however, often refractory to classical small-molecule approaches. Other types of molecules, or modalities, are therefore required to address these targets, which has led several academic research groups and pharmaceutical companies to increasingly use the concept of so-called “new modalities”. This Review defines for the first time the scope of this term, which includes novel peptidic scaffolds, oligonucleotides, hybrids, molecular conjugates, as well as new uses of classical small molecules. We provide the most representative examples of these modalities to target large binding surface areas such as those found in protein–protein interactions and for biological processes at the center of cell regulation. Out of the box: A new generation of molecules, including novel peptides, oligonucleotides, hybrids, and molecular conjugates, is enabling novel strategies to address challenging targets and biological processes at the center of cell regulation. This Review defines these “new modalities”, and highlights how progress in this area is now leading to a range of novel drug candidates.
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Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives ()
The selective hydroxylation of benzene to phenol, without the formation of side products resulting from overoxidation, is catalyzed by cytochrome P450BM3 with the assistance of amino acid derivatives as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1 when N-heptyl-l-proline modified with l-phenylalanine (C7-l-Pro-l-Phe) was used as the decoy molecule. This work shows that amino acid derivatives with a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild-type P450BM3. This method for non-native substrate hydroxylation by wild-type P450BM3 has the potential to expand the utility of P450BM3 for biotransformations. Amino acid derivatives, with structures that are totally different from those of fatty acids, efficiently activate cytochrome P450BM3 for the direct hydroxylation of benzene to phenol. The catalytic turnover rate and total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1, respectively.
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Catalytic Stereoselective 1,4-Addition Reactions Using CsF on Alumina as a Solid Base: Continuous-Flow Synthesis of Glutamic Acid Derivatives ()
A novel methodology using CsF⋅Al2O3 as a highly efficient, environmentally benign, and reusable solid-base catalyst was developed to synthesize glutamic acid derivatives by stereoselective 1,4-addition of glycine derivatives to α,β-unsaturated esters. CsF⋅Al2O3 showed not only great selectivity toward 1,4-addtion reactions by suppressing the undesired formation of pyrrolidine derivations by [3+2] cycloadditions, but also offered high yields for the 1,4-adduct with excellent anti diastereoselectivities. The catalyst was well characterized by using XRD, 19F MAS-NMR and 19F NMR spectroscopy, FT-IR, CO2-TPD, and XPS. And highly basic F from Cs3AlF6 was identified as the most probable active basic site for the 1,4-addition reactions. Continuous-flow synthesis of 3-methyl glutamic acid derivative was successfully demonstrated by using this solid-base catalysis. A solid base: A method to synthesize glutamic acid derivatives by the highly stereoselective 1,4-addition of glycine derivatives to α,β-unsaturated esters, using CsF⋅Al2O3 as a reusable solid-base catalyst, was developed for both batch and continuous-flow systems. Cs3AlF6 was identified as the active basic site for the addition reaction.
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Size Dependence of Doping by a Vacancy Formation Reaction in Copper Sulfide Nanocrystals ()
Doping of nanocrystals (NCs) is a key, yet underexplored, approach for tuning of the electronic properties of semiconductors. An important route for doping of NCs is by vacancy formation. The size and concentration dependence of doping was studied in copper(I) sulfide (Cu2S) NCs through a redox reaction with iodine molecules (I2), which formed vacancies accompanied by a localized surface plasmon response. X-ray spectroscopy and diffraction reveal transformation from Cu2S to Cu-depleted phases, along with CuI formation. Greater reaction efficiency was observed for larger NCs. This behavior is attributed to interplay of the vacancy formation energy, which decreases for smaller sized NCs, and the growth of CuI on the NC surface, which is favored on well-defined facets of larger NCs. This doping process allows tuning of the plasmonic properties of a semiconductor across a wide range of plasmonic frequencies by varying the size of NCs and the concentration of iodine. Controlled vacancy doping of NCs may be used to tune and tailor semiconductors for use in optoelectronic applications. Vacancy formation and plasmon response were analyzed in Cu2S semiconducting nanocrystals (NCs) treated with iodine (I2). The redox reaction between Cu2S and I2 creates vacancies in the Cu2S phase that increase in number with NC size. The plasmonic response can be tuned either by the size of the NCs or by the doping level of holes, which is governed by the I/Cu ratio.
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A Porphyrin Complex as a Self-Conditioned Electrode Material for High-Performance Energy Storage ()
The novel functionalized porphyrin [5,15-bis(ethynyl)-10,20-diphenylporphinato]copper(II) (CuDEPP) was used as electrodes for rechargeable energy-storage systems with an extraordinary combination of storage capacity, rate capability, and cycling stability. The ability of CuDEPP to serve as an electron donor or acceptor supports various energy-storage applications. Combined with a lithium negative electrode, the CuDEPP electrode exhibited a long cycle life of several thousand cycles and fast charge–discharge rates up to 53 C and a specific energy density of 345 Wh kg−1 at a specific power density of 29 kW kg−1. Coupled with a graphite cathode, the CuDEPP anode delivered a specific power density of 14 kW kg−1. Whereas the capacity is in the range of that of ordinary lithium-ion batteries, the CuDEPP electrode has a power density in the range of that of supercapacitors, thus opening a pathway toward new organic electrodes with excellent rate capability and cyclic stability. Give and take: Electrodes based on a copper porphyrin showed excellent capacity retention over several thousand cycles and very fast charge–discharge rates, thus opening a pathway to organic electrode materials with the capacity of a lithium-ion battery and the rate capability of a good supercapacitor. The ability of the porphyrin complex to serve as an electron donor or acceptor is advantageous for various energy-storage applications (see picture).
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Gold(Core)–Lead(Shell) Nanoparticle-Loaded Titanium(IV) Oxide Prepared by Underpotential Photodeposition: Plasmonic Water Oxidation ()
Underpotential photodeposition of Pb yields an ultrathin shell layer on the Au(111) surface of Au nanoparticle(NP)-loaded TiO2 (Au/TiO2) with heteroepitaxial nanojunctions. The localized surface plasmon resonance of Au/TiO2 undergoes no damping with the Pb-shell formation, and the Pb shell offers resistance to aerobic oxidation. Mesoporous films comprising the Au(core)–Pb(shell) NP-loaded TiO2 and unmodified Au/TiO2 were formed on fluorine-doped tin oxide (FTO) electrode. Using them as the photoanode, photoelectrochemical cells were fabricated, and the photocurrent was measured under illumination of simulated sunlight. The photocurrent for water splitting is dramatically enhanced by the Pb-shell formation. The photoelectrochemical measurements of the hot-electron lifetime and density functional theory calculations for model clusters indicate that the Pb-shell effect originates from the charge separation enhancement. Lead on: Underpotential photodeposition of Pb yields an ultrathin shell layer on the Au(111) surface of Au nanoparticle-loaded TiO2 (Au/TiO2). By incorporating this system in a photoanode, the photocurrent for water splitting is dramatically enhanced as a result of the Pb-shell formation.
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Competition between Arene–Perfluoroarene and Charge-Transfer Interactions in Organic Light-Harvesting Systems ()
Two typical types of luminescent organic cocrystals comprising pyrene–octafluoronaphthalene (pyrene–OFN) and pyrene–1,2,4,5-tetracyanobezene (pyrene–TCNB) were developed by a simple supramolecular assembly strategy. The cocrystals exhibit distinct optical properties because of their different intermolecular interaction modes; that is, arene–perfluoroarene (AP) and charge-transfer (CT) interactions. Unexpectedly, a pyrene–TCNB system with strong CT interactions was incorporated into a pyrene–OFN host as a robust guest to generate white-light emission (WLE). In the supramolecular cocrystal system, an efficient energy-transfer process from pyrene–OFN to pyrene–TCNB occurred because of the well-matched spectra of the constituents and a desirable energy donor/acceptor (D/A) distance. The present competitive intermolecular interaction strategy could be applied to the fabrication of more complicated organic light-harvesting systems. Luminescent lightsabers: Stable white-light-emitting crystals containing pyrene–octafluoronaphthalene (pyrene–OFN) cocrystals doped with pyrene–1,2,4,5- tetracyanobenzene (pyrene–TCNB) integrate competitive intermolecular charge-transfer and arene–perfluoroarene interactions. Efficient energy transfer from the charge-transfer host to the arene–perfluoroarene dopant is observed.
