Angewandte Chemie International Edition

A De Novo Heterodimeric Due Ferri Protein Minimizes the Release of Reactive Intermediates in Dioxygen-dependent Oxidation ()
Metalloproteins utilize O₂ as an oxidant, and they often achieve a 4-electron reduction without H₂O₂ or oxygen radical release. Several proteins have been designed to catalyze one or two-electron oxidative chemistry, but the de novo design of a protein that catalyzes the net 4-electron reduction of O₂ has not been reported yet. We report here the construction of a diiron-binding four-helix bundle, made up of two different covalently linked α2 monomers, through click chemistry. Surprisingly, the prototype protein, DF-C1, showed a large divergence in its reactivity from earlier DFs. DFs release the quinone imine and free H₂O₂ in the oxidation of 4-aminophenol in the presence of O₂, whereas FeIII-DF-C1 sequesters the quinone imine into the active site, and catalyzes inside the scaffold an oxidative coupling between oxidized and reduced 4-aminophenol. The asymmetry of the scaffold allowed a fine-engineering of the substrate binding pocket, that ensures selectivity.
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Mimicking the 'Rose Petal' and 'Lotus Leaf' Effects on Alumina by Surface Functionalization and Metal Ion Coordination ()
Functional difference of superhydrophobic surfaces such as lotus leaf and rose petals are due to the subtle architectural features created by Nature. Mimicry of these surfaces with synthetic molecules continues to be fascinating as well as challenging. Herein, we demonstrate how the wetting property of inherently hydrophilic alumina surface can be modified with two distinct superhydrophobic behaviors. Functionalization of alumina with an organic ligand resulted in a rose petal-like surface (water pinning) with a contact angle of 145° and a high contact angle hysteresis (± 69°). Subsequent interaction of the ligand with Zn2+ resulted in a lotus leaf-like surface with water rolling behavior due to high contact angle (165°) and low contact angle hysteresis (± 2°). In both cases, coating of an aromatic bis-aldehyde attached with alkoxy chains was necessary to emulate the nanowaxy cuticular feature of natural superhydrophobic materials.
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Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic Media ()
A new Pummerer-type C-C coupling protocol is introduced based on turbo-organomagnesium amides that unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of sp3, sp2 and sp C-nucleophiles and seamlessly integrates with C-H and C-X magnesiation. Due to the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides and boronic esters through a single strategy.
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Preparation of Functionalized Diaryl- and Diheteroaryl- Lanthanum Reagents via a Fast Halogen-Lanthanum Exchange ()
nBu2LaMe allows a fast and convenient halogen-lanthanum exchange of aryl- and heteroaryl halides (X = Br, I) leading to functionalized diaryl- and diheteroaryl-lanthanum derivatives. Their subsequent trappings with selected electrophiles, such as ketones, aldehydes and amides proceeded smoothly at −50 °C in THF affording polyfunctionalized alcohols and carbonyl derivatives. Competitive kinetic measurements show a similar reactivity trend as the Br/Mg-exchange, but 10^6 faster rates making it comparable to the Br/Li-exchange.
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Catalytic Hydroalkylation of Allenes ()
We have developed a catalytic method for hydroalkylation of allenes using alkyl triflates as electrophiles and silane as a hydride source. The reaction has an excellent substrate scope and is compatible with a wide range of functional groups, including esters, aryl halides, aryl boronic esters, sulfonamides, alkyl tosylates, and alkyl bromides. We found evidence for the reaction mechanism that involves unusual dinuclear copper ally complexes as catalytic intermediates. The unusual structure of these complexes provides rationale for their unexpected reactivity.
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Recognizing Through-Bond and Through-Space Self-Exchange Charge/Spin Transfer Pathways in Bis(triarylamine) Radical Cations with Similar Geometrical Arrangements ()
Radical cations of bis(triarylamine)s, 3 and 4, in which the triarylamine redox centers are bridged by ortho-phenylene and ortho-carborane cluster, respectively, have been prepared to elucidate the difference in intramolecular charge/spin transfer (ICT/IST) pathway due to the two different bridging units affording similar geometrical arrangements between the redox centers. Electrochemistry, absorption spectroscopy, VT-ESR spectroscopy, and DFT calculations reveal that 3*+ and 4*+ are classified into class-II and class-I mixed valence systems, respectively, and therefore, through-bond and through-space mechanisms are dominant for the ICT/IST phenomena in 3*+ and 4*+, respectively. Moreover, SQUID measurements for dicationic species provides the fact that virtually no spin-exchange interaction is observed for 42+, while the intramolecular antiferromagnetic coupling between spins in 32+, in accordance with the existence of conjugation pathway for ortho-phenylene bridge.
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Multi-step crystallization of barium carbonate: rapid interconversion of amorphous and crystalline precursors ()
We report the direct observation of amorphous barium carbonate (ABC), which transforms into a previously unknown barium carbonate hydrate we call gortatowskite within a few hundred milliseconds of formation. In situ X-ray scattering, cryo-, and low-dose electron microscopy were used to capture the transformation of nanoparticulate ABC into gortatowskite crystals, highly anisotropic sheets that are up to 1 µm in width, yet only ~10 nm in thickness. Recrystallization of gortatowskite to witherite starts within 30 seconds. We describe a bulk synthesis and report a first assessment of the composition, vibrational spectra, and structure of gortotowskite. Our findings indicate that transient amorphous and crystalline precursors can play a role in aqueous precipitation pathways that may often be overlooked due to their extremely short lifetimes and small dimensions. However, such transient precursors may be integral to the formation of more stable phases.
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Interrogating membrane protein conformational dynamics within native lipid compositions ()
Membrane protein-lipid interplay is important for cellular function, however, tools enabling the interrogation of protein dynamics within native lipid environments are scarce and often invasive. We establish that the styrene-maleic acid anhydride lipid particle (SMALP) technology can be coupled with hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate membrane protein conformational dynamics within native lipid bilayers. We demonstrate changes in accessibility and dynamics of the rhomboid protease, GlpG, captured within three different native lipid compositions, and identify protein regions sensitive to changes in the native lipid environment. Our results illuminate the value of this approach for distinguishing the putative role(s) of the native lipid composition in modulating membrane protein conformational dynamics.
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Isoquinoline-1-carboxylate as a Traceless Leaving Group for Chelation-Assisted Glycosylation under Mild Neutral Conditions ()
Glycosyl Isoquinoline-1-carboxylate was developed as a novel benchtop stable and readily available glycosyl donor. The glycosylation reaction was promoted by inexpensive Cu(OTf)2 salt under very mild conditions. The copper isoquinoline-1-carboxylate salt was precipitated from the solution and rendered it as a traceless leaving group. Surprisingly, the proton from the acceptor was absorbed by the precipitated metal complex and the reaction mixture remained neutral. The copper-promoted glycosylation was also proven to be completely orthogonal to the gold-promoted glycosylation and an iterative synthesis of oligosaccharides from benchtop stable anomeric ester building blocks becomes possible under mild conditions.
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Cucurbit[7]uril as a Supramolecular Artificial Enzyme for Diels-Alder Reactions ()
The ability to mimic the activity of natural enzymes using supramolecular constructs (artificial enzymes) represents a vibrant scientific research field. Herein, we demonstrate that cucurbit[7]uril (CB[7]) can catalyze Diels-Alder reactions for a number of substituted and unreactive N-allyl-2-furfurylamines under biomimetic conditions, without the need for protecting groups, yielding powerful synthons in previously unreported mild conditions. CB[7] rearranges the substrate in a highly reactive conformation and shields it from the aqueous environment, thereby mimicking the mode of action of a natural Diels-Alderase. These findings can be directly applied to the phenomenon of product inhibition observed in natural Diels-Alderase enzymes, and pave the way toward the development of novel, supramolecular-based green catalysts.
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Azido-Functionalized 5ʹ-Cap Analogs for Preparation of Translationally Active mRNAs Suitable for Fluorescent Labeling in Living Cells ()
The 7-methylguanosine (m7G) cap structure is a unique feature present at the 5ʹ ends of messenger RNAs (mRNAs) that can be subjected to extensive modifications, resulting in alterations to mRNA properties (e.g. translability, susceptibility to degradation). It also can provide molecular tools to study mRNA metabolism. Here, we developed new mRNA 5ʹ cap-based tools that enable the site-specific labeling of RNA at the 5ʹ end using strain-promoted azide-alkyne cycloaddition (SPAAC), i.e. bioorthogonal, copper-free click chemistry, and support the mRNA's basic function in protein biosynthesis. Some of these azide-functionalized compounds are equipped with additional modifications to augment mRNA properties. The application of these tools was demonstrated by labeling translationally active mRNAs in living cells.
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Controllable modular growth of hierarchical MOF-on-MOF architectures ()
Fabrication of hybrid MOF-on-MOF heteroarchitectures can create novel and multifunctional platforms to achieve desired properties. However, only MOFs with similar crystallographic parameters can be hybridized by the classical epitaxial growth method (EGM), which largely suppressed its applications. Herein, we demonstrated a general strategy called internal extended growth method (IEGM) for the feasible assembly of MOFs with distinct crystallographic parameters in an MOF matrix. Various MOFs with diverse functions could be introduced in a modular MOF matrix to form 3D core-satellite pluralistic hybrid system. Additionally, the number of different MOF crystals interspersed could be variable on demand. More importantly, the different MOF crystals distributed in individual domains could be used to further incorporate functional units or enhance target functions.
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The First Boron-Tellurium Double Bond: Direct Insertion of Heavy Chalcogens into a Mn=B Double Bond ()
The base-stabilized borylene [Cp(OC)2Mn=BtBu(IMe)] readily reacts with elemental chalcogens in an insertion reaction that yields borachalcone complexes [(OC)2Mn-E=BtBu(IMe)] (E = S, Se, Te). The tellurium example features the first double bond between boron and tellurium, making Te the heaviest main-group element to make multiple bonds with boron. This unprecedented interaction has been fully investigated experimentally and computationally.
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One-pot four-segment ligation realized by selenoester and its application to the synthesis of superoxide dismutase ()
The synthesis of the peptide selenoester was efficiently carried out by the 9-fluorenylmethoxycarbonyl method using the N-alkylcysteine at the C-terminus of the peptide as the N-to-S acyl shift device. The selenoester highly selectively reacted with the terminal amino group of the peptide aryl thioester in the presence of N, N-diisopropylethylamine and dipyridyldisulfide, maintaining the aryl thioester intact. Combining with the silver ion promoted and silver ion free thioester activation method, the one-pot four-segment ligation was realized. The method was successfully used to assemble the entire sequence of the superoxide dismutase (SOD) composed of 153 amino acid residues in one-pot. After the folding reaction, the fully-active SOD was obtained.
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Visible-Light-Driven Pd-Catalyzed Radical Alkylation of C─H Bonds with General Unactivated Alkyl Bromides ()
Herein, we report a novel visible-light photoredox system with Pd(PPh3)4 as the sole catalyst to realize the first direct cross-coupling of C(sp3)─H bonds in N-aryl tetrahydroisoquinolines with general unactivated alkyl bromides. Moreover, intra- and inter-molecular alkylations of hetero-arenes were also developped under mild reaction conditions. A variety of tertiary, secondary and primary alkyl bromides undergo such reactions to generate C(sp3)─C(sp3) and C(sp2)─C(sp3) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional group tolerance and facile generation of quaternary centers. Mechanistic studies indicate that the simple Pd-complex acts as the visible-light photocatalyst and radicals are involved in the process.
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A Nickel-Catalyzed Carbonyl-Heck Reaction ()
The use of transition metal catalysis to enable the coupling of readily available organic molecules has greatly enhanced the chemist's ability to access complex chemical structures. In this work, an intermolecular coupling reaction that unites organotriflates and aldehydes is presented. A unique catalyst system is identified to enable this reaction, featuring a Ni(0) precatalyst, a tridentate Triphos ligand, and a bulky amine base. This transformation provides access to a variety of ketone-containing products without the selectivity and reactivity-related challenges associated with more traditional Friedel-Crafts reactions. A Heck-type mechanism is postulated, wherein the pi-bond of the aldehyde takes the role of the olefin in the insertion/elimination steps.
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Biological Imaging with Medium-Sensitive Bichromatic Flexible Fluorescent (FlexFluor) Dyes ()
A new family of environment-sensitive shape-shifting molecules have been developed as flexible fluorescent (FlexFluor) dyes for biological imaging applications. These compounds feature a flexible bithiophene-based fluorophore that gives rise to different emission colors in lipophilic or hydrophilic environments, as well as side-groups that can be easily synthetically modified. As the first fluorescent dyes in which emission color can be used to indicate lipid/water environments, the behavior of FlexFluor dyes in different solvents has been studied, and used to simultaneously highlight lipid and water contents in adipose and brain tissues using optical fluorescence microscopy.
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Reversible Cleavage/Formation of the Cr-Cr Quintuple Bond in the Highly Regioselective Alkyne Cyclotrimerization ()
Here we report the employment of the quintuply bonded dichromium amidinates [Cr{κ2-HC(N-2,6-iPr2C6H3)(N-2,6-R2C6H3)}]2 (R = iPr (1), Me (7)) as catalysts to mediate the [2+2+2] cyclotrimerization of terminal alkynes giving 1,3,5-trisubstituted benzenes. During the catalysis, the ultrashort Cr-Cr quintuple bond underwent reversible cleavage/formation, corroborated by the characterization of two inverted arene sandwich dichromium complexes (μ-η6:η6-1,3,5-(Me3Si)3C6H3)[Cr{κ2-HC(N-2,6-iPr2C6H3)(N-2,6-R2C6H3)}]2 (R = iPr (5), Me (8)). In the presence of σ donors such as THF and 2,4,6-Me3C6H2CN, the bridging arene 1,3,5-(Me3Si)3C6H3 in 5 and 8 was extruded and 1 and 7 were regenerated. Theoretical calculations were employed to disclose the reaction pathways of these highly regioselective [2+2+2] cylcotrimerization reactions of terminal alkynes.
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High Susceptibility of Histidine to Charge Solvation Revealed by Cold Ion Spectroscopy ()
Histidine remained the last aromatic amino acid for which the intrinsic spectroscopic properties and structures were obscure. We measured the UV and IR spectra of protonated histidine, isolated in the gas phase, using photofragmentation cold ion spectroscopy. Unexpectedly, the UV absorption appears strongly redshifted relative to that of the cation in aqueous solutions. In investigating this phenomenon, we solved the geometries of all abundant conformers using IR conformer-selective spectroscopy and ab initio quantum chemical calculations. In all of the structures, the proton resides on the imidazole ring. The measured UV spectra of protonated methylimidazole, histamine, and histidine, together with calculations of the electronic spectra for the latter, suggest that, in comparison with other aromatic amino acids, such location of proton makes UV absorption of histidine highly sensitive to the local environment of its side chain.
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A pH-Dependent, Mechanically Interlocked Switch: Organometallic [2]Rotaxane vs. Organic [3]Rotaxane ()
We present the first [2]rotaxane featuring an organometallic host. In contrast to the known organic scaffolds, this assembly shows a high post-synthetic modifiability: The reactivity of the Ag8-pillarplex host is fully retained as is exemplified by the first transmetallation in a rotaxane framework to the respective Au8-analogue. Additionally, an acidic transformation to a purely organic [3]rotaxane is demonstrated which is reversible upon addition of an adequate base - rendering the assembly a pH-dependent switch. Hereby, it is shown that the mechanically interlocked nature of the system enhances the kinetic stability of the NHC host complex by a factor of > 1000 which resembles the first observation of a stabilizing "rotaxand-effect".
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Polyproline is a minimal antifreeze protein mimetic and enhances the cryopreservation of cell monolayers ()
Tissue engineering, gene therapy, drug screening and emerging regenerative medicine therapies are fundamentally reliant on high-quality adherent cell culture, but current methods to cryopreserve cells in this format can give low cell yields and requires large volumes of solvent 'antifreezes'. Herein we report polyproline is a minimum (bio)synthetic mimic of antifreeze proteins, which is accessible by solution, solid phase and recombinant methods. We demonstrate that polyproline has ice recrystallization inhibition activity linked to its amphipathic helix and that it enhances the DMSO- cryopreservation of adherent cell lines. Polyproline may be a versatile additive in the emerging field of macromolecular cryoprotectants.
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Oxidation of Organic Molecules with a Redox-Active Guanidine Catalyst ()
Herein we report the first examples for the use of redox-active guanidines as catalysts in the green oxidation of organic molecules with dioxygen. In one half-reaction, the oxidized state of the redox-active guanidine is converted to the reduced, protonated state, thereby enabling dehydrogenative oxidation of the substrate (3,5-ditertbutylcatechol o-benzoquinone, benzoin benzil, and 2,4-ditertbutylphenol biphenol). In the other half-reaction, efficient re-oxidation of the guanidine to the oxidized state is achieved with dioxygen in the presence of a copper catalyst. The results pave the way for a broader use of redox-active guanidines as oxidation catalysts.
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Breaking bonds, Forming Nanographene Diradicals with Pressure ()
New anthanthrone-based polycyclic scaffolds possessing peripheral crowed quinodimethanes have been prepared. While the compounds adopt a closed-shell butterfly shaped structure in the ground state, a curved-to-planar fluxional dynamic inversion is accessible with a low energy barrier through a diradical transition-state. Mainly driven by the release of strain attributed to the steric hindrance at the peri position of the anthanthrone core, a low-lying diradical state is accessible through planarization of the core. The most significant aspect is that planarization is also achieved by application of mild pressure in the solid state, wherein the diradical remains kinetically trapped. Cross-information from quantum chemistry, 1H NMR and Raman spectroscopies together with magnetic experiments allow us to propose the formation of a nanographene-like structure which possesses unpaired electrons radical centers mainly localized at the exo-anthanthrone carbons bearing phenyl substituents.
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C3-Symmetric Tricyclo[2.2.1.02,6]heptane-3,5,7-triol ()
A straightforward access to a hitherto unknown C3-symmetric tricyclic triol both in racemic and enantiopure forms has been elaborated. Treatment of 7-tert-butoxynorbornadiene with peroxycarboxylic acids provided mixtures of C1- and C3-symmetric 3,5,7-triacyloxy-nortricyclenes via transannular π-cyclization and substitution of the tert-butoxy group. Refluxing in formic acid, the C1-symmetric esters were converted to the C3-symmetric formate. Hydrolysis gave diastereoisomeric triols, which were separated by recrystallization. Enantiomer resolution via diastereoisomeric tri(O-methylmandelates) delivered the target triols in gram scale. The pure enantiomers are useful as core units of dopants for liquid crystals.
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Side Group-Mediated Mechanical Conductance Switching in Molecular Junctions ()
A key target in molecular electronics has been molecules having switchable electrical properties. Switching between two electrical states has been demonstrated using such stimuli as light, electrochemical voltage, complexation and mechanical modulation. A classic example of the latter is the switching of 4,4'-bipyridine, leading to conductance modulation of ~1 order of magnitude. Here, we describe the use of side-group chemistry to control the properties of a single-molecule electromechanical switch, which can be cycled between two conductance states by repeated compression and elongation. While bulky alkyl substituents inhibit the switching behaviour, -conjugated side-groups reinstate it. DFT calculations show that weak interactions between aryl moieties and the metallic electrodes are responsible for the observed phenomenon. This represents a significant expansion of the single-molecule electronics "tool-box" for the design of junctions with electromechanical properties.
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Surface-assisted self-assembly strategies leading to supramolecular hydrogels ()
Localized molecular self-assembly processes leading to the growth of nanostructures exclusively from the surface of a material is one of the great challenges in surface chemistry. In the last decade, several works have been reported about the ability of modified or unmodified surfaces to manage the self-assembly of low molecular weight hydrogelators (LMWH) resulting in localized supramolecular hydrogel coatings mainly based on nanofiber architectures. This minireview highlights all strategies that emerged recently to initiate and localize LMWH supramolecular hydrogel formation, their related fundamental issues and applications.
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Aqueous Gold Overgrowth of Silver Nanoparticles: Merging the Plasmonic Properties of Silver with the Functionality of Gold ()
To date, it has not been possible to combine the high optical quality of silver particles with good chemical stability and synthetic convenience in a fully aqueous system, while simultaneously allowing chemical surface functionalization. We present a synthetic pathway for future developments in information, energy and medical technology where strong optical/electronic properties are crucial. Therefore, the advantages inherent to gold are fused with the plasmonic properties of silver in a fully aqueous Au/Ag/Au core-shell-shell system. These nanoparticles inherit low dispersity from their masked gold cores, yet simultaneously exhibit the strong plasmonic properties of silver. Protecting the silver surface with a sub-skin depth gold layer enables oxidant stability and functionality without altering the Ag-controlled optical properties. This combines both worlds - optical quality and chemical stability - and furthermore it is not limited to a specific particle shape.
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Direct Synthesis of Polymer Nanotubes via Aqueous Dispersion Polymerization of Cyclodextrin/Styrene Complex ()
We report a one-step synthesis of nanotubes by RAFT dispersion polymerization of cyclodextrin/styrene (CD/St) complexes directly in water. The resulted amphiphilic PEG-b-PS diblock copolymers self-assemble in situ into nanoparticles with various morphologies. Spheres, worms, lamellae, and nanotubes were controllably obtained. Because of the complexation, the swelling degree of polystyrene (PS) blocks by free St is limited, resulting limited mobility of PS chains. Consequently, kinetically trapped lamellae and nanotubes were obtained instead of spherical vesicles. During the formation of nanotubes, small vesicles firstly formed at the ends of the tape-like lamellae, then grew and fused into nanotubes with limited chain rearrangement. The introduction of host-guest interaction based on CDs enables the aqueous dispersion polymerization of water-immiscible monomers, and produces kinetically trapped nanostructures, which could be a powerful technique for nanomaterials synthesis.
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Supramolecular recognition allows remote, site-selective C-H oxidation of methylenic sites in linear amines ()
Site-selective C-H functionalization of aliphatic alkyl chains stands as a longstanding challenge in oxidation catalysis, given the comparable relative reactivity of the different methylenes. Herein, we describe a supramolecular, bioinspired approach to address this challenge. We decorated a manganese complex, able to catalyze C(sp3)-H hydroxylation with H2O2, with a supramolecular receptor (an 18-benzocrown-6 ether) that binds ammonium substrates via hydrogen bonding. Reversible pre-association of protonated primary aliphatic amines with the crown ether thus selectively exposes only remote positions (C8 and C9) to the oxidizing unit, yielding the site-selective oxidation and overriding the intrinsic reactivity of C-H bonds. Remarkably, the supramolecular control of the selectivity holds true for a whole series of linear amines, no matter the chain length and the presence of more (sterically) activated sites.
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Meso-aryl [20]π Homoporphyrin: The simplest expanded porphyrin with smallest Möbius Topology ()
The unstable conjugated homoporphyrin is successfully stabilized by introducing the meso-aryl substitutents. It was evident from the moderate diatropic ring current in NMR analysis that the newly formed 20π conjugated freebase and its protonated form exhibit the Möbius aromatic character. Further, the complexation of ligand with Rh(I) salt afforded a unique binding mode and retaining Möbius aromaticity. Overall, these are the smallest Möbius aromatic molecules, which are unambiguously confirmed by spectral, crystal analyses and supported by theoretical studies.
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Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular Polymerization ()
We present a multi-stimuli responsive transient supramolecular polymerization of ß-sheet encoded dendritic peptide monomers in water. The glutamic acid and methionine containing amphiphiles undergo a glucose oxidase-catalyzed, glucose-fueled transient hydrogelation in response to an interplay of pH- and oxidation-stimuli, promoted by the production of reactive oxygen species (ROS). By adjusting the enzyme and glucose concentration we tune the assembly and the disassembly rates of the supramolecular polymers, which dictate the stiffness and transient stability of the hydrogels. The incorporation of triethylene glycol chains introduces thermoresponsive properties to the materials. We further show that repair enzymes are able to reverse the oxidative damage in the methionine-based thioether side chains. Since ROS play an important role in signal transduction cascades, our strategy offers great potential for applications of these dynamic biomaterials in redox microenvironments.
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Identification of Ubiquitin Chain Interacting Proteins ()
Ubiquitylation, the modification of proteins by ubiquitin (Ub), is one of the most prevalent and versatile post-translational modifications in eukaryotic cells. As Ub also serves as its own substrate, proteins can be modified by numerous different Ub chains, in which the individual moieties are linked via one or several of the seven lysines of Ub. Homogeneous Ub chains, in which the moieties are sequentially linked via the same residue, have been most extensively studied. Yet, due to their restricted availability, the functions of Ub chains linked via K27, K29 or K33 are poorly understood. We have developed an approach that, for the first time, allows the generation of all seven homogeneous Ub chains in large quantities. We show that the chains enable the identification of Ub chain binding proteins by affinity-based proteomics. The potential of our approach is demonstrated by the identification of previously unknown interaction partners of K27-, K29-, and K33-linked Ub chains.
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Single-Molecule Observation of The Photoregulated Conformational Dynamics of DNA Origami Nanoscissors ()
We demonstrate direct observation of the dynamic opening and closing behavior of photo-controllable DNA origami nanoscissors (NS) using high-speed AFM. First the conformational change between the open and closed state controlled by adjustment of salt concentration could be directly observed during AFM scanning. Then light-responsive moieties were incorporated into the NS to control the structural changes by irradiation. Using photo-switchable DNA strands, we created a photoresponsive NS variant and were able to distinguish between the open and closed conformations after respective irradiation with UV and visible (Vis) light via gel electrophoresis and AFM imaging. Additionally, these reversible changes in shape during photoirradiation were directly visualized using HS-AFM. Moreover, four photo-switchable NS were assembled into a scissor-actuator-like higher-order object whose configuration could be controlled by the open and close switching as induced by UV and Vis light irradiation.
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Asymmetric Squaramide Catalyzed Domino aza-Friedel-Crafts/N,O Acetalization Reactions Between 2-Naphthols and Pyrazolinone Ketimines ()
Pyrazolin-5-one derived N-Boc ketimines have been explored to develop an unprecedented domino aza-Friedel-Crafts/N,O-acetalization reaction with 2-naphthols. The novel protocol requires only a catalyst loading of 0.5 mol% of a bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra-substituted stereogenic centers in excellent yields (95-98%) and stereoselectivities (>99:1 dr and 97-98% ee). A different reactivity was observed in the case of 1-naphthols and other electron-rich phenols, which led to the aza-Friedel-Crafts adducts in 70-98% yield and 47-98% ee.
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Mechanism-based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural, and Kinetic Insight ()
The sirtuin enzymes are important regulatory deacylases in a variety of biochemical contexts and may therefore be potential therapeutic targets through either activation or inhibition by small molecules. Here, we describe the discovery of the most potent inhibitor of sirtuin 5 (SIRT5) reported to date. We provide rationalization of the mode of binding by solving co-crystal structures of selected inhibitors in complex with both human and zebrafish SIRT5, which provide insight for future optimization of inhibitors with more "drug-like" properties. Importantly, enzyme kinetic evaluation revealed a slow, tight-binding mechanism of inhibition, which is unprecedented for sirtuins. This is important information when applying inhibitors to probe mechanisms in biology.
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An easy-to-machine electrochemical flow microreactor: Efficient isoindolinone synthesis and flow functionalization ()
Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to isoindolinones. The combination with inline mass spectrometry facilitates a much easier telescoping of chemical steps in a single flow process.
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Discovery of New Click and Release Reactions by Screening of Mesoionics and Cycloalkynes Combinations ()
We report the discovery of a new bioorthogonal click and release reaction involving imino-sydnones and strained alkynes. This transformation leads to two products resulting from both ligation and fragmentation of imino-sydnones under physiological conditions. Optimized imino-sydnones were successfully used to design innovative cleavable linkers for protein modifications opening new areas in the fields of drug release and target fishing applications. This click and release technology offers for the first time the possibility to exchange tags on proteins with functionalized cyclooctynes under mild and bioorthogonal conditions.
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Oxyfunctionalization of the remote C-H bonds of aliphatic amines via decatungstate photocatalysis ()
Remotely oxygenated aliphatic amines represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported here is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H2O2 or O2 as the terminal oxidant. Using these conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value added ketone products. Lastly, in situ LED-irradiated NMR spectroscopy was utilized to monitor the kinetics of the reaction, enabling direct translation of the reaction in flow.
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Enantioselective Copper-Catalyzed Alkylation of Quinoline N-Oxides with Vinylarenes ()
We report an asymmetric copper-catalyzed alkylation of quinoline N-oxides with chiral Cu-alkyl species generated by migratory insertion of vinylarene into a chiral Cu-H complex. A variety of quinoline N-oxides and vinylarenes underwent this Cu-catalyzed enantioselective alkylation reaction, yielding the corresponding chiral alkylated N-heteroarenes in high isolated yields with high to excellent enantioselectivities. This enantioselective protocol represents the first general and practical approach to access a wide range of chiral alkylated quinolines.
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Experimental proof of the bifunctional mechanism for the hydrogen oxidation in alkaline media ()
Realization of the hydrogen economy relies on effective hydrogen production, storage, and utilization. The slow kinetics of hydrogen evolution and oxidation reaction (HER/HOR) in alkaline media limits many practical applications involving hydrogen generation and utilization, and how to overcome this fundamental limitation remains debatable. Here we present a kinetic study of the HOR on representative catalytic systems in alkaline media. Electrochemical measurements show that the HOR rate of Pt-Ru/C and Ru/C systems is decoupled to their hydrogen binding energy (HBE), challenging the current prevailing HBE mechanism. The alternative bifunctional mechanism is verified by combined electrochemical and in situ spectroscopic data, which provide convincing evidence for the presence of hydroxyl on surface Ru sites in the HOR potential region and its key role in promoting the rate-determining Volmer step. The conclusion presents important references for design and selection of HOR catalysts.
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Living Supramolecular Polymerization of a Perylene Bisimide Dye into Fluorescent J-Aggregates ()
Self-assembly of a new, in bay-position 1,7- dimethoxy-substituted perylene bisimide (PBI) organogelator affords non-fluorescent H-aggregates at fast cooling rates and fluorescent J-aggregates at slow cooling rates. Under properly adjusted conditions the kinetically trapped "off-pathway" H-aggregates transform into the thermodynamically favored J-aggregates, a process that can be accelerated by the addition of J-aggregate seeds. Spectroscopic studies revealed a subtle interplay of pi-pi interactions and intra- and intermolecular hydrogen bonding for monomeric, H- and J-aggregated PBIs. Multiple polymerization cycles initiated from the seed termini demonstrate the living character of this chain-growth supramolecular polymerization process.
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New Insights into the Activation and Deactivation of Au/CeZrO4 in the Low-Temperature Water-Gas Shift Reaction ()
Gold on ceria-zirconia is an active catalyst for the low-temperature water-gas shift reaction (LTS), a key stage of upgrading H2 reformate streams for fuel cells. However, this catalyst rapidly deactivates and the mechanism remains unclear. Using stop-start scanning transmission electron microscopy (STEM) to follow the exact same area of the sample at different stages of the LTS reaction, as well as complementary X-ray photoelectron spectroscopy, we observed the activation and deactivation of the catalyst at various stages. During the heating of the catalyst to reaction temperature, we observed the formation of small Au nanoparticles (1-2 nm) from sub-nm Au species. These nanoparticles then agglomerated further over 48 h on-stream, most rapidly in the first 5 h when the highest rate of deactivation was observed. These findings suggest that the primary deactivation process consists of the loss of active sites through the agglomeration and possible dewetting of Au nanoparticles.
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Silicon Wafers Revealing Facet-Dependent Electrical Conductivity Properties ()
By breaking intrinsic Si (100) and (111) wafers to expose sharp {111} and {112} facets, electrical conductivity measurements on single and different silicon crystal faces have been performed through contacts with two tungsten probes. While Si {100} and {110} faces are barely conductive at low applied voltages as expected, Si {112} surface is highly conductive and Si {111} surface also shows good conductivity. Asymmetrical I-V curves have been recorded for the {111}/{112}, {111}/{110}, and {112}/{110} facet combinations because of different degrees of conduction band bending at these crystal surfaces presenting different barrier heights to current flow. In particular, the {111}/{110}, and {112}/{110} facet combinations give I-V curves resembling those of p-n junctions, suggesting a novel field effect transistor design is possible capitalizing on the pronounced facet-dependent electrical conductivity properties of silicon.
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Near-Infrared-Light-Driven Hydrogen Evolution from Water using a Polypyridyl Triruthenium Photosensitizer ()
In order to realize the artificial photosynthetic devices splitting water to H2 and O2 (2H2O + hν 2H2 + O2), it is desirable to utilize a wider wavelength range of light that extends to a lower energy region of solar spectrum. Here we report a triruthenium photosensitizer [Ru3(dmbpy)6(μ-HAT)]6+ (dmbpy = 4,4'-dimethyl-2,2'-bipyridine, HAT = 1,4,5,8,9,12-hexaazatriphenylene), which absorbs near-infrared light up to 800 nm based on its 1MLCT transition. Importantly, [Ru3(dmbpy)6(μ-HAT)]6+ is found to be the first example of a photosensitizer which can drive H2 evolution under the illumination of near-infrared light above 700 nm. The electrochemical and photochemical studies reveal that the reductive quenching within the ion-pair adducts of [Ru3(dmbpy)6(μ-HAT)]6+ and ascorbate anions affords a singly reduced form of [Ru3(dmbpy)6(μ-HAT)]6+, which is used as a reducing equivalent in the subsequent water reduction process.
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Reduction of a CeIII Siloxide Complex Affords a Tetradecker Arene-bridged CeII Sandwich ()
Organometallic multiple-decker sandwich complexes containing f-elements remain rare in spite of their attractive magnetic and electronic properties. The reduction of the CeIII siloxide complex, [KCeL4] (1; L = OSi(OtBu)3) with excess potassium in a THF/toluene mixture affords a rare tetradecker arene-bridged complex [K(2.2.2-crypt)]2[{(KL3Ce)(µ-η6:η6-C7H8)}2Ce] (3). The structure of 3 features a [Ce(C7H8)2] sandwich capped by [KL3Ce] moieties with a linear arrangement of the Ce ions. Structural parameters, UV-Vis data and DFT studies indicate the presence of CeII ions involved in δ bonding between the Ce cations and toluene dianions. Complex 3 is a rare lanthanide multidecker complex and the first containing non-classical divalent lanthanide ions. Moreover, oxidation of 1 by AgOTf (OTf = O3SCF3) yielded the CeIV complex, [CeL4] (2), showing that siloxide ligands can stabilize Ce in three oxidation states.
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Synthesis of Anisotropic Hydrogels and Their Applications ()
Owing to their water-rich structures similar to biological tissues, hydrogels have long been regarded as promising scaffolds for artificial tissues and organs. However, in terms of structural anisotropy, most synthetic hydrogels are substantially different from biological systems. Synthetic hydrogels are usually composed of randomly oriented three-dimensional polymer networks, whereas biological systems adopt anisotropic structures with hierarchically integrated building units. Such anisotropic structures often play an essential role in biological systems to exhibit their particular functions, as represented by muscular textures comprising unidirectionally oriented actin-myosin units. In this context, anisotropic hydrogels provide an entry point for exploring the biomimetic applications of hydrogels. Reflecting these aspects, an increasing number of studies on anisotropic hydrogels have been reported recently. This Minireview highlights the outline and perspective of these anisotropic hydrogels, particularly focusing on their preparation, structures, and applications.
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Ynamide Preactivation Allows a Regio- and Stereoselective Synthesis of α,β-disubstituted Enamides ()
A novel ynamide preactivation strategy enables the use of otherwise incompatible reagents and allows preparation of α,β-disubstituted enamides with high regio- and stereoselectivity. Mechanistic analysis reveals the intermediacy of a triflate-bound intermediate as a solution-stable, effective keteniminium reservoir, whilst still allowing subsequent addition of organometallic reagents.
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Decatwistacene with a 170 Torsion ()
Two different lengths of twistacenes, namely hexatwistacene and decatwistacene induced by the steric-hindrance effect between imide groups and neighbouring annulated benzene rings, were synthesized via bottom-up synthesis of palladium-catalyzed Suzuki cross-coupling and C-H activation reaction. Single-crystal X-ray analyses revealed that decatwistacene, which is the longest twistacene reported until now, exhibits an astonishing overall end-to-end torsion angle of about 170, the largest torsion angle reported so far. Both twistacenes have an enhanced solubility and stability with respect to light and oxygen due to their large twisting deformations together with much lower LUMO levels caused by the introduction of imide groups, opening a window to the narrowest chiral graphene nanoribbons with good stability and processability.
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A Strategy for Specific Fluorescence Imaging of Monoamine Oxidase A in Living Cells ()
Monoamine oxidase (MAO) has two isoforms, MAO-A and MAO-B, which show different functions and thus selective fluorescence imaging of which is important for biological studies. Currently, however, specific detection of MAO-A remains a great challenge. Herein, we report a new strategy for specific imaging of MAO-A via designing fluorescent probes by combining the characteristic structure of the enzymatic inhibitor with propylamine as a recognition moiety. The high specificity of our representative probe is demonstrated by imaging MAO-A in different live cells such as SH-SY5Y (high level of MAO-A) and HepG2 (high level of MAO-B), as further validated by both control probe and western blot analyses. The superior specificity of the probe may benefit the accurate detection of MAO-A in complex biosystems. Importantly, in this work the use of the characteristic structure of an inhibitor may serve as a general strategy to design a specific recognition moiety of fluorescent probes for an enzyme.
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Feedback kinetics in mechanochemistry; the importance of cohesive states ()
Abstract: Although mechanochemical synthesis is becoming more widely applied and even commercialised, greater basic understanding is needed if the field is to progress on less of a trial-and-error basis. We report that a mechanochemical reaction in a ball mill exhibits unusual sigmoidal feedback kinetics that differ dramatically from the simple first-order kinetics for the same reaction in solution. An induction period followed by a rapid increase in reaction rate before the rate decreases again as the reaction goes to completion. The origin of these unusual kinetics is found to be a feedback cycle involving both chemical and mechanical factors. During the reaction the physical form of the reaction mixture changes from a powder to a cohesive rubber-like state, and this results in the observed reaction rate increase. The study reveals that non-obvious and dynamic rheological changes in the reaction mixture must be appreciated to understand how mechanochemical reactions progress.
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Diastereoselective C-H bond amination for disubstituted pyrrolidines ()
We report herein on the improved diastereoselective synthesis of 2,5-disubstituted pyrrolidines from aliphatic azides. Experimental and theoretical studies of the C-H amination reaction mediated by the iron dipyrrinato complex (AdL)FeCl(OEt2) provided a model for diastereoinduction and allowed for systematic variation of the catalyst to enhance selectivity. Among the iron alkoxide and aryloxide catalysts evaluated, the iron-phenoxide complex exhibited superior performance towards the generation of syn 2,5-disubstituted pyrrolidines with high diastereoselectivity.
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Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines ()
Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and w-transaminase (w-TA) biocatalysts to establish the key stereocentres of these molecules. Several enantiocomplementary IREDs were identified for the synthesis of (R)- and (S)-5-methyl-6,7-dihydro-5H-dibenz[c,e]azepine with excellent enantioselectivity by reduction of the parent imines. Crystallographic evidence suggests that IREDs may be able to bind one conformer of the imine substrate such that, upon reduction, the major product conformer is generated directly. ω-TA biocatalysts were also successfully employed for the production of enantiopure 1-(2-bromophenyl)ethan-1-amine enabling an orthogonal route for the installation of chirality into dibenz[c,e]azepine frameworks.
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C-H Functionalization for Hydrogen Isotope Exchange ()
The varied applications of hydrogen isotopes (deuterium, D, and tritium, T) in the physical and life sciences demands a range of methods for their installation in an array of molecular architectures. In this review, we describe recent advances in synthetic C-H functionalization for hydrogen isotope exchange.
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Visible light-driven and Iron-promoted Thiocarboxylation of Styrenes and Acrylates with CO2 ()
The first thiocarboxylation of styrenes and acrylates with CO2 is realized by using visible light as a driving force and catalytic iron salts as promoters. A variety of important β-thioacids are obtained in high yields. This multicomponent reaction proceeds in an atom- and redox-economical way with broad substrate scope under mild reaction conditions. Notably, high regio-, chemo- and diastero-selectivity are observed. Mechanistic studies indicate that a radical pathway can account for the unusual regioselectivity.
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Ligand and Solvent Controlled Regio- and Chemo-divergent Carbonylative Reactions ()
The development of high selective procedures is one of the core goals in organic chemistry, and the target which generations of chemists are pursuing. Among the known organic transformations, carbonylation reactions present an ideal choice for carbonyl-containing compounds preparation. In this review, the recent achievements on selectivity controlled carbonylation reactions have been summarized. The effects of ligands, solvents and bases on the selectivity have been discussed.
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Unprecedented Sensitivity in a Probe for Detection and Imaging of Cathepsin B: Chemiluminescence Microscopy Cell Images of Natively-Expressed Enzyme ()
Until recently, chemiluminescence cell images could be obtained only using luciferase-activated probes. Moreover, chemiluminescence microscopy cell-imaging was never demonstrated for natively expressed enzymes like cathepsin B. Here we describe the design synthesis and evaluation of the first chemiluminescence probe for detection and imaging of cathepsin B. The probe activation mechanism relies on the release of a dioxetane intermediate, which undergoes chemiexcitation to emit green light with high efficiency under physiological conditions. Using the probe, we obtained clear images of cancerous leukemia and colon cells. This is the first demonstration of chemiluminescence cell images obtained by a probe for a natively-expressed endogenous enzyme. We anticipate that the concept presented in this study will be broadly used to develop analogous probes for other important proteases relevant to biomolecular processes.
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Lanthanide-based T2ex and CEST complexes provide new insights into the design of pH sensitive MRI agents ()
A series of Eu3+ and Dy3+ DOTA-tetraamide complexes with four appended primary amine groups were prepared and their CEST and T1/T2 relaxation properties measured as a function of pH. The CEST signals in the Eu3+ complexes show a surprisingly strong CEST signal after the pH was reduced from 8 to 5. The opposite trend was observed for the Dy3+ complexes where the r2ex of bulk water protons increased dramatically from ~1.5 mM-1s-1 to ~13 mM-1s-1, while r1 remained unchanged. A fit of the CEST data (Eu3+ complexes) to Bloch theory and the T2 data (Dy3+ complexes) to Swift-Connick theory provided the proton exchange rates as a function of pH. These data showed that the four amine groups contribute significantly to proton catalyzed exchange of the Ln3+-bound water protons even though their pka's are much higher than the observed CEST or T2ex effects. This demonstrated the utility of using appended acidic/basic groups to catalyze prototropic exchange for imaging tissue pH by MRI.