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Unique Spectral Overlap and Resonant Energy Transfer between Europium(II) and Ytterbium(III) Cations: No Quantum Cutting ()
Samples of the Ca3Sc2Si3O12 (CSS) host singly doped with Eu2+ or Yb3+, doubly doped with Eu2+ and Yb3+, and triply doped with Ce3+, Eu2+ and Yb3+ were synthesized by a sol–gel combustion process under reducing conditions. Unlike previous reports of Eu2+Yb3+ energy transfer in other systems, the energy transfer is resonant in the CSS host and the transfer efficiency reaches 100 % for lightly doped samples. The transfer mechanism is multipolar rather than electron transfer for the sample compositions employed herein. The emission intensity of Yb3+ is further enhanced by co-doping with Ce3+ in addition to Eu2+. The quantum efficiencies of the doped materials range between 9 % and 93 %. Harvesting solar energy: Eu2+ or Yb3+ singly, Eu2+ and Yb3+ doubly, and Ce3+, Eu2+, and Yb3+ triply doped Ca3Sc2Si3O12 (CSS) host lattices were synthesized by a sol–gel combustion process under reducing conditions. The triply doped system is used for harvesting solar energy and converting it to Yb3+ near-infrared emission (dd=dipole–dipole and dq=dipole–quadrupole interactions, ET=electron transfer).
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Boronic Acid Functionalized Photosensitizers: A Strategy To Target the Surface of Bacteria and Implement Active Agents in Polymer Coatings ()
Advanced methods for preventing and controlling hospital-acquired infections via eradication of free-floating bacteria and bacterial biofilms are of great interest. In this regard, the attractiveness of unconventional treatment modalities such as antimicrobial photodynamic therapy (aPDT) continues to grow. This study investigated a new and innovative strategy for targeting polysaccharides found on the bacterial cell envelope and the biofilm matrix using the boronic acid functionalized and highly effective photosensitizer (PS) silicon(IV) phthalocyanine. This strategy has been found to be successful in treating planktonic cultures and biofilms of Gram-negative E. coli. An additional advantage of boronic acid functionality is a possibility to anchor the tailor made PS to poly(vinyl alcohol) and to fabricate a self-disinfecting coating. Making and breaking barriers: The boronic acid–diol interaction was used to anchor a photosensitizer into the bacterial cell surface and biofilm matrix and break the barrier by photodynamic action. The same functional group enables implementation of the active agent in a poly(vinyl alcohol) coating, providing a photo-bactericidal barrier against microbial adhesion.
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Redox-Driven Migration of Copper Ions in the Cu-CHA Zeolite as Shown by the In Situ PXRD/XANES Technique ()
Using quasi-simultaneous in situ PXRD and XANES, the direct correlation between the oxidation state of Cu ions in the commercially relevant deNOx NH3-SCR zeolite catalyst Cu-CHA and the Cu ion migration in the zeolitic pores was revealed during catalytic activation experiments. A comparison with recent reports further reveals the high sensitivity of the redox-active centers concerning heating rates, temperature, and gas environment during catalytic activation. Previously, Cu+ was confirmed present only in the 6R. Results verify a novel 8R monovalent Cu site, an eventually large Cu+ presence upon heating to high temperatures in oxidative conditions, and demonstrate the unique potential in combining in situ PXRD and XANES techniques, with which both oxidation state and structural location of the redox-active centers in the zeolite framework could be tracked. Quasi-simultaneous in situ PXRD/XANES was used to show the direct correlation between oxidation state and Cu ion migration in the commercially relevant deNOx zeolite catalyst Cu-CHA. Results reveal a surprisingly severe auto-reduction of Cu in oxidative conditions above 400 °C, verify a possible 8R site for Cu+ from heating in inert conditions, and demonstrate the potential of quasi-simultaneous PXRD and XANES techniques.
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Phosphorene Co-catalyst Advancing Highly Efficient Visible-Light Photocatalytic Hydrogen Production ()
Transitional metals are widely used as co-catalysts boosting photocatalytic H2 production. However, metal-based co-catalysts suffer from high cost, limited abundance and detrimental environment impact. To date, metal-free co-catalyst is rarely reported. Here we for the first time utilized density functional calculations to guide the application of phosphorene as a high-efficiency metal-free co-catalyst for CdS, Zn0.8Cd0.2S or ZnS. Particularly, phosphorene modified CdS shows a high apparent quantum yield of 34.7 % at 420 nm. This outstanding activity arises from the strong electronic coupling between phosphorene and CdS, as well as the favorable band structure, high charge mobility and massive active sites of phosphorene, supported by computations and advanced characterizations, for example, synchrotron-based X-ray absorption near edge spectroscopy. This work brings new opportunities to prepare highly-active, cheap and green photocatalysts. Density functional calculations were used to direct the design of phosphorene as a metal-free co-catalyst promoting photocatalytic H2 production in metal sulfide photocatalyst systems. The enhanced photocatalytic performance arises from the pronounced electronic coupling between metal sulfides and phosphorene, together with its advantageous band structure and excellent charge carrier mobility.
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Full Selectivity Control in Cobalt(III)-Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism ()
Selectivity control in hydroarylation-based C−H alkylation has been dominated by steric interactions. A conceptually distinct strategy that exploits the programmed switch in the C−H activation mechanism by means of cobalt catalysis is presented, which sets the stage for convenient C−H alkylations with unactivated alkenes. Detailed mechanistic studies provide compelling evidence for a programmable switch in the C−H activation mechanism from a linear-selective ligand-to-ligand hydrogen transfer to a branched-selective base-assisted internal electrophilic-type substitution. Sterically hindered carboxylate additives promote cobalt-catalyzed C−H alkylation (alkyl=Alk) of unactivated alkenes. Bulky additives switch on a base-assisted internal electrophilic-type substitution (BIES) C−H activation mechanism, thereby favoring congested Markovnikov products. Without additive, a linear-selective ligand-to-ligand hydrogen transfer (LLHT) mechanism occurs.
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Crystalline Hollow Microrods for Site-Selective Enhancement of Nonlinear Photoluminescence ()
A class of one-dimensional hollow microstructure is described, which was formed by a kinetically controlled crystal growth process. A hexagonal-phase NaYbF4 microrod comprising isolated holes along the longitudinal axis was synthesized by a one-pot hydrothermal method with the assistance of citrate ligands. The structural void feature modulates light intensity across the microrods as a result of interference arising from light scattering and reflection by the inner walls. A single crystal comprising a structural void was doped with upconverting lanthanide ions. Upon near-infrared excitation of the doped crystal spatially resolvable optical codes were produced. Hollow-structured microcrystals of hexagonal phase NaYbF4 produce nonlinear photoluminescence upon illumination with near-infrared light. Light scattering and reflection by the inner walls of the microrod modulate light intensity across the structure. Spatially resolved optical codes are attained when the irradiated material is doped with upconverting lanthanide ions.
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Highly Syndiotactic or Isotactic Polyhydroxyalkanoates by Ligand-Controlled Yttrium-Catalyzed Stereoselective Ring-Opening Polymerization of Functional Racemic β-Lactones ()
Reported herein is the first stereoselective controlled ROP of a specific family of racemic functional β-lactones, namely 4-alkoxymethylene-β-propiolactones (BPLORs). This process is catalyzed by an yttrium complex stabilized by a nonchiral tetradentate amino alkoxy bisphenolate ligand {ONOOR′2}2−, which features both a good activity and a high degree of control over the molar masses of the resulting functional poly(3-hydroxyalkanoate)s. A simple modification of the R′ substituents in ortho and para position on the ligand platform allows for a complete reversal from virtually pure syndioselectivity (Ps up to 0.91 with R′=cumyl) to very high isoselectivity (Pi up to 0.93 with R′=Cl), as supported by DFT insights. This is the first example of a highly isoselective ROP of a racemic chiral β-lactone. Make your choice: Highly syndiotactic or isotactic polyhydroxyalkanoates were obtained from racemic mixtures of functional alkoxymethylene-β-lactones in an yttrium-catalyzed ring-opening polymerization. The selectivity can be completely switched by a simple modification of substituents on the catalyst ligand.
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CO2-Sourced α-Alkylidene Cyclic Carbonates: A Step Forward in the Quest for Functional Regioregular Poly(urethane)s and Poly(carbonate)s ()
Described is a robust platform for the synthesis of a large diversity of novel functional CO2-sourced polymers by exploiting the regiocontrolled ring-opening of α-alkylidene carbonates by various nucleophiles. The reactivity of α-alkylidene carbonates is dictated by the exocyclic olefinic group. The polyaddition of CO2-sourced bis(α-alkylidene carbonate)s (bis-αCCs) with primary and secondary diamines provides novel regioregular functional poly(urethane)s. The reactivity of bis-αCCs is also exploited for producing new poly(β-oxo-carbonate)s by organocatalyzed polyaddition with a diol. This synthesis platform provides new functional variants of world-class leading polymer families (polyurethanes, polycarbonates) and valorizes CO2 as a chemical feedstock. Opening up: The regioselective ring-opening of bis(α-alkylidene carbonate)s with diamines and diols is exploited to provide a broad scope of functional regioregular polymers under ambient conditions. This robust synthesis platform provides new functional variants of world-class leading polymer families (polyurethanes and polycarbonates) and valorizes CO2 as a chemical feedstock.
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Reconstitution of Low-Density Lipoproteins with Fatty Acids for the Targeted Delivery of Drugs into Cancer Cells ()
Low-density lipoproteins (LDLs) are a class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. A facile procedure is used for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts. According to a hypothesized mechanism, the reconstituted LDLs can also enable metabolism-triggered drug release while preventing the payloads from lysosomal degradation. This study demonstrates that LDLs reconstructed with fatty acids hold great promise to serve as effective and versatile nanocarriers for targeted cancer therapy. Tumor-targeting nanocarriers: The hydrophobic core of native low-density lipoproteins (LDLs) can be reconstituted with naturally occurring fatty acids (see picture). This process facilitates metabolism-triggered drug release for targeted cancer therapy.
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Integrated In Situ Characterization of a Molten Salt Catalyst Surface: Evidence of Sodium Peroxide and Hydroxyl Radical Formation ()
Sodium-based catalysts (such as Na2WO4) were proposed to selectively catalyze OH radical formation from H2O and O2 at high temperatures. This reaction may proceed on molten salt state surfaces owing to the lower melting point of the used Na salts compared to the reaction temperature. This study provides direct evidence of the molten salt state of Na2WO4, which can form OH radicals, using in situ techniques including X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), laser induced fluorescence (LIF) spectrometry, and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS). As a result, Na2O2 species, which were hypothesized to be responsible for the formation of OH radicals, have been identified on the outer surfaces at temperatures of ≥800 °C, and these species are useful for various gas-phase hydrocarbon reactions, including the selective transformation of methane to ethane. In situ characterizations at high temperature revealed that the molten state of Na2WO4 on the oxide surface produces a Na2O2-rich outer surface that catalyzes OH radical formation from an O2/H2O mixture. This process is useful for H abstraction from hydrocarbons in the gas phase.
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Long-Term Live-Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI-SiR ()
Super-resolution imaging of live cells over extended time periods with high temporal resolution requires high-density labeling and extraordinary fluorophore photostability. Herein, we achieve this goal by combining the attributes of the high-density plasma membrane probe DiI-TCO and the photostable STED dye SiR-Tz. These components undergo rapid tetrazine ligation within the plasma membrane to generate the HIDE probe DiI-SiR. Using DiI-SiR, we visualized filopodia dynamics in HeLa cells over 25 min at 0.5 s temporal resolution, and visualized dynamic contact-mediated repulsion events in primary mouse hippocampal neurons over 9 min at 2 s temporal resolution. HIDE probes such as DiI-SiR are non-toxic and do not require transfection, and their apparent photostability significantly improves the ability to monitor dynamic processes in live cells at super-resolution over biologically relevant timescales. Hiding Out: Live cells were imaged with super-resolution over extended time periods by combining the high-density plasma membrane probe DiI-TCO and the photostable STED dye SiR-Tz. These components undergo rapid tetrazine ligation within the plasma membrane to generate the high-density environment-sensitive (HIDE) probe DiI-SiR, which was used to visualize the filopodia dynamics in HeLa cells over 25 min at 0.5 s temporal resolution.
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A Molecular Boroauride: A Donor–Acceptor Complex of Anionic Gold ()
Gold is unique among the transition metals in that it is stable as an isolated anion (auride). Despite this fact, the coordination chemistry of anionic gold is virtually nonexistent, and this unique oxidation state is not readily exploited in conventional solution chemistry owing to its high reactivity. Through the use of a new molecular scaffold based on diboraanthracene (B2P2, 1), we have overcome these issues by avoiding the intermediacy of zerovalent gold and stabilizing the highly reduced gold anion through acceptor interactions. We have thus synthesized a molecular boroauride [(B2P2)Au]− ([2]−) and showed its reversible conversion between Au−I and AuI states. Through a combination of spectroscopic and computational studies, we show the neutral state to be a AuI complex with a ligand radical anion. Bonding analyses (NBO and QTAIM) and the isolobal relationship between gold and hydrogen provide support for the description of [2]− as a boroauride complex. A complex of anionic gold: Strong acceptor interactions from a diboraanthracene-diphosphine ligand enable the synthesis of a coordination complex of anionic gold (see picture). The compound can be reversibly cycled through AuI and Au−I states accommodated by geometry and redox changes at the diboraanthracene core.
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An Activatable Photosensitizer Targeted to γ-Glutamyltranspeptidase ()
We adopted a spirocyclization-based strategy to design γ-glutamyl hydroxymethyl selenorhodamine green (gGlu-HMSeR) as a photo-inactive compound that would be specifically cleaved by the tumor-associated enzyme γ-glutamyltranspeptidase (GGT) to generate the potent photosensitizer HMSeR. gGlu-HMSeR has a spirocyclic structure and is colorless and does not show marked phototoxicity toward low-GGT-expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open structure, is colored, and generates reactive oxygen species upon irradiation. The γ-glutamyl group thus serves as a tumor-targeting moiety for photodynamic therapy (PDT), switching on tumor-cell-specific phototoxicity. To validate this system, we employed chick chorioallantoic membrane (CAM), a widely used model for preliminary evaluation of drug toxicity. Photoirradiation after gGlu-HMSeR treatment resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue. Target engaged: An intramolecular spirocyclization strategy was used to design a targeted photosensitizer that is activated by γ-glutamyltranspeptidase, which is overexpressed in cancer cells. Photodynamic therapy with gGlu-HMSeR/green-light irradiation in a chick chorioallantoic membrane model resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue.
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Reentrant Structural Transitions and Collapse of Charge and Orbital Orders in Quadruple Perovskites ()
Charge and orbital degrees of freedom determine properties of many materials, and are central to many important phenomena. At high temperatures, thermal fluctuations overcome them, and high-symmetry structures are realized. On decreasing temperature, different charge- and orbital-order transitions take place accompanied by symmetry lowering. Remarkable exceptions to this general tendency, realized in Cu-doped BiMn7O12 quadruple perovskites, are presented. Introduction of Cu2+ produces mixtures of Mn3+ and Mn4+ and charge degree of freedom. BiCuMn6O12 (and compositions in the vicinity) exhibits well-defined 1:3 charge order of Mn4+ and Mn3+ and orbital order of Mn3+ near room temperature, but both charge and orbital orders collapse below about 115 K with the reentrance of the high-temperature cubic Im3‾ phase. What is interesting the collapse can be controlled by a magnetic field even without long-range magnetic order, and the collapsed phase shows nearly zero thermal expansion. Total collapse: Effects of the introduction of the charge degree of freedom into the B site of BiMn7O12 through BiCuxMn7−xO12 solid solutions are explored. BiCuMn6O12 exhibits well-defined 1:3 charge order of Mn4+ and Mn3+ and orbital order of Mn3+ near room temperature, but both charge and orbital orders collapse below about 115 K with the reentrance of the high-temperature cubic Im3‾ phase.