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Sequence Mandated, Distinct Assembly of Giant Molecules ()
Although controlling primary structures is by itself an enormous challenge for synthetic polymers, the potential of sequence control for tailoring hierarchical structures remains to be exploited, especially in the creation of new and unconventional phases. Herein, we design a series of model amphiphilic chain-like giant molecules by connecting both hydrophobic and hydrophilic molecular nanoparticles in precisely defined sequence and composition to investigate their intriguing sequence-dependent phase structures. Not only has composition changed the self-assembled phases, but also specific sequences are found to induce unconventional phase formation, including Frank-Kasper phases. The formation mechanism has been attributed to the conformational change driven by the collective hydrogen bonding and the sequence-mandated topology of the molecules. These results support that sequence-control in synthetic polymers can have dramatic impacts on the polymer properties and self-assembly.
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Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols using Additive Horeau Amplification ()
The concept of synergistic double catalytic kinetic resolution (DoCKR) described in this article, was successfully applied to racemic acyclic anti-1,3-diols, a common motif in natural products. This process takes advantage of an additive Horeau amplification involving two successive enantioselective organocatalytic acylations reactions, and leading to diesters and recovered diols with high enantiopurities. It was first developed with C2-symmetrical diols and then further extended to non-C2-symmetrical anti diols to prepare useful chiral building blocks. The protocol is highly practical as it only requires 1 mol% of a commercially available organocatalyst and leads to easily separable products. This procedure was applied to the shortest reported total synthesis of (+)-cryptocaryalactone, a natural product with anti-germinative activity.
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Detailed Evidence for an Unparalleled Interaction Mode between Calmodulin and Orai Proteins ()
Calmodulin (CaM) binds most of its targets by wrapping around an amphipathic α-helix. The N-terminus of Orai proteins contains a conserved CaM-binding segment but the binding mechanism is only partially characterized. Here, microscale thermophoresis (MST), surface plasmon resonance (SPR), and atomic force microscopy (AFM) were employed to study the binding equilibria, the kinetics, and the single-molecular interaction forces involved in the binding of CaM to the conserved helical segments of Orai1 and Orai3. The results consistently indicated step-wise binding of two separate target peptides to the two lobes of CaM. An unparalleled high affinity was found when two Orai peptides were dimerized or immobilized at high lateral density, thereby mimicking the close proximity of the N-termini in native Orai oligomers. The analogous experiments with smooth muscle myosin light chain kinase (smMLCK) showed only the expected 1:1 binding, confirming the validity of our methods.
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Reducing the Charge Carrier Transport Barrier in Functionally Layer-Graded Electrodes ()
Lithium-ion batteries (LIBs) are primary energy storage devices to power consumer electronics and electric vehicles, but their capacity is dramatically decreased at ultrahigh charging/discharging rates. This mainly originates from a high Li-ion/electron transport barrier within a traditional electrode, resulting in reaction polarization issues. To address this limitation, a functionally layer-graded electrode was designed and fabricated to decrease the charge carrier transport barrier within the electrode. As a proof-of-concept, functionally layer-graded electrodes composing of TiO2(B) and reduced graphene oxide (RGO) exhibit a remarkable capacity of 128 mAh g−1 at a high charging/discharging rate of 20 C (6.7 A g−1), which is much higher than that of a traditionally homogeneous electrode (74 mAh g−1) with the same composition. This is evidenced by the improvement of effective Li ion diffusivity as well as electronic conductivity in the functionally layer-graded electrodes. A functionally graded electrode was developed to address reaction polarization issue in lithium-ion batteries by increasing effective Li ion diffusivity as well as electronic conductivity. As evidence, a layer-graded electrode composed of TiO2(B) and reduced graphene oxide exhibits much higher capacity (128 mAh g−1) than that of traditional homogeneous electrode (74 mAh g−1) at a high charging current density of 6.7 A g−1.
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A Peroxisome-Inspired Chemiluminescent Silica Nanodevice for the Intracellular Detection of Biomarkers and Its Application to Insulin-Sensitizer Screening ()
The profiling of oxidase-catalyzed biomarkers is an essential procedure for the diagnosis and precise treatment of metabolic diseases. Inspired by the metabolism of H2O2 in peroxisomes, a novel chemiluminescent silica nanodevice (CSN) was designed for the sensitive and selective sensing of intracellular oxidase-catalyzed biomarkers. Oxidases catalyzed the oxidation of biomarkers followed by the production of H2O2, and then the generated H2O2 was employed to trigger chemiluminescence of the CSN. Utilizing this nanodevice, we not only accurately quantified intracellular glucose but also developed its further application for facile insulin sensitizer screening. Furthermore, sensitive and multiparametric analysis of oxidase-catalyzed biomarkers like lactic acid, uric acid, and ethanol was demonstrated. Thus, this peroxisome-inspired CSN holds great promise for the general diagnosis of metabolic diseases and in drug discovery. Luminescent peroxisomes: A peroxisome-inspired chemiluminescent silica nanodevice (see figure; grey sphere) was designed for the sensitive and selective intracellular profiling of biomarkers by using the oxidase-catalyzed generation of H2O2. This nanodevice was used to accurately quantify intracellular glucose. Furthermore, its applications to insulin-sensitizer screening and multiparametric biomarker analysis were demonstrated.
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Rapid Guest Exchange and Ultra-Low Surface Tension Solvents Optimize Metal–Organic Framework Activation ()
Exploratory research into the critical steps in metal–organic framework (MOF) activation involving solvent exchange and solvent evacuation are reported. It is discovered that solvent exchange kinetics are extremely fast, and minutes rather days are appropriate for solvent exchange in many MOFs. It is also demonstrated that choice of a very low surface tension solvent is critical in successfully activating challenging MOFs. MOFs that have failed to be activated previously can achieve predicted surface areas provided that lower surface tension solvents, such as n-hexane and perfluoropentane, are applied. The insights herein aid in the efficient activation of MOFs in both laboratory and industrial settings and provide best practices for avoiding structural collapse. An exchange for the better: Activation involving solvent exchange and evacuation is crucial to achieve maximum surface area and gas-storage properties in metal–organic frameworks (MOFs). Porosity is preserved when fast solvent exchange kinetics and ultra-low surface tension solvents are exploited yielding MOFs without structural collapse.
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Structural Snapshots of α-1,3-Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases ()
Glycosyltransferases (GTs) are a key family of enzymes that catalyze the synthesis of glycosidic bonds in all living organisms. The reaction involves the transfer of a glycosyl moiety and can proceed with retention or inversion of the anomeric configuration. To date, the catalytic mechanism of retaining GTs is a topic of great controversy, particularly for those enzymes containing a putative nucleophilic residue in the active site, for which the occurrence of a double-displacement mechanism has been suggested. We report native ternary complexes of the retaining glycosyltransferase α-1,3-galactosyltransferase (α3GalT) from Bos taurus, which contains such a nucleophile in the active site, in a productive mode for catalysis in the presence of its sugar donor UDP-Gal, the acceptor substrate lactose, and the divalent cation cofactor. This new experimental evidence supports the occurrence of a front-side substrate-assisted SNi-type reaction for α3GalT, and suggests a conserved common catalytic mechanism among retaining GTs. Crystal clear: A crystal structure was obtained for a native ternary complex of the GT6 family glycosyltransferase α-1,3-galactosyltransferase (α3GalT), which contains a putative nucleophile in the active site, in a productive mode for catalysis. The configuration of the active center supports the occurrence of a front-side substrate-assisted SNi-type reaction, and suggests a conserved common catalytic mechanism among retaining glycosyltransferases.
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Direct Synthesis of Amides by Dehydrogenative Coupling of Amines with either Alcohols or Esters: Manganese Pincer Complex as Catalyst ()
The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable. Just a pinc(h): The first example of base-metal-catalysed synthesis of amides from the coupling of primary amines with either alcohols or esters is reported. The reactions are catalysed by a new manganese pincer complex and generate hydrogen gas as the sole byproduct, thus making the overall process atom-economical and sustainable.
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Generalized Self-Doping Engineering towards Ultrathin and Large-Sized Two-Dimensional Homologous Perovskites ()
Two-dimensional (2D) homologous perovskites are arousing intense interest in photovoltaics and light-emitting fields, attributing to significantly improved stability and increasing optoelectronic performance. However, investigations on 2D homologous perovskites with ultrathin thickness and large lateral dimension have been seldom reported, being mainly hindered by challenges in synthesis. A generalized self-doping directed synthesis of ultrathin 2D homologous (BA)2(MA)n−1PbnBr3n+1 (1
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Oxetane Grafts Installed Site-Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo ()
A four-membered oxygen ring (oxetane) can be readily grafted into native peptides and proteins through site-selective bis-alkylation of cysteine residues present as disulfides under mild and biocompatible conditions. The selective installation of the oxetane graft enhances stability and activity, as demonstrated for a range of biologically relevant cyclic peptides, including somatostatin, proteins, and antibodies, such as a Fab arm of the antibody Herceptin and a designed antibody DesAb-Aβ against the human Amyloid-β peptide. Oxetane grafting of the genetically detoxified diphtheria toxin CRM197 improves significantly the immunogenicity of this protein in mice, which illustrates the general utility of this strategy to modulate the stability and biological activity of therapeutic proteins containing disulfides in their structures. Graft to stabilize: An efficient one-pot method introduces oxetane grafts on native disulfides of peptides and proteins under biocompatible aqueous conditions. This method allows stabilization of folded structures (four examples shown) and enhancement of their biological activity in vitro and in vivo.
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Total Synthesis of (−)-Spiroleucettadine ()
One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans-fused 5,5-bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (−)-spiroleucettadine by a highly efficient biomimetic approach starting from l-tyrosine. One of two key hypervalent-iodine-mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure–biological-activity relationships of these antibacterial compounds. Short and to the point: A highly efficient biomimetic approach enabled the total synthesis of (−)-spiroleucettadine (1), an antibacterial marine natural product densely packed with heteroatoms. One of two key oxidation reactions mediated by hypervalent iodine reagents was used to construct the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step.
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Single and Twofold Metal- and Reagent-Free Anodic C−C Cross-Coupling of Phenols with Thiophenes ()
The first electrochemical dehydrogenative C−C cross-coupling of thiophenes with phenols has been realized. This sustainable and very simple to perform anodic coupling reaction enables access to two classes of compounds of significant interest. The scope for electrochemical C−H-activating cross-coupling reactions was expanded to sulfur heterocycles. Previously, only various benzoid aromatic systems could be converted, while the application of heterocycles was not successful in the electrochemical C−H-activating cross-coupling reaction. Here, reagent- and metal-free reaction conditions offer a sustainable electrochemical pathway that provides an attractive synthetic method to a broad variety of bi- and terarylic products based on thiophenes and phenols. This method is easy to conduct in an undivided cell, is scalable, and is inherently safe. The resulting products offer applications in electronic materials or as [OSO]2− pincer-type ligands. First into the congested vicinity of sulfur and then to the other side—these are the positions wherein the dehydrogenative arylation reaction occurs. This allows thiophenes to be easily equipped with hydroxyphenyl moieties in a very simple to perform and scalable procedure from common precursors.
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A Low-Cost Neutral Zinc–Iron Flow Battery with High Energy Density for Stationary Energy Storage ()
Flow batteries (FBs) are one of the most promising stationary energy-storage devices for storing renewable energy. However, commercial progress of FBs is limited by their high cost and low energy density. A neutral zinc–iron FB with very low cost and high energy density is presented. By using highly soluble FeCl2/ZnBr2 species, a charge energy density of 56.30 Wh L−1 can be achieved. DFT calculations demonstrated that glycine can combine with iron to suppress hydrolysis and crossover of Fe3+/Fe2+. The results indicated that an energy efficiency of 86.66 % can be obtained at 40 mA cm−2 and the battery can run stably for more than 100 cycles. Furthermore, a low-cost porous membrane was employed to lower the capital cost to less than $ 50 per kWh, which was the lowest value that has ever been reported. Combining the features of low cost, high energy density and high energy efficiency, the neutral zinc–iron FB is a promising candidate for stationary energy-storage applications. Even flow: A neutral zinc–iron flow battery with very low cost and high energy density is presented. By using highly soluble FeCl2/ZnBr2 species, a charge energy density of 56.30 Wh L−1 can be achieved. DFT calculations demonstrated that glycine can combine with iron to suppress hydrolysis and crossover of Fe3+/Fe2+. An energy efficiency of 86.66 % can be obtained at 40 mA cm−2 and the battery can run stably for more than 100 cycles.
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Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane-Spanning Protein ()
Mapping the interaction sites between membrane-spanning proteins is a key challenge in structural biology. In this study a carbene-footprinting approach was developed and applied to identify the interfacial sites of a trimeric, integral membrane protein, OmpF, solubilised in micelles. The diazirine-based footprinting probe is effectively sequestered by, and incorporated into, the micelles, thus leading to efficient labelling of the membrane-spanning regions of the protein upon irradiation at 349 nm. Areas associated with protein–protein interactions between the trimer subunits remained unlabelled, thus revealing their location. A distinctive footprint: A carbene-footprinting approach was used to identify the interfacial sites of a trimeric integral membrane protein solubilised in micelles. The diazirine probe was incorporated into the micelles and labelled the membrane-spanning regions of the protein upon irradiation at 349 nm (see picture). Areas associated with protein–protein interactions between the trimer subunits remained unlabelled, thus revealing their location.
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Quantifying Guest Exchange in Supramolecular Systems ()
The ability to accurately determine and quantitatively evaluate kinetic phenomena associated with supramolecular assemblies, in real time, is key to a better understanding of their defined architectures and diverse functionalities. Therefore, analytical tools that can precisely assess a wide range of exchange rates within such systems are of considerable importance. This study demonstrates the ability to use an NMR approach based on saturation transfer for the determination of rates of guest exchange from molecular capsules. By using cavitands that assemble into distinct dimeric assemblies, we show that this approach, which we term guest exchange saturation transfer (GEST), allows the use of a conventional NMR setup to study and quantitatively assess a wide range of exchange rates, from 35 to more than 5000 s−1. Don't put up with sneaky guests: Guest exchange saturation transfer (GEST), an NMR-based approach for studying dynamic supramolecular assemblies, enabled the quantitative determination of exchange processes in cavitand dimeric capsules (see picture), even when there was no indication of complex formation by 1H or 19F NMR spectroscopy. By using various guests, a wide range of exchange rates were extracted, from 35 to more than 5000 s−1.
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Three-Dimensional Printing with Biomass-Derived PEF for Carbon-Neutral Manufacturing ()
Biomass-derived poly(ethylene-2,5-furandicarboxylate) (PEF) has been used for fused deposition modeling (FDM) 3D printing. A complete cycle from cellulose to the printed object has been performed. The printed PEF objects created in the present study show higher chemical resistance than objects printed with commonly available materials (acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), glycol-modified poly(ethylene terephthalate) (PETG)). The studied PEF polymer has shown key advantages for 3D printing: optimal adhesion, thermoplasticity, lack of delamination and low heat shrinkage. The high thermal stability of PEF and relatively low temperature that is necessary for extrusion are optimal for recycling printed objects and minimizing waste. Several successive cycles of 3D printing and recycling were successfully shown. The suggested approach for extending additive manufacturing to carbon-neutral materials opens a new direction in the field of sustainable development. From cellulose to the printed object: Biomass-derived poly(ethylene-2,5-furandicarboxylate) (PEF) was used as an efficient material for fused deposition modeling 3D printing. A complete cycle from cellulose to the printed object has been performed. The printed PEF objects reported in the present study show higher chemical resistance than objects printed with commonly available materials.
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Transient Behavior of the Metal Interface in Lithium Metal–Garnet Batteries ()
The interface between solid electrolytes and Li metal is a primary issue for solid-state batteries. Introducing a metal interlayer to conformally coat solid electrolytes can improve the interface wettability of Li metal and reduce the interfacial resistance, but the mechanism of the metal interlayer is unknown. In this work, we used magnesium (Mg) as a model to investigate the effect of a metal coating on the interfacial resistance of a solid electrolyte and Li metal anode. The Li–Mg alloy has low overpotential, leading to a lower interfacial resistance. Our motivation is to understand how the metal interlayer behaves at the interface to promote increased Li-metal wettability of the solid electrolyte surface and reduce interfacial resistance. Surprisingly, we found that the metal coating dissolved in the molten piece of Li and diffused into the bulk Li metal, leading to a small and stable interfacial resistance between the garnet solid electrolyte and the Li metal. We also found that the interfacial resistance did not change with increase in the thickness of the metal coating (5, 10, and 100 nm), due to the transient behavior of the metal interface layer. Resistance is futile: Magnesium was used as a model material to investigate the effect of a metal coating on the interfacial resistance between the garnet (Li7La3Zr2O12) solid electrolyte and the Li metal anode in a Li–garnet solid-state battery. Surprisingly, the metal coating dissolves and diffuses into the bulk Li metal, leading to a small and stable interfacial resistance.
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A Radiolabeling-Free, qPCR-Based Method for Locus-Specific Pseudouridine Detection ()
Pseudouridine (Ψ) is the most abundant post-transcriptional RNA modification. Methods have been developed for locus-specific Ψ detection; however, they often involve radiolabeling of RNA, require advanced experimental skills, and can be time-consuming. Herein we report a radiolabeling-free, qPCR-based method to rapidly detect locus-specific Ψ. Pseudouridine residues were labeled chemically, and the resulting adducts induced mutation/deletion during reverse transcription (RT) to generate qPCR products with different melting temperatures and hence altered melting curves. We validated our method on known Ψ sites in rRNA and then used it to sensitively detect Ψ residues in lncRNA and mRNA of low abundance. Finally, we applied our method to pseudouridine synthase identification and showed that Ψ616 in PSME2 mRNA is dependent on PUS7. Our facile and cost-effective method takes only 1.5 days to complete, and with slight adjustment it can be applied to the detection of other epitranscriptomic marks. A day and a half to complete the hunt: A rapid and cost-effective method has been developed to detect pseudouridine, a prevalent post-transcriptional RNA modification, in the human transcriptome. Pseudouridine was labeled chemically, and the resulting adducts induced mutation/deletion during reverse transcription (RT) to generate qPCR products with different melting temperatures and hence altered melting curves (see picture).
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Ethers on Si(001): A Prime Example for the Common Ground between Surface Science and Molecular Organic Chemistry ()
By using computational chemistry it has been shown that the adsorption of ether molecules on Si(001) under ultrahigh vacuum conditions can be understood with classical concepts of organic chemistry. Detailed analysis of the two-step reaction mechanism—1) formation of a dative bond between the ether oxygen atom and a Lewis acidic surface atom and 2) nucleophilic attack of a nearby Lewis basic surface atom—shows that it mirrors acid-catalyzed ether cleavage in solution. The O−Si dative bond is the strongest of its kind, and the reactivity in step 2 defies the Bell–Evans–Polanyi principle. Electron rearrangement during C−O bond cleavage has been visualized with a newly developed method for analyzing bonding, which shows that the mechanism of nucleophilic substitutions on semiconductor surfaces is identical to molecular SN2 reactions. Our findings illustrate how surface science and molecular chemistry can mutually benefit from each other and unexpected insight can be gained. The not-so-odd couple: A computational study of ethers on Si(001) has shown the commonalities of surface science and molecular chemistry. Quantitative insight into the bonding situation and reactivity demonstrates that these systems can be understood with classical reaction concepts of organic chemistry.
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Cobalt versus Osmium: Control of Both trans and cis Selectivity in Construction of the EFG Rings of Pectenotoxin 4 ()
Catalytic oxidative cyclisation reactions have been employed for the synthesis of the E and F rings of the complex natural product target pectenotoxin 4. The choice of metal catalyst (cobalt- or osmium-based) allowed for the formation of THF rings with either trans or cis stereoselectivity. Fragment union using a modified Julia reaction then enabled the synthesis of an advanced synthetic intermediate containing the EF and G rings of the target. Two types of oxidative cyclisation reaction, utilising either osmium or cobalt catalysis, provide complete control of the relative stereochemistry of THF rings embedded in the complex pectenotoxin-4 ring system. In this manner, rapid access to either trans (Co) or cis (Os) 2,5-disubstituted THF rings of the natural product molecule was facilitated.
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Hydrogen Peroxide Insular Dodecameric and Pentameric Clusters in Peroxosolvate Structures ()
Peroxosolvates of 2-aminonicotinic acid (I) and lidocaine N-oxide (II) including the largest insular hydrogen peroxide clusters were isolated and their crystal structures were determined by single-crystal X-ray diffraction. An unprecedented dodecameric hydrogen peroxide insular cluster was found in I. An unusual cross-like pentameric cluster was observed in the structure of II. The topology of the (H2O2)12 assembly was never observed for small-molecule clusters. In I and II new double and triple cross-orientational disorders of H2O2 were found. Cluster II is the first example of a peroxosolvate crystal structure containing H2O2 molecules with a homoleptic hydrogen peroxide environment. In II, a hydrogen bond between an H2O2 molecule and a peptide group -CONH⋅⋅⋅O2H2 was observed for the first time. Peroxide bond: Peroxosolvates of 2-aminonicotinic acid (I) and lidocaine N-oxide (II) including unprecedented dodecameric and pentameric discrete hydrogen peroxide clusters were isolated and their structures were determined by single-crystal X-ray diffraction. In I and II new double and triple cross-orientational disorders of H2O2 were found. In II, a hydrogen bond between an H2O2 molecule and a peptide group was observed for the first time.
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Gérard Férey (1941–2017) ()
Gérard Férey, a leader in the field of solid-state chemistry and a pioneer of metal–organic frameworks (MOFs), passed away on August 19, 2017 in Paris. Férey developed both open-framework templated metal fluorophosphates (the ULM-n series) and a series of topical porous MOFs (the MIL-n series). He also created the automated assembly of secondary building units methodology to predict the structure of new porous solids.
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Synthesis of Octaaryl Naphthalenes and Anthracenes with Different Substituents ()
A synthesis of multiply arylated naphthalenes and anthracenes with eight different substituents has been accomplished. The key intermediates are tetraarylthiophene S-oxides, which are synthesized through a method involving sequential C−H arylation and cross-coupling from 3-methoxythiophene, followed by oxidation of the sulfur atom. The resulting tetraarylthiophene S-oxides can be converted into a tetraaryl benzynes or naphthalynes and then merged through [4+2] cycloaddition reaction with another tetraarylthiophene S-oxide, thereby resulting in the programmed synthesis of octaarylnaphthalenes and octaarylanthracenes. Straight to eight: A novel method is presented that enables the synthesis of octaarylnaphthalenes (OANs) and octaarylanthracenes (OAAs) with eight different aryl substituents through [4+2] cycloaddition of tetraarylthiophene S-oxides with multiply arylated arynes.
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Characterization of the Conjugation Pattern in Large Polysaccharide–Protein Conjugates by NMR Spectroscopy ()
Carbohydrate-based vaccines are among the safest and most effective vaccines and represent potent tools for prevention of life-threatening bacterial infectious diseases, like meningitis and pneumonia. The chemical conjugation of a weak antigen to protein as a source of T-cell epitopes generates a glycoconjugate vaccine that results more immunogenic. Several methods have been used so far to characterize the resulting polysaccharide–protein conjugates. However, a reduced number of methodologies has been proposed for measuring the degree of saccharide conjugation at the possible protein sites. Here we show that detailed information on large proteins conjugated with large polysaccharides can be achieved by a combination of solution and solid-state NMR spectroscopy. As a test case, a large protein assembly, l-asparaginase II, has been conjugated with Neisseria meningitidis serogroup C capsular polysaccharide and the pattern and degree of conjugation were determined. Solid-state NMR spectra of highly glycosylated proteins (E. coli l-Asparaginase-II) have been obtained showing a remarkable quality. Based on this observation, a protocol that combines solution and solid-state NMR methods was developed to obtain a semi-quantitative evaluation of the conjugation degree and pattern in glycoconjugate vaccines.
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Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells ()
Strongly luminescent iridium(III) complexes, [Ir(C,N)2(S,S)]+ (1) and [Ir(C,N)2(O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X-ray crystallography and DFT calculations. Their long phosphorescence lifetimes in living cancer cells give rise to high quantum yields for the generation of 1O2, with large 2-photon absorption cross-sections. 2 is nontoxic to cells, but potently cytotoxic to cancer cells upon brief irradiation with low doses of visible light, and potent at sub-micromolar doses towards 3D multicellular tumor spheroids with 2-photon red light. Photoactivation causes oxidative damage to specific histidine residues in the key proteins in aldose reductase and heat-shock protein-70 within living cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of enzymes involved in the glycolytic pathway. In for a shock: A highly luminescent organoiridium complex generates 1O2 efficiently and oxidizes specific residues of heat-shock protein-70 and aldose reductase within cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of the enzymes involved in the glycolytic pathway.
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Selective Reduction of CO2 to a Formate Equivalent with Heterobimetallic Gold- - -Copper Hydride Complexes ()
A series of heterobimetallic complexes containing three-center, two-electron Au−H−Cu bonds have been prepared from addition of a parent gold hydride to a bent d10 copper(I) fragment. These highly unusual heterobimetallic complexes represent a missing link in the widely investigated series of neutral and cationic coinage metal hydride complexes containing Cu−H−Cu and M−H−M+ moieties (M=Cu, Ag). The well-defined heterobimetallic hydride complexes act as precatalysts for the conversion of CO2 into HCO2Bpin with HBpin as the reductant. The selectivity of the heterobimetallic complexes for the catalytic production of a formate equivalent surpasses that of the parent monomeric Group 11 complexes. The golden touch: A series of heterobimetallic complexes containing three-center, two-electron Au−H−Cu bonds have been prepared. These unusual molecules represent a missing link in the widely investigated series of neutral and cationic coinage metal hydride complexes containing Cu−H−Cu and M−H−M+ moieties (M=Cu, Ag), and act as precatalysts for the selective reduction of CO2 to HCO2Bpin.
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Palladium-Catalyzed Cross-Coupling of Nitroarenes ()
Pd at the crossroads: The palladium-catalyzed cross-coupling of nitroarenes has eluded chemists for decades. Recently, the first palladium-catalyzed Suzuki–Miyaura and Buchwald–Hartwig cross-couplings of nitroarenes were reported. Mechanistically, this process involves the challenging oxidative addition of LPd0 into the Ar−NO2 bond. This process features a broad substrate scope with respect to both the nitroarene and the nucleophilic coupling partners.
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Oxidative Rearrangement Coupling Reaction for the Functionalization of Tetrahydro-β-carbolines with Aromatic Amines ()
The observation of an unexpected oxidative rearrangement coupling reaction led to the development of a novel method for the efficient functionalization of tetrahydro-β-carbolines (THβCs). The treatment of THβCs with photogenerated singlet oxygen (1O2) afforded unstable dioxetanes, which underwent further transformation to form new bonds in the presence of trifluoroacetic acid. This operationally simple protocol exhibits broad functional-group tolerance and is suitable for the late-stage functionalization of complex druglike molecules. All rearrange please: The treatment of tetrahydro-β-carbolines with photogenerated singlet oxygen led to unstable dioxetanes, which underwent ring opening to give synthetic intermediates with a nine-membered ring. These products reacted with amines in the presence of an acid to form a variety of amino-substituted dihydropyrroloquinolines (see scheme). This simple method is suitable for the late-stage functionalization of complex druglike molecules.
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High Sulfur Content Material with Stable Cycling in Lithium-Sulfur Batteries ()
We demonstrate a novel crosslinked disulfide system as a cathode material for Li-S cells that is designed with the two criteria of having only a single point of S−S scission and maximizing the ratio of S−S to the electrochemically inactive framework. The material therefore maximizes theoretical capacity while inhibiting the formation of polysulfide intermediates that lead to parasitic shuttle. The material we report contains a 1:1 ratio of S:C with a theoretical capacity of 609 mAh g−1. The cell gains capacity through 100 cycles and has 98 % capacity retention thereafter through 200 cycles, demonstrating stable, long-term cycling. Raman spectroscopy confirms the proposed mechanism of disulfide bonds breaking to form a S−Li thiolate species upon discharge and reforming upon charge. Coulombic efficiencies near 100 % for every cycle, suggesting the suppression of polysulfide shuttle through the molecular design. Put a ring on it: A crosslinked disulfide material with high sulfur content displays stable cycling in a lithium-sulfur battery with no evidence of the detrimental polysulfide shuttle.
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Toward Cost-Effective Manufacturing of Silicon Solar Cells: Electrodeposition of High-Quality Si Films in a CaCl2-based Molten Salt ()
Electrodeposition of Si films from a Si-containing electrolyte is a cost-effective approach for the manufacturing of solar cells. Proposals relying on fluoride-based molten salts have suffered from low product quality due to difficulties in impurity control. Here we demonstrate the successful electrodeposition of high-quality Si films from a CaCl2-based molten salt. Soluble SiIV−O anions generated from solid SiO2 are electrodeposited onto a graphite substrate to form a dense film of crystalline Si. Impurities in the deposited Si film are controlled at low concentrations (both B and P are less than 1 ppm). In the photoelectrochemical measurements, the film shows p-type semiconductor character and large photocurrent. A p–n junction fabricated from the deposited Si film exhibits clear photovoltaic effects. This study represents the first step to the ultimate goal of developing a cost-effective manufacturing process for Si solar cells based on electrodeposition. Creating cheaper solar cells: High-quality Si films for photovoltaic applications were fabricated by electrodeposition from molten CaCl2–CaO–SiO2. Soluble SiIV−O anions generated from solid SiO2 are electrodeposited onto a graphite substrate to form a dense and thick film of p-type Si. Impurities in the deposited Si film are controlled at low concentrations. The film exhibits good photoelectrochemical properties and clear photovoltaic effects.
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Unsymmetrical Biaryl Compounds: Metal- and Reagent-Free Electrochemical Couplings are on the Advance ()
It's electrifying! Electrochemical cross-coupling of aryl compounds provides a one-step approach to unsymmetrical biaryl compounds. A boron-doped diamond electrode is used as the anode to oxidise the phenolic hydroxy group to a phenoxy radical, and 1,1,1,3,3,3-hexafluoroisopropylalcohol (HFIP) and tetraalkylammonium methylsulfate are used as the solvent and electrolyte. Since no reagents are required, no waste is formed from this source.
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A Triple Salting-Out Effect is Required for the Formation of Ionic-Liquid-Based Aqueous Multiphase Systems ()
Novel aqueous multiphase systems (MuPSs) formed by quaternary mixtures composed of cholinium-based ionic liquids (ILs), polymers, inorganic salts, and water are reported herein. The influence of several ILs, polymers, and salts was studied, demonstrating that a triple salting-out is a required phenomenon to prepare MuPSs. The respective phase diagrams and “tie-surfaces” were determined, followed by the evaluation of the effect of temperature. Finally, the remarkable ability of IL-based MuPSs to selectively separate mixtures of textile dyes is shown. Three's a crowd: A simultaneous, triple salting-out effect is required to form ionic-liquid-based three-phase aqueous systems. These novel aqueous multiphase systems (MuPSs) were used for the selective separation of textile dyes, demonstrating their great potential in environmental and industrial applications.
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Magnetless Device for Conducting Three-Dimensional Spin-Specific Electrochemistry ()
Electron spin states play an important role in many chemical processes. Most spin-state studies require the application of a magnetic field. Recently it was found that the transport of electrons through chiral molecules also depends on their spin states and may also play a role in enantiorecognition. Electrochemistry is an important tool for studying spin-specific processes and enantioseparation of chiral molecules. A new device is presented, which serves as the working electrode in electrochemical cells and is capable of providing information on the correlation of spin selectivity and the electrochemical process. The device is based on the Hall effect and it eliminates the need to apply an external magnetic field. Spin-selective electron transfer through chiral molecules can be monitored and the relationship between the enantiorecognition process and the spin of electrons elucidated. Spinmeister: A 3D spin-electrochemistry method enables monitoring of spin-selective electron transfer through chiral molecules. A Hall device incorporated within an electrochemical set-up allows direct measurement of spin polarization in the electrochemical process without the need for a magnetic field.
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Programmable Supra-Assembly of a DNA Surface Adapter for Tunable Chiral Directional Self-Assembly of Gold Nanorods ()
An important challenge in molecular assembly and hierarchical molecular engineering is to control and program the directional self-assembly into chiral structures. Here, we present a versatile DNA surface adapter that can programmably self-assemble into various chiral supramolecular architectures, thereby regulating the chiral directional “bonding” of gold nanorods decorated by the surface adapter. Distinct optical chirality relevant to the ensemble conformation is demonstrated from the assembled novel stair-like and coil-like gold nanorod chiral metastructures, which is strongly affected by the spatial arrangement of neighboring nanorod pair. Our strategy provides new avenues for fabrication of tunable optical metamaterials by manipulating the directional self-assembly of nanoparticles using programmable surface adapters. Coding with DNA: DNA adapters can be programmably assembled into chiral supramolecular architectures following the distinct binding modality enabled by the selective interactions between specific binding domains. Gold nanorods site-specifically decorated on the DNA adapters self-assemble into new plasmonic chiral metastructures with facilely tunable configurations and handedness following the DNA chiral supramolecular matrix.
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Biosynthesis of the Enterotoxic Pyrrolobenzodiazepine Natural Product Tilivalline ()
The nonribosomal enterotoxin tilivalline was the first naturally occurring pyrrolobenzodiazepine to be linked to disease in the human intestine. Since the producing organism Klebsiella oxytoca is part of the intestinal microbiota and the pyrrolobenzodiazepine causes the pathogenesis of colitis it is important to understand the biosynthesis and regulation of tilivalline activity. Here we report the biosynthesis of tilivalline and show that this nonribosomal peptide assembly pathway initially generates tilimycin, a simple pyrrolobenzodiazepine with cytotoxic properties. Tilivalline results from the non-enzymatic spontaneous reaction of tilimycin with biogenetically generated indole. Through a chemical total synthesis of tilimycin we could corroborate the predictions made about the biosynthesis. Production of two cytotoxic pyrrolobenzodiazepines with distinct functionalities by human gut resident Klebsiella oxytoca has important implications for intestinal disease. The Klebsiella oxytoca enterotoxin tilivalline was the first naturally occurring pyrrolobenzodiazepine to be linked to disease in the human intestine. In the biosynthesis of tilivalline the nonribosomal peptide assembly pathway initially generates the cytotoxic pyrrolobenzodiazepine tilimycin. Tilivalline results from the non-enzymatic reaction of tilimycin with biogenetically generated indole.
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P−B Desulfurization: An Enabling Method for Protein Chemical Synthesis and Site-Specific Deuteration ()
Cysteine-mediated native chemical ligation is a powerful method for protein chemical synthesis. Herein, we report an unprecedentedly mild system (TCEP/NaBH4 or TCEP/LiBEt3H; TCEP=tris(2-carboxyethyl)phosphine) for chemoselective peptide desulfurization to achieve effective protein synthesis via the native chemical ligation–desulfurization approach. This method, termed P−B desulfurization, features usage of common reagents, simplicity of operation, robustness, high yields, clean conversion, and versatile functionality compatibility with complex peptides/proteins. In addition, this method can be used for incorporating deuterium into the peptides after cysteine desulfurization by running the reaction in D2O buffer. Moreover, this method enables the clean desulfurization of peptides carrying post-translational modifications, such as phosphorylation and crotonylation. The effectiveness of this method has been demonstrated by the synthesis of the cyclic peptides dichotomin C and E and synthetic proteins, including ubiquitin, γ-synuclein, and histone H2A. An unprecedentedly mild system (TCEP/NaBH4 or TCEP/LiBEt3H; TCEP=tris(2-carboxyethyl)phosphine) for chemoselective peptide desulfurization for effective protein synthesis via the native chemical ligation–desulfurization approach has been developed. This method can be used for incorporating deuterium into the peptides after cysteine desulfurization by running the reaction in D2O buffer.
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Polyion Covalency: Exotic Species from the Unexplored World of Electrostatically Shielded Molecular Ion Chemistry ()
Standard quantum chemical methods have been employed to describe a variety of kinetically stable polyionic molecular species that are trapped in appreciable potential wells by chemical bonding forces, despite powerful electrostatic opposition that challenges conventional chemical detection and characterization. The studied species are covalent or dative analogs of “anti-electrostatic” hydrogen-bonded (AEHB) species, all illustrating how short-range quantum covalency can overcome the powerful “shielding” opposition of long-range electrostatic forces to form highly charged molecular species, analogous to known neutral or singly ionic counterparts. Computational predictions of representative structural, spectroscopic, and NBO-based electronic signatures of multiply charged analogs of common neutral species (CH3CH3, CO2, FeCO) are provided to suggest the unique material properties characteristic of this shielded domain of polyionic chemical phenomena. Anti-electrostatic hydrogen bonds: Kinetically stable polyionic species have been studied by quantum chemical methods. The polyionic species are trapped in potential wells by chemical bonding forces, despite powerful electrostatic opposition that challenges conventional chemical detection and characterization.
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Fast, Efficient and Low E-Factor One-Pot Palladium-Catalyzed Cross-Coupling of (Hetero)Arenes ()
The homocoupling of aryl halides and the heterocoupling of aryl halides with either aryl bromides or arenes bearing an ortho-lithiation directing group are presented. The use of a Pd catalyst, in combination with t-BuLi, allows for the rapid and efficient formation of a wide range of polyaromatic compounds in a one pot procedure bypassing the need for the separate preformation of an organometallic coupling partner. These polyaromatic structures are obtained in high yields, in 10 min at room temperature, with minimal waste generation (E-factors as low as 1.5) and without the need for strict inert conditions, making this process highly efficient and practical in comparison to classical methods. As illustration, several key intermediates of widely used BINOL-derived structures are readily prepared including the highly desired precursor to the chiral TRIP phosphoric acid. Quick-and-clean: The cross-coupling of distinct (hetero)arenes is achieved in a rapid and efficient manner under ambient conditions with very little waste. By using a Pd catalyst and t-BuLi, many polyaromatic compounds are obtained including highly sterically hindered ones. Of these, several are advanced intermediates for widely used chiral Brønsted acid catalysts normally obtained via a rather cumbersome process.
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Induction of Single-Handed Helicity of Polyacetylenes Using Mechanically Chiral Rotaxanes as Chiral Sources ()
Effective induction of preferred-handed helicity of polyacetylenes by pendant mechanically chiral rotaxanes is discussed. Polyacetylenes possessing optically active mechanically chiral rotaxanes in the side chains were synthesized by the polymerization of the corresponding enantiopure [2]rotaxane-type ethynyl monomers prepared by the chiral-phase HPLC separations. The CD Cotton effects revealed that the polyacetylenes took preferred-handed helical conformations depending on the rotaxane chirality. The preferred-handed helix was not disturbed by an additional chiral substituent on the rotaxane side chain. These results demonstrate the significance and utility of mechanically chiral rotaxanes for the effective construction of asymmetric fields. Mechanically chiral compounds are utilized as a chiral source. Polyacetylenes with optically active mechanically chiral rotaxanes in the side chains show strong circular dichroism on the main-chain absorption regions, indicating that the rotaxanes efficiently induce helicity with preferred handedness. These results demonstrate the significance and utility of mechanically chiral rotaxanes for the construction of asymmetric fields.
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Low-Temperature Molten-Salt Production of Silicon Nanowires by the Electrochemical Reduction of CaSiO3 ()
Silicon is an extremely important technological material, but its current industrial production by the carbothermic reduction of SiO2 is energy intensive and generates CO2 emissions. Herein, we developed a more sustainable method to produce silicon nanowires (Si NWs) in bulk quantities through the direct electrochemical reduction of CaSiO3, an abundant and inexpensive Si source soluble in molten salts, at a low temperature of 650 °C by using low-melting-point ternary molten salts CaCl2–MgCl2–NaCl, which still retains high CaSiO3 solubility, and a supporting electrolyte of CaO, which facilitates the transport of O2− anions, drastically improves the reaction kinetics, and enables the electrolysis at low temperatures. The Si nanowire product can be used as high-capacity Li-ion battery anode materials with excellent cycling performance. This environmentally friendly strategy for the practical production of Si at lower temperatures can be applied to other molten salt systems and is also promising for waste glass and coal ash recycling. From old glass to batteries: A new and more sustainable method to produce Si nanowires in bulk quantities through the direct electrochemical reduction of CaSiO3 at a low temperature of 650 °C was developed. The method uses the low-melting-point ternary molten salts of CaCl2–MgCl2–NaCl, which retain high CaSiO3-solubility, and a supporting electrolyte of CaO, which drastically improves the reaction kinetics and enables the electrolysis at low temperatures.
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Semiconductive Copper(I)–Organic Frameworks for Efficient Light-Driven Hydrogen Generation Without Additional Photosensitizers and Cocatalysts ()
As the first example of a photocatalytic system for splitting water without additional cocatalysts and photosensitizers, the comparatively cost-effective Cu2I2-based MOF, Cu-I-bpy (bpy=4,4′-bipyridine) exhibited highly efficient photocatalytic hydrogen production (7.09 mmol g−1 h−1). Density functional theory (DFT) calculations established the electronic structures of Cu-I-bpy with a narrow band gap of 2.05 eV, indicating its semiconductive behavior, which is consistent with the experimental value of 2.00 eV. The proposed mechanism demonstrates that Cu2I2 clusters of Cu-I-bpy serve as photoelectron generators to accelerate the copper(I) hydride interaction, providing redox reaction sites for hydrogen evolution. The highly stable cocatalyst-free and self-sensitized Cu-I-bpy provides new insights into the future design of cost-effective d10-based MOFs for highly efficient and long-term solar fuels production. No additives required: A low-cost Cu2I2-based MOF exhibits efficient photocatalytic H2 production without additional photosensitizers and cocatalysts. DFT calculations reveal a good band alignment with the water redox energy levels. The proposed mechanism demonstrates that Cu2I2 clusters in Cu-I-bpy (bpy=4,4′-bipyridine) serve as photoelectron generators to accelerate copper(I) hydride interaction for hydrogen evolution.
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Flexible Zirconium MOFs as Bromine-Nanocontainers for Bromination Reactions under Ambient Conditions ()
A series of flexible MOFs (PCN-605, PCN-606, and PCN-700) are synthesized and applied to reversible bromine encapsulation and release. The chemical stability of these Zr-MOFs ensures the framework's integrity during the bromine adsorption, while the framework's flexibility allows for structural adaptation upon bromine uptake to afford stronger host–guest interactions and therefore higher bromine adsorption capacities. The flexible MOFs act as bromine-nanocontainers which elongate the storage time of volatile halides under ambient conditions. Furthermore, the bromine pre-adsorbed flexible MOFs can be used as generic bromine sources for bromination reactions giving improved yields and selectivities under ambient conditions when compared with liquid bromine. Bromine that's better than bromine: A series of flexible Zr-based metal–organic frameworks (MOFs) are prepared using a topology guided strategy. During desolvation and bromine adsorption these MOFs undergo significant structural transformations. The bromine pre-adsorbed flexible MOFs are used as generic bromine sources for bromination reactions giving improved yields and selectivities compared to liquid bromine.