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Bromination of Cycloparaphenylenes: Strain-Induced Site-Selective Bis-Addition and Its Application for Late-Stage Functionalization ()
Bromination of [n]cycloparaphenylenes (CPPs) is herein reported. Small [n]CPPs (n<8) underwent a bis-bromine addition reaction with high site selectively to produce tetrabromo adducts in moderate to excellent yields. Theoretical calculations revealed that thermodynamic stability dictates both the reactivity and site selectivity of the reaction. The addition product was further converted into the octabromo product by a FeBr3-catalyzed site-selective bromination reaction. The tetra- and octabromine adducts were then transformed into mono- to tetrabromo CPPs, which were further converted into several CPP derivatives. Therefore, bromination and subsequent transformations provide a path for late-stage functionalization of CPPs. Pick a site: Small [n]CPPs (n<8) underwent a bis-bromine addition reaction with high site selectivity to produce tetrabromo adducts in moderate to excellent yields. The [5]CPP adduct was further converted into the octabromo product by a FeBr3-catalyzed site-selective bromination reaction. The tetra- and octabromine adducts were then transformed into mono- to tetrabromo CPPs, which were further converted into several CPP derivatives. FG=functional group.
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Heterogeneous Microtesla SABRE Enhancement of 15N NMR Signals ()
The hyperpolarization of heteronuclei via signal amplification by reversible exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes=1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD=cyclooctadiene] catalyst onto silica particles modified with amine linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate a circa 100-fold enhancement of 15N NMR signals in 15N-pyridine at 9.4 T following parahydrogen bubbling within a magnetic shield. No 15N NMR enhancement was observed from the supernatant liquid following catalyst separation, which along with XPS characterization supports the fact that the effects result from SABRE under heterogeneous catalytic conditions. The technique can be developed further for producing catalyst-free agents via SABRE with hyperpolarized heteronuclear spins, and thus is promising for biomedical NMR and MRI applications. Making the insensitive sensitive: A heterogeneous catalyst for NMR enhancement was prepared by immobilizing an iridium-based catalyst on silica microparticles. Addition of parahydrogen as a source of nuclear spin order within a magnetic shield led to enhancement of 15N NMR signals by about 100. The catalyst particles are easy to separate, which should allow substrates with hyperpolarized heteronuclei to be prepared free of catalyst contamination.
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Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally Simple, Rigid Linkers ()
Copper-mediated coupling between alkynes to generate a structurally rigid, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement to simultaneously maintain CuI and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from CuII-mediated oxidative damage through the formation of an insoluble CuII gel which solves the critical challenge of applying Glaser coupling to substrates that are degraded by CuII. The generality of this method is illustrated through the conjugation of a series of polar and nonpolar labels onto a fully unprotected GLP-1R agonist through a linear 7 Å diynyl linker. Diyne to meet you: A specific water-soluble bipyridine-diol (bpy-diol) ligand is shown to be optimal in the CuI-catalyzed cross-Glaser coupling of unprotected peptides and functional molecules in aqueous media. This bifunctional ligand acts to both stabilize required CuI/II species along the productive path to the desired linear 1,3-diyne linkage and sequester off-cycle peptide-degrading CuII species as an insoluble gel.
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Electrochemical Exfoliation of Layered Black Phosphorus into Phosphorene ()
Among 2D materials that recently have attracted enormous interest, black phosphorus (BP) is gaining a rising popularity due to its tunable band-gap structure, which is strongly correlated to the thickness and can enable its use in optoelectronic and electronic applications. It is therefore important to provide a facile and scalable methodology to prepare single or few-layer BP nanosheets. We propose herein a simple and fast top-down method to exfoliate a BP crystal into nanosheets of reduced thickness by using electrochemistry. The application of an anodic potential to the crystal in an acidic aqueous solution allows control over the exfoliation efficiency and quality of the nanosheets produced. X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and scanning transmission electron microscopy (STEM) have been applied to fully characterize the exfoliated material, which presented significantly reduced layer thickness compared to the starting bulk material. A layered approach: A simple and fast top-down electrochemical method for exfoliating a BP crystal into nanosheets of reduced thickness is proposed. The application of an anodic potential to the crystal in an acidic solution allows control over the exfoliation efficiency and quality of the nanosheets produced.
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Peptide-Directed Binding for the Discovery of Modulators of α-Helix-Mediated Protein–Protein Interactions: Proof-of-Concept Studies with the Apoptosis Regulator Mcl-1 ()
Targeting PPIs with small molecules can be challenging owing to large, hydrophobic binding surfaces. Herein, we describe a strategy that exploits selective α-helical PPIs, transferring these characteristics to small molecules. The proof of concept is demonstrated with the apoptosis regulator Mcl-1, commonly exploited by cancers to avoid cell death. Peptide-directed binding uses few synthetic transformations, requires the production of a small number of compounds, and generates a high percentage of hits. In this example, about 50 % of the small molecules prepared showed an IC50 value of less than 100 μm, and approximately 25 % had IC50 values below 1 μm to Mcl-1. Compounds show selectivity for Mcl-1 over other anti-apoptotic proteins, possess cytotoxicity to cancer cell lines, and induce hallmarks of apoptosis. This approach represents a novel and economic process for the rapid discovery of new α-helical PPI modulators. Selective α-helical protein–protein interactions were exploited to develop small-molecule inhibitors of these interactions. Proof-of-concept studies were conducted with the apoptosis regulator Mcl-1, and compounds that show selectivity for Mcl-1 over other anti-apoptotic proteins, are cytotoxic to cancer cell lines, and induce hallmarks of apoptosis were thus identified.
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Controlling Regioselectivity in the Enantioselective N-Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc-ProPhenol ()
The enantioselective N-alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc-ProPhenol dinuclear complex under mild conditions to afford N-alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N-alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N-alkylation products will open new windows for asymmetric catalysis and medicinal chemistry. Enantioselective N-alkylations of indole and its derivatives with aldimines are efficiently catalyzed by a zinc-ProPhenol dinuclear complex under mild conditions to afford N-alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N-alkylation products.
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Intrinsic Photoprotective Mechanisms in Chlorophylls ()
Photosynthetic energy conversion competes with the formation of chlorophyll triplet states and the generation of reactive oxygen species. These may, especially under high light stress, damage the photosynthetic apparatus. Many sophisticated photoprotective mechanisms have evolved to secure a harmless flow of excitation energy through the photosynthetic complexes. Time-resolved laser-induced optoacoustic spectroscopy was used to compare the properties of the T1 states of pheophytin a and its metallocomplexes. The lowest quantum yield of the T1 state is always observed in the Mg complex, which also shows the least efficient energy transfer to O2. Axial coordination to the central Mg further lowers the yield of both T1 and singlet oxygen. These results reveal the existence of intrinsic photoprotective mechanisms in chlorophylls, embedded in their molecular design, which substantially suppress the formation of triplet states and the efficiency of energy transfer to O2, each by 20–25 %. Such intrinsic photoprotective effects must have created a large evolutionary advantage for the Mg complexes during their evolution as the principal photoactive cofactors of photosynthetic proteins. Time-resolved laser-induced optoacoustic spectroscopy was used to compare the properties of the T1 states of pheophytin a and its metallocomplexes. The lowest quantum yield of the T1 state is always observed in the Mg complex, which also shows the least efficient energy transfer to O2. Axial coordination to the central Mg further lowers the yield of both T1 and singlet oxygen. This justifies why chlorophyll a is the principal photosynthetic pigment on Earth.