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Stereoselective Direct Chlorination of Alkenyl MIDA Boronates: Divergent Synthesis of E and Z α-Chloroalkenyl Boronates ()
The individual molecules of α-chloroalkenyl boronates include both an electrophilic C−Cl bond and a nucleophilic C−B bond, which makes them intriguing organic synthons. Reported herein is a stereodivergent synthesis of both E and Z α-chloroalkenyl N-methyliminodiacetyl (MIDA) boronates through the direct chlorination of alkenyl MIDA boronates using tBuOCl and PhSeCl reagents, respectively. Both reaction processes are stereospecific and the use of sp3-B MIDA boronate is the key contributor to the reactivity. The synthetic value of the boronate products was also demonstrated. One Way or Another: Stereodivergent syntheses of both E and Z α-chloroalkenyl N-methyliminodiacetyl (MIDA) boronates were achieved through the direct chlorination of E-alkenyl MIDA boronates using tBuOCl and PhSeCl reagents, respectively. Both reaction processes are stereospecific and the sp3-B MIDA boronate plays the key role to the reactivity. Broad substrate scope was observed and the synthetic value of the boronate products was demonstrated.
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Influence of Polyethylene Glycol Unit on Palladium- and Nickel-Catalyzed Ethylene Polymerization and Copolymerization ()
The transition-metal-catalyzed copolymerization of olefins with polar functionalized co-monomers represents a major challenge in the field of olefin polymerization. It is extremely difficult to simultaneously achieve improvements in catalytic activity, polar monomer incorporation, and copolymer molecular weight through ligand modifications. Herein we introduce a polyethylene glycol unit to some phosphine-sulfonate palladium and nickel catalysts, and its influence on ethylene polymerization and copolymerization is investigated. In ethylene polymerization, this strategy leads to enhanced activity, catalyst stability, and increased polyethylene molecular weight. In ethylene copolymerization with polar monomers, improvements in all copolymerization parameters are realized. This effect is most significant for polar monomers with hydrogen-bond-donating abilities. PEGged forward: Polyethylene glycol (PEG) substituents are installed in phosphine-sulfonate palladium and nickel catalysts. The polyethylene glycol unit shows beneficial effects in ethylene polymerization and copolymerization reactions.
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A Highly Reactive Oxoiron(IV) Complex Supported by a Bioinspired N3O Macrocyclic Ligand ()
The sluggish oxidants [FeIV(O)(TMC)(CH3CN)]2+ (TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and [FeIV(O)(TMCN-d12)(OTf)]+ (TMCN-d12=1,4,7,11-tetra(methyl-d3)-1,4,7,11-tetraazacyclotetradecane) are transformed into the highly reactive oxidant [FeIV(O)(TMCO)(OTf)]+ (1; TMCO=4,8,12-trimethyl-1-oxa-4,8,12-triazacyclotetradecane) upon replacement of an NMe donor in the TMC and TMCN ligands by an O atom. A rate enhancement of five to six orders of magnitude in both H atom and O atom transfer reactions was observed upon oxygen incorporation into the macrocyclic ligand. This finding was explained in terms of the higher electrophilicity of the iron center and the higher availability of the more reactive S=2 state in 1. This rationalizes nature's preference for using O-rich ligand environments for the hydroxylation of strong C−H bonds in enzymatic reactions. The oxoiron(IV) center in [FeIV(O)(TMCO)(OTf)]+ (TMCO=4,8,12-trimethyl-1-oxa-4,8,12-triazacyclotetradecane; see picture) in an N3O environment exhibits drastically enhanced reactivity relative to the [FeIV(O)(TMC)(CH3CN)]2+ (TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) complex in an N4 environment. This explains nature's preference for using oxygen-rich ligand environments for the hydroxylation of strong C−H bonds.
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Construction of π-Surface-Metalated Pillar[5]arenes which Bind Anions via Anion–π Interactions ()
By simple ligand exchange of the cationic transition-metal complexes [(Cp*)M(acetone)3](OTf)2 (Cp*=pentamethylcyclopentadienyl and M=Ir or Rh) with pillar[5]arene, mono- and polynuclear pillar[5]arenes, a new class of metalated host molecules, is prepared. Single-crystal X-ray analysis shows that the charged transition-metal cations are directly bound to the outer π-surface of aromatic rings of pillar[5]arene. One of the triflate anions is deeply embedded within the cavity of the trinuclear pillar[5]arenes, which is different to the host–guest behavior of most pillar[5]arenes. DFT calculation of the electrostatic potential revealed that the metalated pillar[5]arenes featured an electron-deficient cavity due to the presence of the electron-withdrawing transition metals, thus allowing encapsulation of electron-rich guests mainly driven by anion–π interactions. Cavity filling: A simple yet highly efficient approach gives pillar[5]arene hosts with metalated π-surfaces. The metalated pillar[5]arenes have an electron-deficient cavity owing to the presence of the electron-withdrawing transition-metal moieties, thus allowing the encapsulation of anion guests via anion–π interactions.
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Versatile Tri(pyrazolyl)phosphanes as Phosphorus Precursors for the Synthesis of Highly Emitting InP/ZnS Quantum Dots ()
Tri(pyrazolyl)phosphanes (5R1,R2) are utilized as an alternative, cheap and low-toxic phosphorus source for the convenient synthesis of InP/ZnS quantum dots (QDs). From these precursors, remarkably long-term stable stock solutions (>6 months) of P(OLA)3 (OLAH=oleylamine) are generated from which the respective pyrazoles are conveniently recovered. P(OLA)3 acts simultaneously as phosphorus source and reducing agent in the synthesis of highly emitting InP/ZnS core/shell QDs. These QDs are characterized by a spectral range between 530–620 nm and photoluminescence quantum yields (PL QYs) between 51–62 %. A proof-of-concept white light-emitting diode (LED) applying the InP/ZnS QDs as a color-conversion layer was built to demonstrate their applicability and processibility. Taking stock: Tri(pyrazolyl)phosphanes are utilized as a less-toxic P1 source for the synthesis of long-term stable stock solutions of P(OLA)3 (OLAH=oleylamine). The stock solutions are used for the preparation of InP/ZnS quantum dots emitting in the spectral range between 530–620 nm with photoluminescence quantum yields between 51–62 %. The liberated pyrazoles can easily be recovered and reused.
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Pnictogen (As, Sb, Bi) Nanosheets for Electrochemical Applications Are Produced by Shear Exfoliation Using Kitchen Blenders ()
Group 5 elements (pnictogens) are attracting attention as mono-elemental 2D materials with semiconducting properties. In their Communication (DOI: 10.1002/anie.201706389), M. Pumera et al. present a green, scalable method for the aqueous shear-force exfoliation of pnictogens using household kitchen blenders. The exfoliated nanosheets were evaluated in water-splitting reactions, in which Sb showed the best performance. These results are significant for future electrochemical applications of pnictogens.
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Unlocking the Electrocatalytic Activity of Antimony for CO2 Reduction by Two-Dimensional Engineering of the Bulk Material ()
Two-dimensional (2D) materials are known to be useful in catalysis. Engineering 3D bulk materials into the 2D form can enhance the exposure of the active edge sites, which are believed to be the origin of the high catalytic activity. Reported herein is the production of 2D “few-layer” antimony (Sb) nanosheets by cathodic exfoliation. Application of this 2D engineering method turns Sb, an inactive material for CO2 reduction in its bulk form, into an active 2D electrocatalyst for reduction of CO2 to formate with high efficiency. The high activity is attributed to the exposure of a large number of catalytically active edge sites. Moreover, this cathodic exfoliation process can be coupled with the anodic exfoliation of graphite in a single-compartment cell for in situ production of a few-layer Sb nanosheets and graphene composite. The observed increased activity of this composite is attributed to the strong electronic interaction between graphene and Sb. Less is more: By engineering bulk antimony using an electrochemical exfoliation method, two-dimensional antimony nanosheets and their composite with graphene were formed. The electrocatalytic activity of these two materials towards reducing CO2 to formate were evaluated, thus showing that the materials were more active than bulk antimony.
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Edith Flanigen Award for Jovana Zečević / Hamburger Wissenschaftspreis for Xinliang Feng and Klaus Müllen / And also in the News ()

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Authors Profile ()

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Analytical Description of NMR Relaxation Highlights Correlated Dynamics in Intrinsically Disordered Proteins ()
The potential energy landscapes of intrinsically disordered proteins are remarkably flat compared their folded counterparts, making their functional modes difficult to study. In their Communication (DOI: 10.1002/anie.201706740), M. Blackledge and co-workers use a combination of high-resolution NMR spectroscopy and advanced molecular dynamics simulation to investigate the extent of functionally important correlated motions in this essential class of proteins.
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Noncovalent Functionalization and Charge Transfer in Antimonene ()
Antimonene, a novel group 15 two-dimensional material, is functionalized with a tailormade perylene bisimide through strong van der Waals interactions. The functionalization process leads to a significant quenching of the perylene fluorescence, and surpasses that observed for either graphene or black phosphorus, thus allowing straightforward characterization of the flakes by scanning Raman microscopy. Furthermore, scanning photoelectron microscopy studies and theoretical calculations reveal a remarkable charge-transfer behavior, being twice that of black phosphorus. Moreover, the excellent stability under environmental conditions of pristine antimonene has been tackled, thus pointing towards the spontaneous formation of a sub-nanometric oxide passivation layer. DFT calculations revealed that the noncovalent functionalization of antimonene results in a charge-transfer band gap of 1.1 eV. Flake off: Reported for the first time is the noncovalent functionalization of antimonene using perylene bisimides (PDI). The significant quenching of the fluorescence of the PDI allows straightforward characterization of the antimonene flakes deposited on Si/SiO2 substrates. This work paves the way for the development of novel applications based on antimonene by tailoring its electronic properties.
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Docking of Antibodies into the Cavities of DNA Origami Structures ()
Immobilized antibodies are extensively employed for medical diagnostics, such as in enzyme-linked immunosorbent assays. Despite their widespread use, the ability to control the orientation of immobilized antibodies on surfaces is very limited. Herein, we report a method for the covalent and orientation-selective immobilization of antibodies in designed cavities in 2D and 3D DNA origami structures. Two tris(NTA)-modified strands are inserted into the cavity to form NTA–metal complexes with histidine clusters on the Fc domain. Subsequent covalent linkage to the antibody was achieved by coupling to lysine residues. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) confirmed the efficient immobilization of the antibodies in the origami structures. This increased control over the orientation of antibodies in nanostructures and on surfaces has the potential to direct the interactions between antibodies and targets and to provide more regular surface assemblies of antibodies. Fits like a glove: Antibodies are immobilized in the cavities of a DNA origami structure by chelation to metal complexes at each side of the cavity and by covalent coupling to activated esters inside the cavity.
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Cove-Edge Nanoribbon Materials for Efficient Inverted Halide Perovskite Solar Cells ()
Two cove-edge graphene nanoribbons hPDI2-Pyr-hPDI2 (1) and hPDI3-Pyr-hPDI3 (2) are used as efficient electron-transporting materials (ETMs) in inverted planar perovskite solar cells (PSCs). Devices based on the new graphene nanoribbons exhibit maximum power-conversion efficiencies (PCEs) of 15.6 % and 16.5 % for 1 and 2, respectively, while a maximum PCE of 14.9 % is achieved with devices based on [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM). The interfacial effects induced by these new materials are studied using photoluminescence (PL), and we find that 1 and 2 act as efficient electron-extraction materials. Additionally, compared with PC61BM, these new materials are more hydrophobic and have slightly higher LUMO energy levels, thus providing better device performance and higher device stability. Blue (nano)ribbon solar cells: Two electron-deficient graphene nanoribbons are used as the electron-transporting materials (ETMs) in inverted perovskite solar cells (PSCs). The nanoribbons provide improved performance over the commonly used PC61BM. The most important benefits are the improved PCE (>10 % over PC61BM) and improved device lifetime owing to the hydrophobic nature of the solubilizing chains on the ribbons.
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Morphology-Dependent Cell Imaging by Using a Self-Assembled Diacetylene Peptide Amphiphile ()
Herein, a novel cationic peptide gemini amphiphile containing diacetylene motifs (DA2P) is presented, which self-assembles into novel tadpole- and bola-shaped nanostructures at low concentrations and nanofibers at higher concentrations. Interestingly, the DA2P assemblies can be polymerized into a fluorescent red phase but only during incubation with HeLa cells, most likely owing to the reorganization of the diacetylene chains of DA2P upon interaction with the cell membrane. The red-fluorescent polymerized DA2P assemblies can serve as a novel cell imaging probe. However, only vesicles, tadpole- and bola-shaped DA2P assemblies can be translocated into HeLa cells, whereas the nanofiber-like DA2P assemblies are trapped by the cell membranes and do not enter the cells. Hence, morphology-dependent cell imaging is observed. Novel nanostructure: A peptide gemini amphiphile containing diacetylene motifs self-assembles into novel tadpole- and bola-shaped nanostructures at low concentrations, as well as nanofibers at higher concentrations. Interestingly, morphology-dependent cell imaging is achieved owing to the polymerization of the diacetylenes upon interaction with the cell membrane.
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Intrinsic Broadband White-Light Emission from Ultrastable, Cationic Lead Halide Layered Materials ()
We report a family of cationic lead halide layered materials, formulated as [Pb2X2]2+[−O2C(CH)2CO2−] (X=F, Cl, Br), exhibiting pronounced broadband white-light emission in bulk form. These well-defined PbX-based structures achieve an external quantum efficiency as high as 11.8 %, which is comparable to the highest reported value (ca.9 %) for broadband phosphors based on layered organolead halide perovskites. More importantly, our cationic materials are ultrastable lead halide materials, which overcome the air/moisture-sensitivity problems of lead perovskites. In contrast to the perovskites and other bulk emitters, the white-light emission intensity of our materials remains undiminished after continuous UV irradiation for 30 days under atmospheric conditions (ca.60 % relative humidity). Our mechanistic studies confirm that the broadband emission is ascribed to short-range electron-phonon coupling in the strongly deformable lattice and generated self-trapped carriers. White out: Cationic lead halide layered materials formulated as [Pb2X2]2+[−O2C(CH)2CO2−] (X=F, Cl, Br) are ultrastable, broadband white-light emitters with an external quantum efficiency as high as 11.8 % and long-term photostability under atmospheric conditions, which overcome the air/moisture-sensitivity problems of lead perovskites.
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High-Temperature Formation of a Functional Film at the Cathode/Electrolyte Interface in Lithium–Sulfur Batteries: An In Situ AFM Study ()
Lithium–sulfur (Li–S) batteries have been attracting wide attention for their promising high specific capacity. A deep understanding of Li–S interfacial mechanism including the temperature (T) effect is required to meet the demands for battery modification and systematic study. Herein, the interfacial behavior during discharge/charge is investigated at high temperature (HT) of 60 °C in an electrolyte based on lithium bis(fluorosulfonyl) imide (LiFSI). By in situ atomic force microscopy (AFM), dynamic evolution of insoluble Li2S2 and Li2S is studied at the nanoscale. An in situ formed functional film can be directly monitored at 60 °C after Li2S nucleation. It retards side reactions and facilitates interfacial redox. The insight into the interfacial processes at HT provides direct evidence of the existence of the film and reveals its dynamic behavior, providing a new avenue for electrolyte design and performance enhancement. Caught on film: By electrochemical AFM investigation at 60 °C, in situ formation of a functional film can be directly monitored at a highly oriented pyrolytic graphite (HOPG) cathode/polysulfide electrolyte interface in Li–S batteries. The film forms by a LiF net capturing polysulfide (PS) intermediates by both physical confinement and chemical anchoring effects.
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Asymmetric Cycloisomerization of o-Alkenyl-N-Methylanilines to Indolines by Iridium-Catalyzed C(sp3)−H Addition to Carbon–Carbon Double Bonds ()
Highly enantioselective cycloisomerization of N-methylanilines, bearing o-alkenyl groups, into indolines is established. An iridium catalyst bearing a bidentate chiral diphosphine effectively promotes the intramolecular addition of the C(sp3)−H bond across a carbon–carbon double bond in a highly enantioselective fashion. The reaction gives indolines bearing a quaternary stereogenic carbon center at the 3-position. The reaction mechanism involves rate-determining oxidative addition of the N-methyl C−H bond, followed by intramolecular carboiridation and subsequent reductive elimination. Build a bridge: Highly enantioselective cycloisomerization of N-methylanilines, bearing o-alkenyl groups, into indolines was established. An iridium catalyst bearing a bidentate chiral diphosphine effectively promotes the intramolecular addition of the C(sp3)−H bond across a C=C bond in an enantioselective fashion. The reaction gives indolines bearing a quaternary stereogenic carbon center at the 3-position.
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Medium-Sized-Ring Analogues of Dibenzodiazepines by a Conformationally Induced Smiles Ring Expansion ()
Analogues of dibenzodiazepines, in which the seven-membered nitrogen heterocycle is replaced by a 9–12-membered ring, were made by an unactivated Smiles rearrangement of five- to eight-membered heterocyclic anthranilamides. The conformational preference of the tertiary amide in the starting material leads to intramolecular migration of a range of aryl rings, even those lacking electron-withdrawing activating groups, and provides a method for nn+4 ring expansion. The medium-ring products adopt a chiral ground state with an intramolecular, transannular hydrogen bond. The rate of interconversion of their enantiomeric conformers depends on solvent polarity. Ring size and adjacent steric hindrance modulate this hidden hydrophilicity, thus making this scaffold a good candidate for drug development. Smiles rearrangement of readily prepared amide derivatives of benzo-fused nitrogen heterocycles requires no electronic activation to give medium-sized-ring analogues of the dibenzodiazepine tricyclic antidepressants.⋅The reaction tolerates electron-rich and electron-poor rings, delivers 9-12-membered rings, and leads to conformationally restricted products
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Chemistry / Physiology or Medicine, and Physics ()

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An Eighteen-Membered Macrocyclic Ligand for Actinium-225 Targeted Alpha Therapy ()
The 18-membered macrocycle H2macropa was investigated for 225Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all 225Ac (26 kBq) in 5 min at RT. [225Ac(macropa)]+ remained intact over 7 to 8 days when challenged with either excess La3+ ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled 225Ac in just minutes at RT, and macropa-Tmab retained >99 % of its 225Ac in human serum after 7 days. In LNCaP xenograft mice, 225Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free 225Ac over 96 h. These findings establish macropa to be a highly promising ligand for 225Ac chelation that will facilitate the clinical development of 225Ac TAT for the treatment of soft-tissue metastases. Actinium in action! A macrocyclic ligand exhibits unprecedented radiolabeling efficiency for the large α-emitting radionuclide 225Ac3+. This ligand is extremely promising for the implementation of 225Ac in targeted alpha therapy for cancer. RCY=radiochemical yield.
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Synthesis of Biphenylenes and Their Higher Homologues by Cyclization of Aryne Derivatives ()
This investigation demonstrates that a series of biphenylenes can be easily prepared from their corresponding halobiphenyls by the cyclization of in situ generated 2′,3′-didehydro-2-lithiobiphenyls at low temperature. Two remarkable advantages of this synthetic method include 1) the lack of any need for transition-metal catalysts or reagents in the cyclization, and 2) the ability to obtain C1-functionalized products by treating the reaction intermediate 1-lithiobiphenylene with an electrophilic reagent. π-Extended derivatives, such as benzobiphenylenes, dibenzobiphenylene, linear/angular [3]phenylenes, and biphenyleno[2,3-b]biphenylenes, were synthesized similarly using suitable biaryls or teraryls. Biphenylenes can be easily and efficiently obtained at low temperature by the organolithium-mediated cyclization of halobiphenyls via an aryne intermediate. This synthetic protocol provides an advantage for the direct and controlled functionalization at the C1 position.
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Cover Picture: A Pyrene-Linked Cavity within a β-Barrel Protein Promotes an Asymmetric Diels–Alder Reaction (Angew. Chem. Int. Ed. 44/2017) ()
A pyrene-linked protein cavity attracts two substrate molecules like the scent of a flower attracts butterflies. In their Communication on page 13618 ff., A. Onoda, T. Hayashi, and co-workers demonstrate that a polycyclic pyrene moiety linked within the rigid protein scaffold of the β-barrel of nitrobindin acts as a platform to provide an aromatic interaction with a substrate. An asymmetric Diels–Alder reaction between azachalcone and cyclopentadiene proceeds smoothly with high stereoselectivity within the reaction scaffold.
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Inside Cover: Precisely Assembled Cyclic Gold Nanoparticle Frames by 2D Polymer Single-Crystal Templating (Angew. Chem. Int. Ed. 44/2017) ()
Free-standing frames can be prepared by a directed assembly method in which nanoparticles are precisely linked together by using polymer single crystals (PSCs) as a template. In their Communication on page 13645 ff., C. Y. Li and co-workers use preformed PSCs to direct the crystallization of block copolymers, which in turn direct gold NPs (AuNPs) to form precisely controlled AuNP frames. These AuNP frames topologically resemble nanoparticle rings and cyclic polymer chains, and show unique surface plasmon resonance behaviors.