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Self-Healable Organogel Nanocomposite with Angle-Independent Structural Colors ()
Structural colors have profound implications in the fields of pigments, displays and sensors, but none of the current non-iridescent photonic materials can restore their functions after mechanical damage. Herein, we report the first self-healable organogel nanocomposites with angle-independent structural colors. The organogel nanocomposites were prepared through the co-assembly of oleophilic silica nanoparticles, silicone-based supramolecular gels, and carbon black. The organogel system enables amorphous aggregation of silica nanoparticles and the angle-independent structural colors in the nanocomposites. Moreover, the hydrogen bonding in the supramolecular gel provides self-healing ability to the system, and the structural colored films obtained could heal themselves in tens of seconds to restore storage modulus, structural color, and surface slipperiness from mechanical cuts or shear failure repeatedly. Colors, the director′s cut: Organogel nanocomposites capable of fast self-healing are prepared. The gels can form films that have angle-independent structural colors and are water-repellant, properties that are restored on self-healing.
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Opening a Can of Worm(-like Micelle)s: The Effect of Temperature of Solutions of Functionalized Dipeptides ()
A simple heat/cool cycle can be used to significantly affect the properties of a solution of a low-molecular-weight gelator at high pH. The viscosity and extensional viscosity are increased markedly, leading to materials with very different properties than when the native solution is used. Worm-like micelles: A simple heat and cool cycle was used to alter the properties of a solution containing a low-molecular-weight gelator at high pH. The viscosity and extensional viscosity increased markedly, leading to materials with very different properties than that of the native solution.
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An Electrochemical Biosensor with Dual Signal Outputs: Toward Simultaneous Quantification of pH and O2 in the Brain upon Ischemia and in a Tumor during Cancer Starvation Therapy ()
Herein, we develop a novel method for designing electrochemical biosensors with both current and potential signal outputs for the simultaneous determination of two species in a living system. Oxygen (O2) and pH, simple and very important species, are employed as model molecules. By designing and synthesizing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous detection and ratiometric quantification of O2 and pH in the brain. The reduction peak current of the hemin group increases with the concentration of O2 from 1.3 to 200.6 μm. Meanwhile, the peak potential positively shifts with decreasing pH from 8.0 to 5.5, resulting in the simultaneous determination of O2 and pH. The Fc group can serve as an internal reference for ratiometric biosensing because its current and potential signals remain almost constant with variations of O2 and pH. The developed biosensor has high temporal and spatial resolutions, as well as remarkable selectivity and accuracy, and is successfully applied in the real-time quantification of O2 and pH in the brain upon ischemia, as well as in tumor during cancer therapy. Two birds with one stone: A novel method for designing electrochemical biosensors by monitoring both current and potential signal outputs is presented. The molecule Hemin-Fc was designed for the simultaneous detection and ratiometric quantification of O2 and pH and was successfully applied to the real-time quantification in the rat brain upon ischemia and in tumor during cancer starvation therapy.
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Trifluoroacetic Anhydride Promoted Copper(I)-Catalyzed Interrupted Click Reaction: From 1,2,3-Triazoles to 3-Trifluoromethyl-Substituted 1,2,4-Triazinones ()
A copper(I)-catalyzed interrupted click reaction in the presence of trifluoroacetic anhydride has been developed, wherein an N-trifluoroacetyl group is used to accelerate the ring-opening of the putative 5-copper(I) triazolide intermediate. Under the optimized reaction conditions, a broad range of azides and alkynes were found to participate in this transformation, thus affording 3-trifluoromethyl-substituted 1,2,4-triazinones in moderate to excellent yields. The reaction has proven to be compatible with a variety of electron-withdrawing and electron–donating groups, halogens, and nitrogen- and sulfur-containing heterocycles, as well as pharmaceutically relevant molecules. Quick, not dirty: 3-Trifluoromethyl-substituted 1,2,4-triazinones are obtained from copper(I)-catalyzed interrupted click reactions of azides, alkynes, and trifluoroacetic anhydride. This cycloaddition reaction proceeds under mild reaction conditions, exhibits good tolerance of a broad range of functional groups, and provides a direct approach for the synthesis of valuable trifluoromethyl-substituted triazinones from inexpensive starting materials.
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A Fairly Stable Crystalline Silanone ()
Silanones 2 substituted by bulky amino- and phosphonium ylide substituents have been synthesized and isolated in crystalline form. Thanks to the steric protection and the strong electron-donating ability of the substituents, silanones 2 are persistent and only slowly dimerizes at room temperature (t1/2=0.5 or 5 h). Structural and theoretical analysis of 2 indicate a short Si=O bond (1.533 Å) and an enhanced polarization toward the O atom compared to Me2Si=O owing to the strong π-electron donation from the phosphonium ylide substituent. Stabilizers for silanones: Silanones substituted by bulky amino and (phosphonium)ylide substituents have been synthesized and isolated in crystalline form. Thanks to the steric protection and the strong electron-donating ability of the substituents, these silanones are persistent and only slowly dimerize at room temperature (t1/2=0.5 or 5 h).
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Synthesis of WOn-WX2 (n=2.7, 2.9; X=S, Se) Heterostructures for Highly Efficient Green Quantum Dot Light-Emitting Diodes ()
Preparation of two-dimensional (2D) heterostructures is important not only fundamentally, but also technologically for applications in electronics and optoelectronics. Herein, we report a facile colloidal method for the synthesis of WOn-WX2 (n=2.7, 2.9; X=S, Se) heterostructures by sulfurization or selenization of WOn nanomaterials. The WOn-WX2 heterostructures are composed of WO2.9 nanoparticles (NPs) or WO2.7 nanowires (NWs) grown together with single- or few-layer WX2 nanosheets (NSs). As a proof-of-concept application, the WOn-WX2 heterostructures are used as the anode interfacial buffer layer for green quantum dot light-emitting diodes (QLEDs). The QLED prepared with WO2.9 NP-WSe2 NS heterostructures achieves external quantum efficiency (EQE) of 8.53 %. To our knowledge, this is the highest efficiency in the reported green QLEDs using inorganic materials as the hole injection layer. Sulfur green: Sulfurization or selenization of WOn nanomaterials gives WOn-WX2 (n=2.7, 2.9; X=S, Se) heterostructures. Highly efficient green quantum dot light-emitting diodes (QLEDs) have been prepared by using the as-prepared WOn-WX2 heterostructures as the hole-injection layer.
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Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing ()
The reductive aminase from Aspergillus oryzae (AspRedAm) was combined with a single alcohol dehydrogenase (either metagenomic ADH-150, an ADH from Sphingobium yanoikuyae (SyADH), or a variant of the ADH from Thermoanaerobacter ethanolicus (TeSADH W110A)) in a redox-neutral cascade for the biocatalytic alkylation of amines using primary and secondary alcohols. Aliphatic and aromatic secondary amines were obtained in up to 99 % conversion, as well as chiral amines directly from the racemic alcohol precursors in up to >97 % ee, releasing water as the only byproduct. It takes two: The reductive aminase from Aspergillus oryzae (AspRedAm) was combined with a single alcohol dehydrogenase (ADH; ADH-150, SyADH or TeSADH W110A) in a redox-neutral cascade for the biocatalytic alkylation of amines using primary and secondary alcohols. Aliphatic and aromatic secondary amines were obtained in up to 99 % conversion, and chiral amines were obtained directly from the racemic alcohol precursors, releasing water as the only byproduct.
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Crystalline Diuranium Phosphinidiide and μ-Phosphido Complexes with Symmetric and Asymmetric UPU Cores ()
Reaction of [U(TrenTIPS)(PH2)] (1, TrenTIPS=N(CH2CH2NSiPri3)3) with C6H5CH2K and [U(TrenTIPS)(THF)][BPh4] (2) afforded a rare diuranium parent phosphinidiide complex [{U(TrenTIPS)}2(μ-PH)] (3). Treatment of 3 with C6H5CH2K and two equivalents of benzo-15-crown-5 ether (B15C5) gave the diuranium μ-phosphido complex [{U(TrenTIPS)}2(μ-P)][K(B15C5)2] (4). Alternatively, reaction of [U(TrenTIPS)(PH)][Na(12C4)2] (5, 12C4=12-crown-4 ether) with [U{N(CH2CH2NSiMe2But)2CH2CH2NSi(Me)(CH2)(But)}] (6) produced the diuranium μ-phosphido complex [{U(TrenTIPS)}(μ-P){U(TrenDMBS)}][Na(12C4)2] [7, TrenDMBS=N(CH2CH2NSiMe2But)3]. Compounds 4 and 7 are unprecedented examples of uranium phosphido complexes outside of matrix isolation studies, and they rapidly decompose in solution underscoring the paucity of uranium phosphido complexes. Interestingly, 4 and 7 feature symmetric and asymmetric UPU cores, respectively, reflecting their differing steric profiles. Outside the matrix: Prepared by two different routes, the first examples of uranium phosphido complexes outside of cryogenic matrix isolation conditions are reported, revealing symmetric and asymmetric (shown; U green, P purple, N blue, Si yellow) UPU cores in the solid-state crystal structures.