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Inside Back Cover: Olefins from Natural Gas by Oxychlorination (Angew. Chem. Int. Ed. 44/2017) ()
Turning myth into reality. Pérez-Ramírez et al. show in their Communication on page 13670 ff. the outstanding performance of EuOCl for the production of light olefins from ethane and propane by oxychlorination chemistry. The high activity, selectivity, and stability of the system are illustrated by the mythological princess Europa, who was carried from Asia to the Hellenic world by Zeus, who was disguised as a white bull. Both the continent of Europe and the element europium later took her name.
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Back Cover: Potential-Cycling Synthesis of Single Platinum Atoms for Efficient Hydrogen Evolution in Neutral Media (Angew. Chem. Int. Ed. 44/2017) ()
Single Pt atoms can be synthesized on CoP-based nanotube arrays supported by Ni foams through potential cycling. In their Communication on page 13694 ff., X. J. Liu, J. Luo, and co-workers use this strategy to transfer single Pt atoms from a Pt source to a nanotube substrate in a neutral phosphate buffer solution (PBS). As an electrocatalyst for the hydrogen evolution reaction (HER) in PBS, these single atoms exhibit a higher Pt-mass activity and a better stability than commercial Pt/CIn.
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Frontispiece: Because the Light is Better Here: Correlation-Time Analysis by NMR Spectroscopy ()
NMR Spectroscopy In their Communication on page 13590, M. Ernst, B. H. Meier, and A. A. Smith examine potential pitfalls for the NMR analysis of protein dynamics and propose the use of dynamics detectors to characterize different ranges of correlation times.
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Graphical Abstract: Angew. Chem. Int. Ed. 44/2017 ()

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Spotlights on our sister journals: Angew. Chem. Int. Ed. 44/2017 ()

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Yasujiro Murata ()
“If I were a car I would be a red Porsche 911. If I could be anyone for a day, I would be the conductor of an orchestra ...” This and more about Yasujiro Murata can be found on page 13562.
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Società Chimica Italiana Medals 2017 ()

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Enantioselective [2,3]-Sigmatropic Rearrangements: Metal-Bound or Free Ylides as Reaction Intermediates? ()
Out of bounds: Enantioselective rearrangement reactions are a long-standing challenge in organic synthesis. Recent advances are highlighted that led to the development of the first enantioselective Doyle–Kirmse reaction and enantioselective rearrangement reactions of iodonium ylides.
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Expanding the Structural Space of Ribosomal Peptides: Autocatalytic N-Methylation in Omphalotin Biosynthesis ()
Tail-Me: The N-methylation of backbone amide bonds in peptide natural products was thought to be exclusive to non-ribosomal peptides. A newly discovered methylation mechanism now brings this structural feature into the world of ribosomal peptides, thereby significantly expanding the structural diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs).
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Cascades in Compartments: En Route to Machine-Assisted Biotechnology ()
Biological compartmentalization is a fundamental principle of life that allows cells to metabolize, propagate, or communicate with their environment. Much research is devoted to understanding this basic principle and to harness biomimetic compartments and catalytic cascades as tools for technological processes. This Review summarizes the current state-of-the-art of these developments, with a special emphasis on length scales, mass transport phenomena, and molecular scaffolding approaches, ranging from small cross-linkers over proteins and nucleic acids to colloids and patterned surfaces. We conclude that the future exploration and exploitation of these complex systems will largely benefit from technical solutions for the integrated, machine-assisted development and maintenance of a next generation of biotechnological processes. These goals should be achievable by implementing microfluidics, robotics, and added manufacturing techniques supplemented by theoretical simulations as well as computer-aided process modeling based on big data obtained from multiscale experimental analyses. Machine-generated multienzyme cascades: The machine-assisted development of biomimetic compartments and catalytic cascades will pave the way towards a novel generation of biotechnological processes. Molecular scaffolds with small cross-linkers, proteins, nucleic acids, colloids, and patterned surfaces can be used to arrange the catalytic units. S: substrate, P: product.
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Because the Light is Better Here: Correlation-Time Analysis by NMR Spectroscopy ()
Relaxation data in NMR spectra are often used for dynamics analysis, by modeling motion in the sample with a correlation function consisting of one or more decaying exponential terms, each described by an order parameter, and a correlation time. This method has its origins in the Lipari–Szabo model-free approach, which originally considered overall tumbling plus one internal motion and was later expanded to several internal motions. Considering several of these cases in the solid state it is found that if the real motion is more complex than the assumed model, model fitting is biased towards correlation times where the relaxation data are most sensitive. This leads to unexpected distortions in the resulting dynamics description. Therefore dynamics detectors should be used, which characterize different ranges of correlation times and can help in the analysis of protein motion without assuming a specific model of the correlation function. Fighting bias: NMR Dynamics data are more sensitive to some correlation times than to others. Models of the correlation function tend to be biased towards where the light is better, that is, where the experiment is more sensitive, thereby yielding an unreliable characterization of the motion. Replacing modeling by detectors that are sensitive to different ranges of correlation times could help to overcome this bias.
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Enzyme Activity by Design: An Artificial Rhodium Hydroformylase for Linear Aldehydes ()
Artificial metalloenzymes (ArMs) are hybrid catalysts that offer a unique opportunity to combine the superior performance of natural protein structures with the unnatural reactivity of transition-metal catalytic centers. Therefore, they provide the prospect of highly selective and active catalytic chemical conversions for which natural enzymes are unavailable. Herein, we show how by rationally combining robust site-specific phosphine bioconjugation methods and a lipid-binding protein (SCP-2L), an artificial rhodium hydroformylase was developed that displays remarkable activities and selectivities for the biphasic production of long-chain linear aldehydes under benign aqueous conditions. Overall, this study demonstrates that judiciously chosen protein-binding scaffolds can be adapted to obtain metalloenzymes that provide the reactivity of the introduced metal center combined with specifically intended product selectivity. Artificial metalloenzymes are hybrid catalysts that offer a unique opportunity to combine the superior performance of natural protein structures with the unnatural reactivity of transition-metal catalytic centers. An artificial rhodium hydroformylase has been developed that displays remarkable activities and selectivities in the biphasic production of long-chain linear aldehydes.
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Regioselective Transformation of Long π-Conjugated Backbones: From Oligofurans to Oligoarenes ()
We demonstrate the transformation of oligofurans through sequential Diels–Alder cycloaddition reactions to provide oligoarenes in two chemical steps, regardless of the oligomer length. By this method, oligonaphthalenes containing up to six units were obtained in high yield through the formation of up to 12 new C−C bonds. The versatility of this method was demonstrated for various polyaromatic hydrocarbons. The regioselectivity of this process enabled the synthesis of a library of substituted triarylenes from a single terfuran precursor by modification of the dienophile strength and the order of addition. Overall, this study demonstrates that long oligofurans are interesting not only as organic electronic materials, but also as starting materials for the formation of various conjugated systems. To cut a long story short: Oligofurans underwent sequential Diels–Alder reactions to provide oligoarenes in two chemical steps, regardless of the oligomer length (see picture). Different maleimide and benzyne dienophiles were also used to construct a range of substituted oligoarenes from a single oligofuran precursor in a highly regioselective manner.
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Manipulation of Biomolecule-Modified Liquid-Metal Blobs ()
Soft and deformable liquid metals (LMs) are building components in various systems related to uncertain and dynamic task environments. Herein we describe the development of a biomolecule-triggered external-manipulation method involving LM conjugates for the construction of future innovative soft robotics operating in physiological environments. Functional soft hybrids composed of a liquid-metal droplet, a thiolated ligand, and proteins were synthesized for the expression of diverse macroscopic commands, such as attachment to cells, binary fusion, and self-propelled movement through molecular recognition and enzymatic reactions. Our technology could be used to create new state-of-the-art soft robots for chemical and biomedical engineering applications. No interest in blobbing out: Biomolecule-functionalized liquid-metal (LM) blobs (see picture) were developed with macroscopic behavior promoted by molecular recognition, for example, through formation of the biotin–avidin complex. Bubble formation on the surface of enzyme-modified LM conjugates also enabled self-propelled dynamic motion. These behaviors could lead to efficient LM soft robots for operation in physiological environments.
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Combining Orthogonal Chain-End Deprotections and Thiol–Maleimide Michael Coupling: Engineering Discrete Oligomers by an Iterative Growth Strategy ()
Orthogonal maleimide and thiol deprotections were combined with thiol–maleimide coupling to synthesize discrete oligomers/macromolecules on a gram scale with molecular weights up to 27.4 kDa (128mer, 7.9 g) using an iterative exponential growth strategy with a degree of polymerization (DP) of 2n−1. Using the same chemistry, a “readable” sequence-defined oligomer and a discrete cyclic topology were also created. Furthermore, uniform dendrons were fabricated using sequential growth (DP=2n−1) or double exponential dendrimer growth approaches (DP=22n −1) with significantly accelerated growth rates. A versatile, efficient, and metal-free method for construction of discrete oligomers with tailored structures and a high growth rate would greatly facilitate research into the structure–property relationships of sophisticated polymeric materials. Discrete oligomers were fabricated by a versatile, efficient, and metal-free chemical process, which combines orthogonal deprotections of maleimide and thiol groups together with thiol–maleimide Michael coupling. Key: iterative exponential growth (IEG); double exponential dendrimer growth (DEDG); degree of polymerization (DP).
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A Pyrene-Linked Cavity within a β-Barrel Protein Promotes an Asymmetric Diels–Alder Reaction ()
A unique π-expanded reaction cavity tethering a polycyclic moiety which provides a platform for substrate binding was constructed within the robust β-barrel structure of nitrobindin (NB). NB variants with cavities of different sizes and shapes are coupled with N-(1-pyrenyl)maleimide (Pyr) to prepare a series of NB-Pyr conjugates. The orientation of the pyrene moiety is fixed within the cavity by the coupling reaction. The fluorescent quenching analysis of NB-Pyr indicates that azachalcone (aza), which is a dienophile for a Diels–Alder (DA) reaction, is efficiently incorporated within the pyrene-linked reaction cavity by the aromatic interaction. The DA reaction between aza and cyclopentadiene proceeds within the reaction cavity of NB-Pyr in the presence of CuII ion in high yield and high enantio- and regioselectivity. Selectivity by the barrel-load: A reaction cavity with a tethered polycyclic pyrene moiety, which acts as a platform to provide aromatic interactions, is constructed within the rigid scaffold of the β-barrel nitrobindin protein. An asymmetric Diels–Alder reaction between azachalcone and cyclopentadiene proceeds within the reaction cavity of the pyrene-linked nitrobindin with high stereoselectivity.
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Peristome-Mimetic Curved Surface for Spontaneous and Directional Separation of Micro Water-in-Oil Drops ()
Separation of micro-scaled water-in-oil droplets is important in environmental protection, bioassays, and saving functional inks. So far, bulk oil–water separation has been achieved by membrane separation and sponge absorption, but micro-drop separation still remains a challenge. Herein we report that instead of the “plug-and-go” separation model, tiny water-in-oil droplets can be separated into pure water and oil droplets through “go-in-opposite ways” on curved peristome-mimetic surfaces, in milliseconds, without energy input. More importantly, this overflow controlled method can be applied to handle oil-in-oil droplets with surface tension differences as low as 14.7 mN m−1 and viscous liquids with viscosities as high as hundreds centipoises, which markedly increases the range of applicable liquids for micro-scaled separation. Furthermore, the curved peristome-mimetic surface guides the separated drops in different directions with high efficiency. Keep 'em separated: A curved surface resembling the peristome, that is, the fringe of small projections around the opening of a capsule of a tropical pitcher plant is prepared. It enables the spontaneous separation of water and oil from micro-scale water-in-oil drops without energy input. The separation occurs within milliseconds and the separated liquids are spontaneously and uni-directionally transported in different directions.
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An Extensive Family of Heterometallic Titanium(IV)–Metal(III) Rings with Structure Control through Templates ()
A family of heterometallic [Cat][TixMO(x+1)(O2CtBu)2x+2] rings is reported where Cat=a secondary or tertiary alkyl ammonium ion, x=7, 8 or 9, and M=FeIII, GaIII, CrIII, InIII and AlIII. The structures are regular polygons with eight, nine or ten vertices with each edge bridged by an oxide and two pivalates. The size of the ring formed is controlled by the alkylammonium cation present. In each case a homometallic by-product is found [Cat][TixO(x+1)(O2CtBu)2x−1]. Size control: A family of heterometallic [Cat][TixMO(x+1)(O2C tBu)2x+2] rings is reported where Cat=a secondary or tertiary alkyl ammonium ion, x=7, 8 or 9, and M=Fe, Ga, Cr, In and Al. The structures are regular polygons with eight, nine or ten vertices with each edge bridged by an oxide and two pivalates. The size of the ring formed is controlled by the alkylammonium cation present.
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AFM Imaging of Hybridization Chain Reaction Mediated Signal Transmission between Two DNA Origami Structures ()
Signal transfer is central to the controlled exchange of information in biology and advanced technologies. Therefore, the development of reliable, long-range signal transfer systems for artificial nanoscale assemblies is of great scientific interest. We have designed such a system for the signal transfer between two connected DNA nanostructures, using the hybridization chain reaction (HCR). Two sets of metastable DNA hairpins, one of which is immobilized at specific points along tracks on DNA origami structures, are polymerized to form a continuous DNA duplex, which is visible using atomic force microscopy (AFM). Upon addition of a designed initiator, the initiation signal is efficiently transferred more than 200 nm from a specific location on one origami structure to an end point on another origami structure. The system shows no significant loss of signal when crossing from one nanostructure to another and, therefore, has the potential to be applied to larger multi-component DNA assemblies. Molecular domino chain reaction: The hybridization chain reaction (HCR) between metastable DNA hairpins is immobilized on a DNA origami structure and implemented for signal transfer across two DNA origami structures.
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Engineered Fluorine Metabolism and Fluoropolymer Production in Living Cells ()
Fluorine has become an important element for the design of synthetic molecules for use in medicine, agriculture, and materials. Despite the many advantages provided by fluorine for tuning key molecular properties, it is rarely found in natural metabolism. We seek to expand the molecular space available for discovery through the development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, we engineered a microbial host for organofluorine metabolism and show that we can achieve the production of the fluorinated diketide 2-fluoro-3-hydroxybutyrate at approximately 50 % yield. This fluorinated diketide can be used as a monomer in vivo to produce fluorinated poly(hydroxyalkanoate) (PHA) bioplastics with fluorine substitutions ranging from around 5–15 %. This system provides a platform to produce mm flux through the key fluoromalonyl coenzyme A (CoA) building block, thereby offering the potential to generate a broad range of fluorinated small-molecule targets in living cells. Live action: An engineered microbial host for organofluorine metabolism can produce a fluorinated diketide at around 50 % yield. The diketide can be used as a monomer to produce fluorinated poly(hydroxyalkanoate) bioplastics in vivo with fluorine substitution of up to 15 %. This system provides a platform to generate a broad range of fluorinated small-molecule targets in living cells.
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Phosphate Transfer in Activated Protein Complexes Reveals Interaction Sites ()
For many proteins, phosphorylation regulates their interaction with other biomolecules. Herein, we describe an unexpected phenomenon whereby phosphate groups are transferred non-enzymatically from one interaction partner to the other within a binding interface upon activation in the gas phase. Providing that a high affinity exists between the donor and acceptor sites, this phosphate transfer is very efficient and the phosphate groups only ligate to sites in proximity to the binding region. Consequently, such phosphate-transfer reactions may define with high precision the binding site between a phosphoprotein and its binding partner, as well as reveal that the binding site in this system is retained in the phase transfer from solution to the gas phase. Pass the P: Phosphate groups can be transferred non-enzymatically from one interaction partner to the other during gas-phase activation. In high-affinity complexes, this phosphate transfer occurs within the binding site, thereby revealing the interaction interface within the protein/phosphopeptide complex.
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Precisely Assembled Cyclic Gold Nanoparticle Frames by 2D Polymer Single-Crystal Templating ()
In recent decades, extensive studies have been devoted to assembling nanoparticles (NPs) into various ordered structures to achieve novel optical properties. However, it still remains a challenging task to assemble NPs into cyclic one-dimensional (1D) shapes, such as rings and frames. Herein, we report a directed assembly method to precisely assemble NPs into well-defined, free-standing frames using polymer single crystals (PSCs) as the template. Preformed poly(ethylene oxide) (PEO) single crystals were used as the template to direct the crystallization of block copolymer (BCP) poly(ethylene oxide)-b-poly(4-vinylpyridine) (PEO-b-P4VP), which directs the gold NPs (AuNPs) to form AuNP frames. By controlling the PSC growth, we were able to, for the first time, precisely tune both the size and width of the AuNP frame. These novel AuNP frames topologically resemble NP nanorings and cyclic polymer chains, and show unique surface plasmon resonance (SPR) behaviors. Frame: Free-standing gold nanoparticle (AuNP) frame structures are formed by directed assembly of AuNPs on polymer single-crystal templates. The size and width of the frames are precisely controllable and easily tunable. These frames resemble NP nanorings and 1D cyclic polymer chains, and have intriguing optical properties similar to Au nanorods.
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High-Performance CsPb1−xSnxBr3 Perovskite Quantum Dots for Light-Emitting Diodes ()
All inorganic CsPbBr3 perovskite quantum dots (QDs) are potential emitters for electroluminescent displays. We have developed a facile hot-injection method to partially replace the toxic Pb2+ with highly stable Sn4+. Meanwhile, the absolute photoluminescence quantum yield of CsPb1−xSnxBr3 increased from 45 % to 83 % with SnIV substitution. The transient absorption (TA) exciton dynamics in undoped CsPbBr3 and CsPb0.67Sn0.33Br3 QDs at various excitation fluences were determined by femtosecond transient absorption, time-resolved photoluminescence, and single-dot spectroscopy, providing clear evidence for the suppression of trion generation by Sn doping. These highly luminescent CsPb0.67Sn0.33Br3 QDs emit at 517 nm. A device based on these QDs exhibited a luminance of 12 500 cd m−2, a current efficiency of 11.63 cd A−1, an external quantum efficiency of 4.13 %, a power efficiency of 6.76 lm w−1, and a low turn-on voltage of 3.6 V, which are the best values among reported tin-based perovskite quantum-dot LEDs. Suppressed trion formation: CsPb1−xSnxBr3 quantum dots (QDs) were synthesized by a hot-injection approach. As trion formation is suppressed by the SnIV substitution, light-emitting diodes (LEDs) based on these highly luminescent QDs performed very well, with the highest current efficiencies and external quantum efficiencies ever reported for such Sn-based systems.
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Gas-Phase Synthesis of the Elusive Cyclooctatetraenyl Radical (C8H7) via Triplet Aromatic Cyclooctatetraene (C8H8) and Non-Aromatic Cyclooctatriene (C8H8) Intermediates ()
The 1,2,4,7-cyclooctatetraenyl radical (C8H7) has been synthesized for the very first time via the bimolecular gas-phase reaction of ground-state carbon atoms with 1,3,5-cycloheptatriene (C7H8) on the triplet surface under single-collision conditions. The barrier-less route to the cyclic 1,2,4,7-cyclooctatetraenyl radical accesses exotic reaction intermediates on the triplet surface, which cannot be synthesized via classical organic chemistry methods: the triplet non-aromatic 2,4,6-cyclooctatriene (C8H8) and the triplet aromatic 1,3,5,7-cyclooctatetraene (C8H8). Our approach provides a clean gas-phase synthesis of this hitherto elusive cyclic radical species 1,2,4,7-cyclooctatetraenyl via a single-collision event and opens up a versatile, unconventional path to access this previously largely obscure class of cyclooctatetraenyl radicals, which have been impossible to access through classical synthetic methods. Carbon eight-ed: Gas-phase reaction of ground-state carbon atoms and cycloheptatriene (C7H8) under single-collision conditions leads to the production of the 1,2,4,7-cyclooctatetraenyl radical (C8H7). Ab initio electronic structure calculation shows the reaction proceeds via exotic triplet C8H8 reaction intermediates: the non-aromatic 2,4,6-cyclooctatriene and the aromatic 1,3,5,7-cyclooctatetraene. The picture shows the flux contour map of the reaction.
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Manganese Dioxide Nanozymes as Responsive Cytoprotective Shells for Individual Living Cell Encapsulation ()
A powerful individual living cell encapsulation strategy for long-term cytoprotection and manipulation is reported. It uses manganese dioxide (MnO2) nanozymes as intelligent shells. As expected, yeast cells can be directly coated with continuous MnO2 shells via bio-friendly Mn-based mineralization. Significantly, the durable nanozyme shells not only can enhance the cellular tolerance against severe physical stressors including dehydration and lytic enzyme, but also enable the survival of cells upon contact with high levels of toxic chemicals for prolonged periods. More importantly, these encased cells after shell removal via a facile biomolecule stimulus can fully resume growth and functions. This strategy is applicable to a broad range of living cells Hard cell: Individual living cells were encapsulated within biodegradable MnO2 nanozyme shells. These shells not only enhanced the cellular tolerance against severe physical stressors, but also enabled the survival of cells upon encountering high levels of toxic chemicals for prolonged times.
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Regioselective Intermolecular Allylic C−H Amination of Disubstituted Olefins via Rhodium/π-Allyl Intermediates ()
A method for catalytic intermolecular allylic C−H amination of trans-disubstituted olefins is reported. The reaction is efficient for a range of common nitrogen nucleophiles bearing one electron-withdrawing group, and proceeds under mild reaction conditions. Good levels of regioselectivity are observed for a wide range of electronically diverse trans-β-alkyl styrene substrates. A method for catalytic intermolecular allylic C−H amination of trans-disubstituted olefins has been developed that is efficient for a range of common nitrogen nucleophiles bearing one electron-withdrawing group (EWG), and proceeds under mild reaction conditions. Good levels of regioselectivity are observed for a wide range of electronically diverse trans-β-alkyl styrene substrates.