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Towards a Comprehensive Understanding of the Reaction Mechanisms Between Defective MoS2 and Thiol Molecules ()
Sulfur vacancies (SVs) inherent in MoS2 are generally detrimental for carrier mobility and optical properties. Thiol chemistry has been explored for SV repair and surface functionalization. However, the resultant products and reaction mechanisms are still controversial. Herein, a comprehensive understanding on the reactions is provided by tracking potential energy surfaces and kinetic studies. The reactions are dominated by two competitive mechanisms that lead to either functionalization products or repair SVs, and the polarization effect from decorating thiol molecules and thermal effect are two determining factors. Electron-donating groups are conducive to the repairing reaction whereas electron-withdrawing groups facilitate the functionalization process. Moreover, the predominant reaction mechanism can be switched by increasing the temperature. This study fosters a way of precisely tailoring the electronic and optical properties of MoS2 by means of thiol chemistry approaches. Sulfur vacancies (SVs) inherent in MoS2 are generally detrimental for carrier mobility and optical properties. Thiols have been investigated for SV repair and surface functionalization. Electron-donating groups on thiols support repair whereas electron-withdrawing groups facilitate functionalization. The predominant reaction can also be switched by increasing the temperature.
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From a Molecular 2Fe-2Se Precursor to a Highly Efficient Iron Diselenide Electrocatalyst for Overall Water Splitting ()
A highly active FeSe2 electrocatalyst for durable overall water splitting was prepared from a molecular 2Fe-2Se precursor. The as-synthesized FeSe2 was electrophoretically deposited on nickel foam and applied to the oxygen and hydrogen evolution reactions (OER and HER, respectively) in alkaline media. When used as an oxygen-evolution electrode, a low 245 mV overpotential was achieved at a current density of 10 mA cm−2, representing outstanding catalytic activity and stability because of Fe(OH)2/FeOOH active sites formed at the surface of FeSe2. Remarkably, the system is also favorable for the HER. Moreover, an overall water-splitting setup was fabricated using a two-electrode cell, which displayed a low cell voltage and high stability. In summary, the first iron selenide material is reported that can be used as a bifunctional electrocatalyst for the OER and HER, as well as overall water splitting. Bridging the gap: A highly active iron diselenide electrocatalyst was prepared at low temperature from a bioinspired 2Fe-2Se molecular complex (Dep = diethylphenyl). The catalyst was applied to bifunctional oxygen and hydrogen evolution reactions, as well as overall water splitting. The nature of active sites and structure–activity relationships of the electrocatalyst were uncovered.
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Lateral Organization of Host Heterogeneous Raft-like Membranes Altered by the Myristoyl Modification of Tyrosine Kinase c-Src ()
Membrane-bound c-Src non-receptor tyrosine kinase, unlike other acyl-modified lipid-anchored proteins, anchors to the membrane by a myristoyl chain along with a polybasic residue stretch, which is shorter in chain length than its host membrane. The packing defect arising from this mismatched chain length of the host and the lipid anchor significantly affects the lateral organization of heterogeneous membranes. We reveal the mixing of phase domains and formation of novel nanoscale-clusters upon membrane binding of the Myr-Src (2–9) peptide. Fluorescence cross correlation spectroscopy was used to explore the nature of these clusters. We show that Myr-Src (2–9) is able to oligomerize, and the peptide clusters are embedded in a lipid platform generated by lipid sorting. Further, using confocal fluorescence microscopy and FRET assays we show that localized charge enrichment and membrane curvature are able to shift the partition coefficient towards the more ordered lipid phase. Lipid–protein nanoclusters: Tyrosine kinase c-Src attaches to the plasma membrane using a myristoyl (Myr) anchor that is shorter than the surrounding lipid matrix. Insertion of lipidated anchor of Myr-Src into various model biomembranes alters the nanoscale organization of the peptide upon membrane binding and leads to an altered lateral structure of the host membrane.
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Living and Conducting: Coating Individual Bacterial Cells with In Situ Formed Polypyrrole ()
Coating individual bacterial cells with conjugated polymers to endow them with more functionalities is highly desirable. Here, we developed an in situ polymerization method to coat polypyrrole on the surface of individual Shewanella oneidensis MR-1, Escherichia coli, Ochrobacterium anthropic or Streptococcus thermophilus. All of these as-coated cells from different bacterial species displayed enhanced conductivities without affecting viability, suggesting the generality of our coating method. Because of their excellent conductivity, we employed polypyrrole-coated Shewanella oneidensis MR-1 as an anode in microbial fuel cells (MFCs) and found that not only direct contact-based extracellular electron transfer is dramatically enhanced, but also the viability of bacterial cells in MFCs is improved. Our results indicate that coating individual bacteria with conjugated polymers could be a promising strategy to enhance their performance or enrich them with more functionalities. Surface modification of bacteria: The surface of individual bacterial cells was in situ coated by polypyrrole as a conductive layer to endow bacteria with enhanced electrical conductivity. The PPy coatings promote the contact-based electron transfer between S. oneidensis MR-1 and the electrode, leading to a huge improvement in the bioelectricity generation of microbial fuel cells (MFCs).
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γ-Functionalizations of Amines through Visible-Light-Mediated, Redox-Neutral C−C Bond Cleavage ()
Cleavage of unstrained C−C bonds under mild, redox-neutral conditions represents a challenging endeavor which is accomplished here in the context of a flexible, visible-light-mediated, γ-functionalization of amines. In situ generated C-centered radicals are harvested in the presence of Michael acceptors, thiols and alkyl halides to efficiently form new C(sp3)−C(sp3), C(sp3)−H and C(sp3)−Br bonds, respectively. Visible light enables the facile cleavage of unstrained C−C bonds and the subsequent remote functionalization of in situ generated C-centered radicals in γ-position to amino groups. In the presence of Michael acceptors, thiols, or alkyl halides, new C(sp3)−C(sp3), C(sp3)−H, and C(sp3)−Br bonds are efficiently formed.
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A Direct Synthesis of Highly Substituted π-Rich Aromatic Heterocycles from Oxetanes ()
The ubiquitous use of π-rich five-membered heterocycles has driven the development of new methods for their synthesis for more than a century. Here, we disclose a general and reliable reaction manifold for the construction of highly substituted heterocycles through a facile Lewis-acid-catalyzed oxetane rearrangement. Notably, this methodology employs a keto-oxetane motif as a 1,4-dicarbonyl surrogate, which can be synthesized using robust alkylation or alkenylation reactions, and thus obviates the need to access 1,4-dicarbonyl compounds via umpoled starting materials. We harnessed this reactivity to generate a broad range of substituted furans and pyrroles, and extended this methodology to produce benzo-fused versions thereof. Upon alkenylation or addition to the keto function of inexpensive 3-oxetanone, the strained oxetane ring is poised for a facile and general rearrangement to make important heterocycles.