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Olefins from Natural Gas by Oxychlorination ()
Ethylene and propylene are the key building blocks of the chemical industry, but current processes are unable to close the growing gap between demand and manufacture. Reported herein is an exceptional europium oxychloride (EuOCl) catalyst for the selective (≥95 %) production of light olefins from ethane and propane by oxychlorination chemistry, thus achieving yields of ethylene (90 %) and propylene (40 %) unparalleled by any existing olefin production technology. Moreover, EuOCl is able to process mixtures of methane, ethane, and propane to produce the olefins, thereby reducing separation costs of the alkanes in natural gas. Finally, the EuOCl catalyst was supported on suitable carriers and evaluated in extrudate form, and preserves performance for >150 h under realistic process conditions. Gas up: Ethylene and propylene can be generated from ethane and propane, respectively, or from methane/ethane/propane mixtures, over a europium oxychloride catalyst. The reaction proceeds by oxychlorination with yields surpassing those of any existing technologies for alkene production. Its performance is preserved in technical form, and testifies to the practical relevance of this technology for the manufacture of light olefins.
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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. A strongly correlated system: A previously unidentified type of magnetism based on the rotational motion of protons within methyl groups is shown to occur in hexamethylbenzene. At lower temperatures spin–spin interactions exist between methyl groups aligned in a previously unclassified type of antiferromagnetic configuration.
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One-Step Reforming of CO2 and CH4 into High-Value Liquid Chemicals and Fuels at Room Temperature by Plasma-Driven Catalysis ()
The conversion of CO2 with CH4 into liquid fuels and chemicals in a single-step catalytic process that bypasses the production of syngas remains a challenge. In this study, liquid fuels and chemicals (e.g., acetic acid, methanol, ethanol, and formaldehyde) were synthesized in a one-step process from CO2 and CH4 at room temperature (30 °C) and atmospheric pressure for the first time by using a novel plasma reactor with a water electrode. The total selectivity to oxygenates was approximately 50–60 %, with acetic acid being the major component at 40.2 % selectivity, the highest value reported for acetic acid thus far. Interestingly, the direct plasma synthesis of acetic acid from CH4 and CO2 is an ideal reaction with 100 % atom economy, but it is almost impossible by thermal catalysis owing to the significant thermodynamic barrier. The combination of plasma and catalyst in this process shows great potential for manipulating the distribution of liquid chemical products in a given process. Liquid fuels and chemicals (e.g. acetic acid, methanol, ethanol, and formaldehyde) were synthesized in a one-step process from CO2 and CH4 at room temperature (30 °C) and atmospheric pressure for the first time by using a novel plasma reactor with a water electrode. The total selectivity to oxygenates was approximately 50–60 %, with acetic acid as the major component.
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Black Pigment Gallstone Inspired Platinum-Chelated Bilirubin Nanoparticles for Combined Photoacoustic Imaging and Photothermal Therapy of Cancers ()
Bilirubin (BR), a bile pigment that exerts potent antioxidant and anti-inflammatory effects, is also a major constituent of black pigment gallstones found in bile ducts under certain pathological conditions. Inspired by the intrinsic metal-chelating power of BR found in gallstones, herein we report a cisplatin-chelated BR-based nanoparticle (cisPt@BRNP) for use as a new photonic nanomedicine for combined photoacoustic imaging and photothermal therapy of cancers. The cisPt@BRNPs were prepared by simply mixing cisplatin with BRNPs, yielding ca. 150-nm-size NPs. Upon near-IR laser irradiation at 808 nm, cisPt@BRNPs generated considerable heat and induced clear death of cancer cells in vitro. Following intravenous injection into human colon cancer-bearing mice, cisPt@BRNPs allowed effective tumor visualization by photoacoustic imaging and remarkable antitumor efficacy by photothermal therapy, suggesting their potential for use as a new photonic nanomedicine for cancer therapy. The gall of it: A new class of near infrared light-responsive photonic nanomaterial which is biodegradable and biocompatible is developed based on the inherent metal-chelating ability of bilirubin, a bile pigment found in gall stones. The resulting cisplatin-chelated bilirubin nanoparticles (cisPt@BRNPs) are promising for combined photoacoustic imaging (PAI) and photothermal therapy (PTT) of cancers.
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Catanionic Coacervate Droplets as a Surfactant-Based Membrane-Free Protocell Model ()
We report on the formation of surfactant-based complex catanionic coacervate droplets in mixtures of decanoic acid and cetylpyridinium chloride or cetyltrimethylammonium bromide. We show that coacervation occurs over a broad range of composition, pH, and ionic strength. The catanionic coacervates consist of elongated micelles, sequester a wide range of solutes including water-soluble organic dyes, polysaccharides, proteins, enzymes, and DNA, and can be structurally stabilized by sodium alginate or gelatin-based hydrogelation. These results suggest that catanionic coacervates could be exploited as a novel surfactant-based membrane-free protocell model. Catanionic coacervates as protocells: Proteins, enzymes, and DNA are spontaneously sequestered within catanionic surfactant coacervates, thereby affording a novel protocell model.
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Potential-Cycling Synthesis of Single Platinum Atoms for Efficient Hydrogen Evolution in Neutral Media ()
Single-atom catalysts (SACs) have exhibited high activities for the hydrogen evolution reaction (HER) electrocatalysis in acidic or alkaline media, when they are used with binders on cathodes. However, to date, no SACs have been reported for the HER electrocatalysis in neutral media. We demonstrate a potential-cycling method to synthesize a catalyst comprising single Pt atoms on CoP-based nanotube arrays supported by a Ni foam, termed PtSA-NT-NF. This binder-free catalyst is centimeter-scale and scalable. It is directly used as HER cathodes, whose performances at low and high current densities in phosphate buffer solutions (pH 7.2) are comparable to and better than, respectively, those of commercial Pt/C. The Pt mass activity of PtSA-NT-NF is 4 times of that of Pt/C, and its electrocatalytic stability is also better than that of Pt/C. This work provides a large-scale production strategy for binder-free Pt SAC electrodes for efficient HER in neutral media. Singles suitable for HER: Large-area single Pt atoms on CoP-based nanotube arrays supported by Ni foams were synthesized by potential cycling. These binder-free electrocatalysts are centimeter-scale and can be scaled up further. They exhibit unparalleled performance when catalyzing the hydrogen evolution reaction in neutral media.
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Rotational Spectroscopy Probes Water Flipping by Full Fluorination of Benzene ()
The topology of the interaction of water with benzene changes drastically upon full HF substitution on the aromatic ring: the weak O−H⋅⋅⋅π hydrogen bond is replaced by a O⋅⋅⋅π linkage, of about the same strength. Hexafluorobenzene–water appears to be the prototype system to investigate this kind of weak bond. The pulsed Fourier transform microwave technique has been used for the detection of the rotational spectra of the normal species and five isotopologues which unambiguously led to the identification of the geometry. Quantum mechanical calculations have been performed to interpret the experimental evidence. Flipping water: The prototype system for the lone-pair⋅⋅⋅π-hole interaction, hexafluorobenzene–water, has been investigated by rotational spectroscopy. Interesting chemical and dynamic features have been found: a) fluorine substitution flips the water bond with benzene, from O−H⋅⋅⋅π to O⋅⋅⋅π hole; b) water is almost freely rotating above the ring and the spectrum of the complex appears to be that of a symmetric top.
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Specific and Direct Amplified Detection of MicroRNA with MicroRNA:Argonaute-2 Cleavage (miRACle) Beacons ()
MicroRNA detection is a valuable method for determining cell identity. Molecular beacons are elegant sensors that can transform intracellular microRNA concentration into a fluorescence intensity. While target binding enhances beacon fluorescence, the degree of enhancement is insufficient for demanding applications. The addition of specialty nucleases can enable target recycling and signal amplification, but this process complicates the assay. We have developed and characterized a class of beacons that are susceptible to the endogenous nuclease Argonaute-2 (Ago2). After purification of the complex by co-immunoprecipitation, microRNA:Ago2 cleavage (miRACle) beacons undergo site- and sequence-specific cleavage, and show a 13-fold fluorescence enhancement over traditional beacons. The system can be adapted to any microRNA sequence, and can cleave nuclease-resistant, non-RNA bases, potentially allowing miRACle beacons to be designed for cells without interference from non-specific nucleases. Simple sensors simulate substrate: MicroRNA detection with molecular beacons can be used for in situ genetic profiling. Beacons that are susceptible to the endogenous nuclease Argonaute-2 (Ago2) have now been developed. After purification of the complex by co-immunoprecipitation, microRNA:Ago2 cleavage (miRACle) beacons undergo site- and sequence-specific cleavage, and show a 13-fold fluorescence enhancement over traditional beacons.
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Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery ()
Messenger RNA (mRNA) represents a promising class of nucleic acid drugs. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′-terminal polyadenosine nucleotides (poly A) and poly A binding proteins (PABPs) for optimal expression, we complexed synthetic mRNA containing a poly A tail with PABPs in a stoichiometric manner and stabilized the ribonucleoproteins (RNPs) with a family of polypeptides bearing different arrangements of cationic side groups. We found that the molecular structure of these polypeptides modulates the degree of PABP-mediated enhancement of mRNA expression. This strategy elicits an up to 20-fold increase in mRNA expression in vitro and an approximately fourfold increase in mice. These findings suggest a set of new design principles for gene delivery by the synergistic co-assembly of mRNA with helper proteins. Although numerous carriers have been developed for mRNA delivery, the inefficient mRNA expression inside cells remains a major challenge. Inspired by the dependence of mRNA on 3′-terminal polyadenosine nucleotides (poly A) and poly A binding proteins (PABPs) for optimal expression, synthetic mRNA containing a poly A tail was complexed with PABPs in a stoichiometric manner.
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Spin Changes Accompany Ultrafast Structural Interconversion in the Ground State of a Cobalt Nitrosyl Complex ()
Ultrafast, reversible intersystem crossing (ISC) is reported under ambient conditions for the electronic ground state of the pentacoordinate cobalt nitrosyl complexes, [CoX2(NO)(PMePh2)2] (X=Cl, Br), in solution. ISCs on such short timescales are more typically observed in electronically excited states reached by absorption of ultraviolet or visible light. Singlet and triplet electron spin states of the complex, corresponding to two different isomers, are populated at room temperature, and the two isomers exchange on a timescale of a few picoseconds. Ultrafast two-dimensional infrared spectroscopy observes the change in wavenumber of the NO ligand band accompanying the isomerization and associated ISC on the (spin) adiabatic ground potential energy surface. Comparison of the dynamics of the chloro- and bromo-complexes shows that inertial effects of the ligand motion have a greater effect than spin–orbit coupling on determining the forward and reverse isomerization and ISC rates. The ground state intersystem crossing of a cobalt nitrosyl complex is shown to occur on an ultrafast time scale. The electron spin changing dynamics can be observed with 2DIR spectroscopy by probing the nuclear vibrational frequencies associated with each electronic state. Comparison of the spin-state exchange rates in two halido-substituted complexes shows that inertial effects outweigh ligand spin–orbit coupling effects.
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Black Phosphorus Quantum Dots Used for Boosting Light Harvesting in Organic Photovoltaics ()
Although organic photovoltaic devices (OPVs) have been investigated for more than two decades, the power conversion efficiencies of OPVs are much lower than those of inorganic or perovskite solar cells. One effective approach to improve the efficiency of OPVs is to introduce additives to enhance light harvesting as well as charge transportation in the devices. Here, black phosphorus quantum dots (BPQDs) are introduced in OPVs as an additive. By adding 0.055 wt % BPQDs relative to the polymer donors in the OPVs, the device efficiencies can be dramatically improved for more than 10 %. The weight percentage is much lower than that of any other additive used in OPVs before, which is mainly due to the two-dimentional structure as well as the strong broadband light absorption and scattering of the BPQDs. This work paves a way for using two-dimentional quantum dots in OPVs as a cost-effective approach to enhance device efficiencies. Strong light absorption: The power conversion efficiencies of organic photovoltaics have been improved by introducing black phosphorus quantum dots (BPQDs; 0.055 wt % relative to the donor polymers) due to the boosted light harvesting of the devices. The effect is attributed to the strong light absorption as well as the two-dimensional structure of the BPQDs. A pronounced size effect of BPQDs on the performance enhancement is observed.
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Organocatalytic Intramolecular [4+2] Cycloaddition between In Situ Generated Vinylidene ortho-Quinone Methides and Benzofurans ()
Described herein is the enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides and benzofurans. According to this methodology, a series of oxygen-containing [5-6-5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio- and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium-labeling experiments and high-resolution mass spectroscopy demonstrated that a vinylidene ortho-quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2-ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram-scale synthesis were achieved for this transformation. Triple play: The enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by a thiourea-catalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides (VQMs) and benzofurans is reported. A series of oxygen-containing [5-6-5] tricyclic heterocycles having various functional groups were synthesized with excellent enantio- and diastereoselectivities.
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Extended Ladder-Type Benzo[k]tetraphene-Derived Oligomers ()
Well-defined, fused-ring aromatic oligomers represent promising candidates for the fundamental understanding and application of advanced carbon-rich materials, though bottom-up synthesis and structure–property correlation of these compounds remain challenging. In this work, an efficient synthetic route was employed to construct extended benzo[k]tetraphene-derived oligomers with up to 13 fused rings. The molecular and electronic structures of these compounds were clearly elucidated. Precise correlation of molecular sizes and crystallization dynamics was established, thus demonstrating the pivotal balance between intermolecular interaction and molecular mobility for optimized processing of highly ordered solids of these extended conjugated molecules. Aromatic “rungs” of the ladder: A highly efficient thermodynamic annulation enables the bottom-up syntheses of well-defined, fused-ring oligomers that imitate graphene nanostripes. Electronic structures and crystallization dynamics of these oligomers are highly dependent on the molecular size.
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Bioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint ()
Blockade of the immunoinhibitory PD-1/PD-L1 pathway using monoclonal antibodies has shown impressive results with durable clinical antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have now been approved for the treatment of a number of tumor types, whereas the development of small molecules targeting immune checkpoints lags far behind. We characterized two classes of macrocyclic-peptide inhibitors directed at the PD-1/PD-L1 pathway. We show that these macrocyclic compounds act by directly binding to PD-L1 and that they are capable of antagonizing PD-L1 signaling and, similarly to antibodies, can restore the function of T-cells. We also provide the crystal structures of two of these small-molecule inhibitors bound to PD-L1. The structures provide a rationale for the checkpoint inhibition by these small molecules, and a description of their small molecule/PD-L1 interfaces provides a blueprint for the design of small-molecule inhibitors of the PD-1/PD-L1 pathway. Circle of life: Macrocyclic peptide inhibitors can block the PD-1/PD-L1 pathway by directly binding to PD-L1 and, similarly to anti-PD-L1 antibodies, they can restore the function of T-cells. Structures of the macrocycle/PD-L1 interfaces provide a foundation for the design of small-molecule inhibitors with antitumor properties.
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A Biomimetic Escape Strategy for Cytoplasm Invasion by Synthetic Particles ()
The translocation of nanomaterials or complex delivery systems into the cytosol is a major challenge in nanobiotechnology. After receptor-mediated endocytosis, most nanomaterials are sequestered and undergo degradation, therapy inactivation, or exocytosis. Herein we explore a novel surface particle coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell-invasive mechanisms, namely, receptor-mediated endocytosis, endolysosomal escape, and cytosolic particle release preserving cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical, or catalytic functionalities, thus opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting new developments in the biotechnological, pharmaceutical, and biomedical industries. A clean getaway: An engineered nanocoating composed of carbon nanotubes enabled particles with nano/micrometer dimensions to break through lysosomal membranes and invade the intracellular realm (see picture). The coated materials resemble viruses in terms of their structure and reproduce the viral cell-invasive mechanisms of receptor-mediated endocytosis, endolysosomal escape, and cytosolic particle release with the preservation of cell viability.
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An Ultraflexible Silicon–Oxygen Battery Fiber with High Energy Density ()
To satisfy the rapid development of portable and wearable electronics, it is highly desired to make batteries with both high energy densities and flexibility. Although some progress has been made in recent decades, the available batteries share critical problems of poor energy storage capacity and low flexibility. Herein, we have developed a silicon–oxygen battery fiber with high energy density and ultra-high flexibility by designing a coaxial architecture with a lithiated silicon/carbon nanotube hybrid fiber as inner anode, a polymer gel as middle electrolyte and a bare carbon nanotube sheet as outer cathode. The fiber showed a high energy density of 512 Wh kg−1 and could effectively work after bending for 20 000 cycles. These battery fibers have been further woven into flexible textiles for a large-scale application. A silicon–oxygen battery fiber with high energy density and ultra-high flexibility has been created. The coaxial architecture of the fiber was obtained by using a lithiated silicon/carbon nanotube hybrid fiber as inner anode, a polymer gel as middle electrolyte and a carbon nanotube sheet as outer cathode.
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Electron-Transfer and Hydride-Transfer Pathways in the Stoltz–Grubbs Reducing System (KOtBu/Et3SiH) ()
Recent studies by Stoltz, Grubbs et al. have shown that triethylsilane and potassium tert-butoxide react to form a highly attractive and versatile system that shows (reversible) silylation of arenes and heteroarenes as well as reductive cleavage of C−O bonds in aryl ethers and C−S bonds in aryl thioethers. Their extensive mechanistic studies indicate a complex network of reactions with a number of possible intermediates and mechanisms, but their reactions likely feature silyl radicals undergoing addition reactions and SH2 reactions. This paper focuses on the same system, but through computational and experimental studies, reports complementary facets of its chemistry based on a) single-electron transfer (SET), and b) hydride delivery reactions to arenes. Transfers: Triethylsilane and potassium tert-butoxide react to form a highly attractive and versatile system. The work herein highlights the reductive transformations which lead to 1) C−N bond cleavage in N-benzyl- and N-allylindoles and 2) reduction of polycyclic arenes to their dihydro derivatives.
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H2S-Activable MOF Nanoparticle Photosensitizer for Effective Photodynamic Therapy against Cancer with Controllable Singlet-Oxygen Release ()
Photodynamic therapy (PDT) has emerged as an important minimally invasive tumor treatment technology. The search for an effective photosensitizer to realize selective cancer treatment has become one of the major foci in recent developments of PDT technology. Controllable singlet-oxygen release based on specific cancer-associated events, as another major layer of selectivity mode, has attracted great attention in recent years. Here, for the first time, we demonstrated that a novel mixed-metal metal–organic framework nanoparticle (MOF NP) photosensitizer can be activated by a hydrogen sulfide (H2S) signaling molecule in a specific tumor microenvironment for PDT against cancer with controllable singlet-oxygen release in living cells. The effective removal of tumors in vivo further confirmed the satisfactory treatment effect of the MOF NP photosensitizer. Selective cancer treatment: A mixed-metal metal–organic framework nanoparticle photosensitizer has been activated by a H2S-signaling molecule in a specific tumor microenvironment for photodynamic therapy of cancer using controllable singlet-oxygen release. The effective removal of tumors in vivo confirms the satisfactory treatment effect of the photosensitizer.
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Selective C−O Bond Cleavage of Sugars with Hydrosilanes Catalyzed by Piers’ Borane Generated In Situ ()
Described herein is the selective reduction of sugars with hydrosilanes catalyzed by using Piers’ borane [(C6F5)2BH] generated in situ. The hydrosilylative C−O bond cleavage of silyl-protected mono- and disaccharides in the presence of a (C6F5)2BH catalyst, generated in situ from (C6F5)2BOH, takes place with excellent chemo- and regioselectivities to provide a range of polyols. A study of the substituent effects of sugars on the catalytic activity and selectivity revealed that the steric environment around the anomeric carbon (C1) is crucial. Piers’ borane [(C6F5)2BH], generated in situ, is demonstrated to promote the hydrosilylative reduction of sugars, thereby providing a series of linear or cyclic polyols with high chemo- and regioselectivities under mild conditions. Studies of catalytic reactivity and regioselectivity with regard to the C−O bond cleavage with hydrosilanes suggest an importance of the steric environment around the anomeric carbon center of the sugar.
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Valence Interconversion of Octahedral Nickel(II/III/IV) Centers ()
Three oxidation states (+2, +3, +4) of an octahedral nickel center were stabilized in a newly prepared RhNiRh trinuclear complex, [Ni{Rh(apt)3}2]n+ (apt=3- aminopropanethiolate), in which the nickel center was bound by six thiolato donors sourced from two redox-inert fac-[RhIII(apt)3] octahedral units. The three oxidation states of the octahedral nickel center were fully characterized by single-crystal X-ray crystallography, as well as spectroscopic, electrochemical, and magnetic measurements; all three were interconvertible, and the conversion was accompanied by changes in color, magnetism, and Jahn–Teller distortion. Bridge over troubled water: A series of S-bridged RhNiRh trinuclear complexes capable of supporting an octahedral nickel center in three different oxidation states (+2, +3, +4) have been isolated. Oxidation state interconversion is accompanied by changes in color, magnetism, and geometric Jahn–Teller distortions, with retention of the trinuclear structure.