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Practical Alkoxythiocarbonyl Auxiliaries for Iridium(I)-Catalyzed C−H Alkylation of Azacycles ()
The development of new and practical 3-pentoxythiocarbonyl auxiliaries for IrI-catalyzed C−H alkylation of azacycles is described. This method allows for the α-C−H alkylation of a variety of substituted pyrrolidines, piperidines, and tetrahydroisoquinolines through alkylation with alkenes. While the practicality of these simple carbamate-type auxiliaries is underscored by the ease of installation and removal, the method's utility is demonstrated in its ability to functionalize biologically relevant l-proline and l-trans-hydroxyproline, delivering unique 2,5-dialkylated amino acid analogues that are not accessible by other C−H functionalization methods. Fine-tuning: A carbamate-type 3-pentoxythiocarbonyl auxiliary has been developed for the α-C−H alkylation of a variety of substituted N-heterocycles through reaction with alkenes (see scheme). Application to biologically relevant l-proline and l-trans-hydroxyproline delivered unique 2,5-dialkylated amino acid analogues.
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Enantioselective Oxidative (4+3) Cycloadditions between Allenamides and Furans through Bifunctional Hydrogen-Bonding/Ion-Pairing Interactions ()
BINOL-based N-trifluoromethanesulfonyl phosphoramides catalyze the enantioselective (4+3) cycloaddition between furans and oxyallyl cations, the latter being generated in situ by oxidation of allenamides. The chiral organic phosphoramide counteranion is proposed to engage in the activation of the oxyallyl cation intermediate through cooperative hydrogen-bonding and ion-pairing interactions, enabling an efficient chirality transfer that provide the final adducts with high diastereo- and enantioselectivities. Remarkably, the reaction shows a wide substrate scope that includes a variety of substituted allenamides and furans. Opposite charges attract: In situ generated oxyallyl cations react with a variety of furans in the presence of a BINOL-based N-sulfonyl phosphoramide catalyst, furnishing (4+3) cycloaddition products in excellent yields and with high stereocontrol. The reaction is enabled by bifunctional activation of the oxyallyl cation by hydrogen bonding in combination with the formation of a tightly bound ion pair.
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Silver-Catalyzed Oxidative C(sp3)−P Bond Formation through C−C and P−H Bond Cleavage ()
The silver-catalyzed oxidative C(sp3)−H/P−H cross-coupling of 1,3-dicarbonyl compounds with H-phosphonates, followed by a chemo- and regioselective C(sp3)−C(CO) bond-cleavage step, provided heavily functionalized β-ketophosphonates. This novel method based on a readily available reaction system exhibits wide scope, high functional-group tolerance, and exclusive selectivity. A silver trigger: A wide range of β-ketophosphonates were synthesized readily by a silver-catalyzed transformation involving the oxidative C(sp3)−H/ P−H cross-coupling of 1,3-dicarbonyl compounds with H-phosphonates and tandem exclusive C(sp3)−C(CO) bond cleavage (see scheme). The base-, ligand-, and additive-free procedure has the additional advantages of a simple catalyst system and good functional-group tolerance.
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Iridium-Catalyzed Enantioselective Synthesis of Pyrrole-Annulated Medium-Sized-Ring Compounds ()
Enantioselective synthesis of pyrrole-annulated medium-sized-ring compounds by an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis sequence is presented. Various substituted pyrrole-annulated seven- and eight-membered-ring products were obtained under mild reaction conditions with moderate to good yields and excellent enantioselectivity. Additionally, these products contain a scaffold widely distributed in natural products and biologically active compounds. The current method provides a convenient way for accessing such pyrrole-anuulated medium-sized-ring compounds. Life without ‘pyrrole': Enantioselective synthesis of pyrrole-annulated medium-sized-ring compounds by an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis sequence is presented. Various substituted pyrrole-annulated seven- and eight-membered-ring products were obtained under mild reaction conditions with moderate to good yields and excellent enantioselectivity.
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Exceptionally Strong Electron-Donating Ability of Bora-Ylide Substituent vis-à-vis Silylene and Silylium Ion ()
Electropositive boron-based substituent (phosphonium bora-ylide) with an exceptionally strong π- and σ-electron donating character dramatically increases the stability of a new type of N-heterocyclic silylene 2 featuring amino- and bora-ylide-substituents. Moreover, the related silylium ion 4 and transition-metal–silylene complexes, with trigonal-planar geometries around the silicon center, are also well stabilized. Therefore, the N,B-heterocyclic silylene 2 can be used as a strongly electron-donating innocent ligand in coordination chemistry similarly to N-heterocyclic carbenes. Electron-donating ligand: An electropositive boron-based substituent (phosphonium bora-ylide) with an exceptionally strong π- and σ-electron donating character increases the stability of a new type of N-heterocyclic silylene featuring amino and bora-ylide substituents. It also efficiently stabilizes the related silylium ion and transition-metal–silylene complexes even with a trigonal-planar geometry around the silicon center.
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Copper-Catalyzed Three-Component Carboazidation of Alkenes with Acetonitrile and Sodium Azide ()
A copper-catalyzed three-component reaction of alkenes, acetonitrile, and sodium azide afforded γ-azido alkyl nitriles by formation of one C(sp3)−C(sp3) bond and one C(sp3)−N bond. The transformation allows concomitant introduction of two highly versatile groups (CN and N3) across the double bond. A sequence involving the copper-mediated generation of a cyanomethyl radical and its subsequent addition to an alkene, and a C(sp3)−N bond formation accounted for the reaction outcome. The resulting γ-azido alkyl nitrile can be easily converted into 1,4-diamines, γ-amino nitriles, γ-azido esters, and γ-lactams of significant synthetic value. Be disciplined: Regioselective azidocyanomethylation of alkenes takes place smoothly in the presence of di-tert-butyl peroxide (DTBP), a catalytic amount of Cu(OAc)2, and MnF3 to afford γ-azido alkylnitriles, which are highly valued synthetic building blocks. The reaction involves the copper-mediated generation of a cyanomethyl radical and its subsequent addition to an alkene, and a C(sp3)−N bond formation.
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Delineating the Mechanism of Ionic Liquids in the Synthesis of Quinazoline-2,4(1H,3H)-dione from 2-Aminobenzonitrile and CO2 ()
Ionic liquids (ILs) are versatile solvents and catalysts for the synthesis of quinazoline-2,4-dione from 2-aminobenzonitrile and CO2. However, the role of the IL in this reaction is poorly understood. Consequently, we investigated this reaction and showed that the IL cation does not play a significant role in the activation of the substrates, and instead plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pKa of the IL anion (conjugate acid) and the reaction rate was identified with maximum catalyst efficiency observed at a pKa of >14.7 in DMSO. The base-catalyzed reaction is limited by the acidity of the quinazoline-2,4-dione product, which is deprotonated by more basic catalysts, leading to the formation of the quinazolide anion (conjugate acid pKa 14.7). Neutralization of the original catalyst and formation of the quinazolide anion catalyst leads to the observed reaction limit. The ionic liquid (IL) cation does not play a significant role in the activation of the substrates in the synthesis of quinazoline-2,4-dione from 2-aminobenzonitrile and CO2. Instead, it plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pKa of the IL anion (conjugate acid) and the reaction rate was identified, with maximum catalyst efficiency observed at a pKa of >14.7 in DMSO.
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Hydroformylation of Alkenes in a Planetary Ball Mill: From Additive-Controlled Reactivity to Supramolecular Control of Regioselectivity ()
The Rh-catalyzed hydroformylation of aromatic-substituted alkenes is performed in a planetary ball mill under CO/H2 pressure. The dispersion of the substrate molecules and the Rh-catalyst into the grinding jar is ensured by saccharides: methyl-α-d-glucopyranoside, acyclic dextrins, or cyclodextrins (CDs, cyclic oligosaccharides). The reaction affords the exclusive formation of aldehydes whatever the saccharide. Acyclic saccharides disperse the components within the solid mixture leading to high conversions of alkenes. However, they showed typical selectivity for α-aldehyde products. If CDs are the dispersing additive, the steric hindrance exerted by the CDs on the primary coordination sphere of the metal modifies the selectivity so that the β-aldehydes were also formed in non-negligible proportions. Such through-space control via hydrophobic effects over reactivity and regioselectivity reveals the potential of such solventless process for catalysis in solid state. Ground sugar: The rhodium-catalyzed hydroformylation of aromatic-substituted alkenes is efficiently performed in a planetary ball mill under CO/H2 pressure. It gives aldehydes in high chemoselectivity and with modification of the regioselectivity to the less-preferred β-aldehydes.
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Mechanistic Insight Leads to a Ligand Which Facilitates the Palladium-Catalyzed Formation of 2-(Hetero)Arylaminooxazoles and 4-(Hetero)Arylaminothiazoles ()
By using mechanistic insight, a new ligand (EPhos) for the palladium-catalyzed C−N cross-coupling between primary amines and aryl halides has been developed. Employing an isopropoxy group at the C3-position favors the C-bound isomer of the ligand-supported palladium(II) complexes and leads to significantly improved reactivity. The use of a catalyst system based on EPhos with NaOPh as a mild homogeneous base proved to be very effective in the formation of 4-arylaminothiazoles and highly functionalized 2-arylaminooxazoles. Previously, these were not readily accessible using palladium catalysis. Cross-examination: A new ligand, EPhos, for palladium-catalyzed C−N cross-couplings has been developed based on a structure–activity relationship of BrettPhos-related ligands. EPhos was successfully applied in the Pd-catalyzed formation of 2-(hetero)arylaminooxazoles and 4-(hetero)arylaminothiazoles, the synthesis of which had previously proven problematic in transition-metal catalysis.
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Enantioselective Organocatalytic Intramolecular Aza-Diels–Alder Reaction ()
A highly efficient catalytic enantioselective intramolecular Povarov reaction was developed with primary anilines as 2-azadiene precursors. A wide variety of angularly fused azacycles were obtained without column chromatography in high to excellent yields and with excellent diastereo- and enantioselectivity (d.r.>99:1 and up to e.r. 99:1). Furthermore, the catalyst loading could be lowered to 1 mol %, and the obtained azacycles could be used as key intermediates for further transformations to generate additional molecular diversity. A match made in heaven: A matching effect between a chiral phosphoric acid and cycloadduct precursors enabled the development of an enantioselective intramolecular Povarov reaction (see scheme). The efficient reaction is broad in scope and proceeded with high diastereo- and enantioselectivity. Simple precipitation was sufficient for the isolation of each product in excellent purity and without the need for chromatographic separation.
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Ta(CNDipp)6: An Isocyanide Analogue of Hexacarbonyltantalum(0) ()
Hexakis(2,6-diisopropylphenylisocyanide)tantalum is the first isocyanide analogue of the highly unstable Ta(CO)6 and represents the only well-defined zerovalent tantalum complex to be prepared by conventional laboratory methods. Two prior examples of homoleptic Ta0 complexes are known, Ta(benzene)2 and Ta(dmpe)3, dmpe=1,2-bis(dimethylphosphano)ethane, but these have only been accessed via ligand co-condensation with tantalum vapor in a sophisticated metal-atom reactor. Consistent with its 17-electron nature, Ta(CNDipp)6 undergoes facile one-electron oxidation, reduction, or disproportionation reactions. In this sense, it qualitatively resembles V(CO)6, the only paramagnetic homoleptic metal carbonyl isolable under ambient conditions. Ta tantalizing: The first paramagnetic homoleptic metal isocyanide of a 5d-transition metal is hexakis(2,6-diisopropylphenylisocyanide)tantalum. It is an analogue of the highly unstable hexacarbonyltantalum(0) and is the only structurally authenticated zerovalent tantalum complex to be prepared by conventional laboratory methods. It has properties consistent with a 17-electron metalloradical.
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Iron-Catalyzed Intramolecular Aminations of C(sp3)−H Bonds in Alkylaryl Azides ()
The nucleophilic iron complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) catalyzes the direct intramolecular amination of unactivated C(sp3)−H bonds in alkylaryl azides, which results in the formation of substituted indoline and tetrahydroquinoline derivatives. What a surprise: The anionic iron complex Bu4N[Fe(CO)3(NO)] catalyzes the denitrogenative C(sp3)−H amination of a variety of alkylaryl azides to the corresponding indolines and, unexpectedly, tetrahydroquinolines in good yields.
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Reactions of Donor–Acceptor Cyclopropanes with Naphthoquinones: Redox and Lewis Acid Catalysis Working in Concert ()
Reactions of 2-arylcyclopropane dicarboxylates with naphthoquinones are reported. The key feature was the use of catalytic amounts of SnCl2, which acts as both an electron donor and a Lewis acid. By an in situ umpolung of naphthoquinone the formerly electrophilic species is converted into a nucleophile that is able to trigger the ring-opening of the three-membered ring with formation of a new C−C bond. Treatment of these products with base under oxidative conditions resulted—through loss of methyl formate—in cyclopentannulated products with fully conjugated π systems exhibiting intensive absorptions in the visible range. Electron power: Electrophilic naphthoquinone is converted by a catalytic amount of tin(II) into the corresponding nucleophilic species, which is able to open donor–acceptor cyclopropanes. Basic oxidative conditions lead to a [3+2]-cyclopentannulation resulting in a completely conjugated π system.
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Tight Molecular Recognition of Benzo[a]pyrene by a High-Affinity Antibody ()
Benzo[a]pyrene, which is produced during the incomplete combustion of organic material, is an abundant noxious pollutant because of its carcinogenic metabolic degradation products. The high-affinity (KD≈3 nm) monoclonal antibody 22F12 allows facile bioanalytical quantification of benzo[a]pyrene even in complex matrices. We report the functional and X-ray crystallographic analysis of 22F12 in complex with 3-hydroxybenzo[a]pyrene after cloning of the V-genes and production as a recombinant Fab fragment. The polycyclic aromatic hydrocarbon is bound in a deep pocket between the light and heavy chains, surrounded mainly by aromatic and aliphatic amino acid side chains. Interestingly, the hapten–antibody interface is less densely packed than expected and reveals polar, H-bond-like interactions with the polycyclic aromatic π-electron system, which may allow the antibody to maintain a large, predominantly hydrophobic binding site in an aqueous environment while providing sufficient complementarity to its ligand. Threat uncovered: Molecular recognition of (hydroxylated) benzo[a]pyrene was achieved through development of the high-affinity antibody 22F12, an immunochemical reagent that allows sensitive bioanalytical quantification of noxious polycyclic aromatic hydrocarbons even in complex matrices.
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Opto-electrochemical In Situ Monitoring of the Cathodic Formation of Single Cobalt Nanoparticles ()
Single-particle electrochemistry at a nanoelectrode is explored by dark-field optical microscopy. The analysis of the scattered light allows in situ dynamic monitoring of the electrodeposition of single cobalt nanoparticles down to a radius of 65 nm. Larger sub-micrometer particles are directly sized optically by super-localization of the edges and the scattered light contains complementary information concerning the particle redox chemistry. This opto-electrochemical approach is used to derive mechanistic insights about electrocatalysis that are not accessible from single-particle electrochemistry. Single-particle electrochemistry at a nanoelectrode can be explored by dark-field optical microscopy. The analysis of the scattered light makes it possible to monitor the electrodeposition of single cobalt nanoparticles in situ down to a radius of 65 nm. The scattered light also contains information used to derive mechanistic insights not accessible from single-particle electrochemistry.
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Covalently Interlocked Cyclohexa-m-phenylenes and Their Assembly: En Route to Supramolecular 3D Carbon Nanostructures ()
In our search to cluster as many phenylene units as possible in a given space, we have proceeded to the three-dimensional world of benzene-based molecules by employing covalently interlocked cyclohexa-m-phenylenes, as present in the unique paddlewheel-shaped polyphenylene 10. A precursor was conceived, in which freely rotating m-chlorophenylene units provide sufficient solubility along with the necessary proximity for the final ring closure to give 10. Monitoring the assembly of solubilized tert-butyl derivatives of 10 into supramolecular carbon nanostructures by dynamic light scattering (DLS) and Brillouin light scattering (BLS) revealed the dimensions of the initially formed aggregates as well as the amorphous character of the solid state. Essentially strain-free and thermally stable paddlewheel polyphenylenes consisting of two covalently interlocked cyclohexa-m-phenylenes have been synthesized. Tuning of the solubility allowed the hierarchical formation of three-dimensional carbon nanostructures to be monitored.
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