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Visualization of Stereoselective Supramolecular Polymers by Chirality-Controlled Energy Transfer ()
Chirality-driven self-sorting is envisaged to efficiently control functional properties in supramolecular materials. However, the challenge arises because of a lack of analytical methods to directly monitor the enantioselectivity of the resulting supramolecular assemblies. Presented herein are two fluorescent core-substituted naphthalene-diimide-based donor and acceptor molecules with minimal structural mismatch and they comprise strong self-recognizing chiral motifs to determine the self-sorting process. As a consequence, stereoselective supramolecular polymerization with an unprecedented chirality control over energy transfer has been achieved. This chirality-controlled energy transfer has been further exploited as an efficient probe to visualize microscopically the chirality driven self-sorting. To the core: Presented herein are two fluorescent core-substituted naphthalene-diimide-based donor and acceptor molecules with minimal structural mismatch, and they comprise self-recognizing chiral motifs to facilitate the self-sorting process. Visual discrimination of the stereoselective self-sorted and co-assembled supramolecular polymers is presented by using chirality-controlled energy transfer.
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Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions ()
Multiple active individual molecular ruthenium catalysts have been pinpointed within growing polynorbornene, thereby revealing information on the reaction dynamics and location that is unavailable through traditional ensemble experiments. This is the first single-turnover imaging of a molecular catalyst by fluorescence microscopy and allows detection of individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization (ROMP) catalyst under synthetically relevant conditions (e.g. unmodified industrial catalyst, ambient pressure, condensed phase, ca. 0.03 m monomer). These results further establish the key fundamentals of this imaging technique for characterizing the reactivity and location of active molecular catalysts even when they are the minor components. Singled out: Single-turnover detection has enabled the spatiotemporal resolution of individual reactions within growing polymers. The addition of a spectator fluorophore to the polymerization of norbornene enabled individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization catalyst to be observed as a bright-green point flash by fluorescence microscopy.
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One-Step Multigram-Scale Biomimetic Synthesis of Psiguadial B ()
A gram-scale synthesis of psiguadial B, a purported inhibitor of human hepatoma cell growth, has been achieved in one step by a biomimetic three-component coupling of caryophyllene, benzaldehyde, and diformylphloroglucinol. This cascade reaction is catalyzed by N,N′-dimethylethylenediamine, and proceeds at ambient temperature to generate four stereocenters, two rings, one C−O bond, and three C−C bonds. Combined computational and experimental investigations suggest the biosynthesis of the natural product is non-enzyme mediated, and is the result of a Michael addition between caryophyllene and a reactive ortho-quinone methide, followed by two sequential intramolecular cationic cyclization events. A one-step multigram-scale synthesis of psiguadial B has been achieved using a biomimetic three-component coupling, thus generating three C−C bonds, one C−O bond, two rings, and four stereocenters. Combined synthetic and computational experiments suggest the reaction proceeds by a Michael addition of caryophyllene to an in situ generated ortho-quinone methide, followed by two sequential cationic cyclization events.
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Three-Dimensional Hierarchical Architectures Derived from Surface-Mounted Metal–Organic Framework Membranes for Enhanced Electrocatalysis ()
Inspired by the rapid development of metal–organic-framework-derived materials in various applications, a facile synthetic strategy was developed for fabrication of 3D hierarchical nanoarchitectures. A surface-mounted metal–organic framework membrane was pyrolyzed at a range of temperatures to produce catalysts with excellent trifunctional electrocatalytic efficiencies for the oxygen reduction, hydrogen evolution, and oxygen evolution reactions. Burnt to a crisp: Surface-mounted metal–organic framework (MOF) membranes were pyrolyzed to produce electrocatalytic nanomaterials with 3D nanoarchitectures and abundant catalytic sites. Cobalt contained in the MOF thin-film has a dual function; it facilitates growth of nitrogen-doped carbon nanotubes and promotes oxygen reduction, hydrogen evolution, and oxygen evolution reactions.
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Integration of Bromine and Cyanogen Bromide Generators for the Continuous-Flow Synthesis of Cyclic Guanidines ()
A continuous-flow process for the in situ on-demand generation of cyanogen bromide (BrCN) from bromine and potassium cyanide that makes use of membrane-separation technology is described. In order to circumvent the handling, storage, and transportation of elemental bromine, a continuous bromine generator using bromate–bromide synproportionation can optionally be attached upstream. Monitoring and quantification of BrCN generation was enabled through the implementation of in-line FTIR technology. With the Br2 and BrCN generators connected in series, 0.2 mmol BrCN per minute was produced, which corresponds to a 0.8 m solution of BrCN in dichloromethane. The modular Br2/BrCN generator was employed for the synthesis of a diverse set of biologically relevant five- and six-membered cyclic amidines and guanidines. The set-up can either be operated in a fully integrated continuous format or, where reactive crystallization is beneficial, in semi-batch mode. Cyanogen bromide on tap: The highly toxic but synthetically powerful reagent cyanogen bromide (BrCN) was generated in a fully continuous fashion from benign precursors and directly used for the synthesis of medicinally relevant N-heterocycles.
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Mass Production and Pore Size Control of Holey Carbon Microcages ()
Architectural control of porous solids, such as porous carbon cages, has received considerable attention for versatile applications because of their ability to interact with liquids and gases not only at the surface, but throughout the bulk. Herein we report a scalable, facile spray-pyrolysis route to synthesize holey carbon microcages with mosquito-net-like shells. Using the surfaces of water droplets as the growth templates, styrene–butadiene rubber macromolecules are controllably cross-linked, and size-controllable holes on the carbon shells are generated. The as-formed carbon microcages encapsulating Si nanoparticles exhibit enhanced lithium-storage performances for lithium-ion batteries. The scalable, inexpensive synthesis of porous carbon microcages with controlled porosity and the demonstration of outstanding electrochemical properties are expected to extend their uses in energy storage, molecular sieves, catalysis, adsorbents, water/air filters, and biomedical engineering. Holey controllable: Holey carbon microcages with controllable pore sizes are easily synthesized by a scalable spray-pyrolysis technique. Beyond energy storage, these porous, hollow carbon microcages can be further constructed into micro-containers for holding other functional materials with promising applications. Their lithium-ion storage ability for use in lithium-ion batteries is demonstrated.
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Repairing Nanoparticle Surface Defects ()
Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We utilized atomically thin semiconductor nanoplatelets as a convenient platform for studying, both microscopically and spectroscopically, the development of defects during ligand exchange with the conductive ligands Na4SnS4 and (NH4)4Sn2S6. These defects can be repaired via mild chemical or thermal routes, through the addition of L-type ligands or wet annealing, respectively. This results in a higher-quality, conductive, colloidally stable nanomaterial that may be used as the active film in optoelectronic devices. Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, the exchange of insulating ligands with conductive metal chalcogenide complexes introduces structural defects that act as traps for charge carriers. CdSe nanoplatelets were used as a model system to show that it is possible to minimize the formation of defects, as well as trigger surface healing, by a judicious choice of mild treatments.
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Synergistic Effects between Atomically Dispersed Fe−N−C and C−S−C for the Oxygen Reduction Reaction in Acidic Media ()
Various advanced catalysts based on sulfur-doped Fe/N/C materials have recently been designed for the oxygen reduction reaction (ORR); however, the enhanced activity is still controversial and usually attributed to differences in the surface area, improved conductivity, or uncertain synergistic effects. Herein, a sulfur-doped Fe/N/C catalyst (denoted as Fe/SNC) was obtained by a template-sacrificing method. The incorporated sulfur gives a thiophene-like structure (C−S−C), reduces the electron localization around the Fe centers, improves the interaction with oxygenated species, and therefore facilitates the complete 4 e− ORR in acidic solution. Owing to these synergistic effects, the Fe/SNC catalyst exhibits much better ORR activity than the sulfur-free variant (Fe/NC) in 0.5 m H2SO4. A sulfur-doped Fe/N/C catalyst with much better activity in the oxygen reduction reaction (ORR) in 0.5 m H2SO4 solution than the sulfur-free variant was developed. The incorporated sulfur atoms reduce the electron localization around the iron centers, improve the interaction with oxygenated species, and therefore facilitate the complete 4 e− ORR in acidic solution.
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Silver-Catalyzed Stereoselective Aminosulfonylation of Alkynes ()
A silver-catalyzed intermolecular aminosulfonylation of terminal alkynes with sodium sulfinates and TMSN3 is reported. This three-component reaction proceeds through sequential hydroazidation of the terminal alkyne and addition of a sulfonyl radical to the resultant vinyl azide. The method enables the stereoselective synthesis of a wide range of β-sulfonyl enamines without electron-withdrawing groups on the nitrogen atom. These enamines are found to be suitable for a variety of further transformations. Controllable assembly: The first intermolecular aminosulfonylation of terminal alkynes with sodium sulfinates and TMSN3 is reported. This three-component coupling, which shows excellent functional group tolerance, proceeds through sequential hydroazidation of the terminal alkyne and addition of a sulfonyl radical to the resultant vinyl azide. This enables the stereoselective synthesis of a wide range of β-sulfonyl N-unprotected enamines.
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Efficient Aryl Migration from an Aryl Ether to a Carboxylic Acid Group To Form an Ester by Visible-Light Photoredox Catalysis ()
We have developed a highly efficient aryl migration from an aryl ether to a carboxylic acid group through retro-Smiles rearrangement by visible-light photoredox catalysis at ambient temperature. Transition metals and a stoichiometric oxidant and base are avoided in the transformation. Inspired by the high efficiency of this transformation and the fundamental importance of C−O bond cleavage, we developed a novel approach to the C−O cleavage of a biaryl ether to form two phenolic compounds, as demonstrated by a one-pot, two-step gram-scale reaction under mild conditions. The aryl migration exhibits broad scope and can be applied to the synthesis of pharmaceutical compounds, such as guacetisal. Primary mechanistic studies indicate that the catalytic cycle occurs by a reductive quenching pathway. A great migration: In a retro-Smiles rearrangement under visible-light photoredox catalysis at ambient temperature, one aryl group of a diaryl ether migrated to the carboxy group to form an ester (see scheme). The transformation requires no transition metals and no stoichiometric oxidant or base and could be followed by saponification in a one-pot, two-step process enabling overall C−O cleavage of the aryl ether.
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Catalytic Asymmetric Mannich Reaction with N-Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate ()
N,O-acetals (NOAcs) were developed as bench stable surrogates for N-carbamoyl, (Boc, Cbz and Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. The NOAcs can be directly utilized in the chiral primary amine catalyzed Mannich reactions of both acyclic and cyclic β-ketocarbonyls with high yields and excellent stereoselectivity. The current reaction offers a straightforward approach in the asymmetric synthesis of α- or β-amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner. On the bench: N,O-acetals (NOAcs) were developed as bench-stable surrogates for N-carbamoyl (Boc, Cbz, Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. This reaction offers a straightforward approach for the asymmetric synthesis of α- or β-amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner. EWG=electron-withdrawing group, PG=protecting group.
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Formation of Stable Tin Perovskites Co-crystallized with Three Halides for Carbon-Based Mesoscopic Lead-Free Perovskite Solar Cells ()
We synthesized and characterized methylammonium (MA) mixed tri-halide tin perovskites (MASnIBr2−xClx) for carbon-based mesoscopic solar cells free of lead and hole-transporting layers. Varied SnCl2/SnBr2 ratios yielded tin perovskites with three halides (I, Br, and Cl) co-crystallized inside the tin-perovskite. When the SnCl2 proportion was ≥50 % (x≥1), phase separation occurred to give MASnI3−yBry and MASnCl3−zBrz in the stoichiometric proportions of their precursors, confirmed by XRD. A device with MASnIBr1.8Cl0.2 (SnCl2=10 %) showed the best photovoltaic performance: JSC=14.0 mA cm−2, VOC=380 mV, FF=0.573, and PCE=3.1 %, and long-term stability. Electrochemical impedance spectra (EIS) show superior charge recombination and dielectric relaxation properties for the MASnIBr1.8Cl0.2 cell. Transient PL decays showed the intrinsic problem of tin-based perovskites with average lifetimes less than 100 ps. Tin in: Stable tin perovskites co-crystalized with three different halide elements (I, Br, and Cl) were produced by the reaction of methylammonium (MA) iodide with SnCl2/SnBr2 mixtures at ratios equal to or less than 25/75. The best device made of a carbon-based mesoscopic electrode and MASnIBr1.8Cl0.2 exhibited a PCE of 3.1 %.
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Reductive Coupling of Acrylates with Ketones and Ketimines by a Nickel-Catalyzed Transfer-Hydrogenative Strategy ()
Nickel-catalyzed coupling of benzyl acrylates with activated ketones and imines provides γ-butyrolactones and lactams, respectively. The benzyl alcohol byproduct released during the lactonization/lactamization event is relayed to the next cycle where it serves as the reductant for C−C bond formation. This strategy represents a conceptually unique approach to transfer-hydrogenative C−C bond formation, thus providing examples of reductive heterocyclizations where hydrogen embedded within an alcohol leaving group facilitates turnover. Catch and release: Nickel-catalyzed coupling of benzyl acrylates with activated ketones and imines provides a direct entry to γ-butyrolactones and lactams, respectively. The benzyl alcohol by-product released during the lactonization/lactamization event is relayed to the next cycle, where it then serves as the reductant for C−C bond formation.
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Benzodisilacyclobutadienes: 8π-Electron Systems with an Antiaromatic Silicon Ring ()
Benzodisilacyclobutadienes 2 a–c were isolated as blue to green crystalline solids from the reaction of stable disilyne 1 and 1,2-dibromobenzenes in the presence of potassium graphite. In the solid state, substantial bond alternation was observed within the benzene rings of 2 a–c. In hexane, 2 a–c showed remarkable bathochromic shifts of the ππ* (HOMOLUMO) absorption bands at 625–670 nm. NMR spectra and theoretical calculations indicated that the diamagnetic ring currents of the benzene rings of 2 a–c are considerably reduced by contributions from the antiaromatic 1,2-disilacyclobutadienes. In their entirety, the obtained results indicate that 2 a–c represent 8π-electron systems that contain an antiaromatic 1,2-disilacyclobutadiene. Slowing the flow: Benzodisilacyclobutadienes (see structure) were synthesized and isolated as blue and green crystalline solids. According to their solid-state structures, UV/Vis absorption and NMR spectra, and theoretical calculations, these benzodisilacyclobutadienes exist as 8π-electron systems that contain an antiaromatic 1,2-disilacyclobutadiene.
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Bioinspired Total Synthesis of (−)-Vescalin: A Nonahydroxytriphenoylated C-Glucosidic Ellagitannin ()
The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (−)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg–Feringa–Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (−)-vescalin. Catch a tan(nin): The total synthesis of a first member of the nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannins, (−)-vescalin, is described. The route is closely tailored to the commonly proposed sequence of events leading to its biogenesis. Its characteristic 2,3,5-(S,R)-NHTP unit was elaborated by a copper(II)-mediated Wynberg–Feringa–Yamada-type phenolic coupling using the achiral bicyclic diamine N,N′-dimethylbispidine.
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Correct Modeling of Cisplatin: a Paradigmatic Case ()
Quantum chemistry is a useful tool in modern approaches to drug and material design, but only when the adopted model reflects a correct physical picture. Paradigmatic is the case of cis-diaminodichloroplatinum(II), cis-[Pt(NH3)2Cl2], for which the correct simulation of the structural and vibrational properties measured experimentally still remains an open question. By using this molecule as a proof of concept, it is shown that state-of-the-art quantum chemical calculations and a simple model, capturing the basic physical flavors, a cis-[Pt(NH3)2Cl2] dimer, can provide the accuracy required for interpretative purposes. The present outcomes have fundamental implications for benchmark studies aiming at assessing the accuracy of a given computational protocol. Two are needed for a valid prediction: A dimer of cis-[Pt(NH3)2Cl2] as a quantum chemical model for cisplatin provides the first quantitative agreement with experiment for structural and vibrational properties. This result indicates that a reliable in silico drug design requires a model capturing the essential physical picture of the system and a proper theoretical protocol.
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Organocatalytic Enantioselective Protonation for Photoreduction of Activated Ketones and Ketimines Induced by Visible Light ()
The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation is reported. A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a non-covalent chiral organocatalyst is effective for these transformations. With the flexible use of a chiral Brønsted acid or base in H+ transfer interchange to control the elusive enantioselective protonation, a variety of chiral α-hydroxy ketones and α-amino ketones were obtained with high yields and enantioselectivities. Enantioselective protonation: The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation relies on a transition-metal-free cooperative catalysis platform that harnesses dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a noncovalent chiral organocatalyst. A variety of chiral α-hydroxy ketones and α-amino ketones was obtained with high yields and enantioselectivities.
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Synthesis of Acylborons by Ozonolysis of Alkenylboronates: Preparation of an Enantioenriched Amino Acid Acylboronate ()
A concise synthesis of acylborons was achieved by ozonolysis of alkenyl MIDA (N-methyliminodiacetic acid) boronates. This reaction exhibits excellent functional-group tolerance and is applicable to various acyl MIDA boronates and potassium acyltrifluroborates (KATs) which could not be synthesized by previous methods. In addition, α-amino acylborons, which would be essential for peptide ligations, were prepared for the first time. The acylboron of l-alanine was obtained in high enantiopurity and found to be configurationally stable. Oligopeptide synthesis between the α-amino KATs and amino acid in dilute aqueous media was studied. In the (o)zone: Highly functionalized acylborons are prepared by ozonolysis of alkenyl MIDA boronates. The first synthesis of α-amino acylborons, including the enantiopure alanine-type acylboron was achieved by using this method. The products are essential for protein–protein conjugation by potassium acyltrifluoroborate ligation. Oligopeptide synthesis using α-amino acylborons proceeded in dilute aqueous medium and the alanine-type acylboron is configurationally stable under ligation conditions.
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Enzymatic Cascade Catalysis for the Synthesis of Multiblock and Ultrahigh-Molecular-Weight Polymers with Oxygen Tolerance ()
Synthesis of well-defined multiblock and ultrahigh-molecular-weight (UHMW) polymers has been a perceived challenge for reversible-deactivation radical polymerization (RDRP). An even more formidable task is to synthesize these extreme polymers in the presence of oxygen. A novel methodology involving enzymatic cascade catalysis is developed for the unprecedented synthesis of multiblock polymers in open vessels with direct exposure to air and UHMW polymers in closed vessels without prior degassing. The success of this methodology relies on the extraordinary deoxygenation capability of pyranose oxidase (P2Ox) and the mild yet efficient radical generation by horseradish peroxidase (HRP). The facile and green synthesis of multiblock and UHMW polymers using biorenewable enzymes under environmentally benign and scalable conditions provides a new pathway for developing advanced polymer materials. Ultrahigh: Enzymatic cascade catalysis enables the synthesis of multiblock (up to 10 blocks) copolymers and ultrahigh-molecular-weight polymers (UHMW; up to 2.3×106 g mol−1). The reaction employs a P2Ox-HRP system and can be run in vessels open to air, thus highlighting the oxygen tolerance of the process. P2Ox=pyranose oxidase, HRP=horseradish peroxidase, ACAC=acetylacetone, RAFT=reversible addition-fragmentation chain transfer.
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Enantioselective Total Synthesis of (−)-Deoxoapodine ()
The first enantioselective total synthesis of (−)-deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction for the desymmetrization of an advanced intermediate that introduces the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core was accessed by electrophilic C19-amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (−)-deoxoapodine with complete stereochemical control. A molybdenum-catalyzed enantioselective ring-closing metathesis reaction for the desymmetrization of an advanced intermediate is one of the key steps of the total synthesis of (−)-deoxoapodine. After C21-oxygenation, the pentacyclic core was accessed through amide activation and transannular spirocyclization. A dehydrative C6-etherification introduced the F-ring and the fourth contiguous stereocenter.
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Gold(III) Alkyne Complexes: Bonding and Reaction Pathways ()
The synthesis and characterization of hitherto hypothetical AuIII π-alkyne complexes is reported. Bonding and stability depend strongly on the trans effect and steric factors. Bonding characteristics shed light on the reasons for the very different stabilities between the classical alkyne complexes of PtII and their drastically more reactive AuIII congeners. Lack of back-bonding facilitates alkyne slippage, which is energetically less costly for gold than for platinum and explains the propensity of gold to facilitate C−C bond formation. Cycloaddition followed by aryl migration and reductive deprotonation is presented as a new reaction sequence in gold chemistry. Good as gold: The synthesis of hitherto hypothetical gold(III) π-alkyne complexes highlights the differences between classical platinum alkyne complexes and their drastically more reactive AuIII congeners. Alkyne bonding in these complexes is subject to a strong trans influence, with ligands trans to a pyridine N atom being bound significantly more strongly than those trans to an anionic C donor.
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Diradicaloid or Zwitterionic Character: The Non-Tetrahedral Unsaturated Compound [Si4{N(SiMe3)Dipp}4] with a Butterfly-type Si4 Substructure ()
The reduction of the tribromoamidosilane {N(SiMe3)Dipp}SiBr3 (Dipp=2,6-iPr2C6H3) with potassium graphite or magnesium resulted in the formation of [Si4{N(SiMe3)Dipp}4] (1), a bicyclo[1.1.0]tetrasilatetraamide. The Si4 motif in 1 does not adopt a tetrahedral substructure and exhibits two three-coordinate and two four-coordinate silicon atoms. The electronic situation on the three-coordinate silicon atoms is rationalized with positive and negative polarization based on EPR analysis, magnetization measurements, and DFT calculations as well as 29Si CP MAS NMR and multinuclear NMR spectroscopy in solution. Reactivity studies with 1 and radical scavengers confirmed the partial charge separation. Compound 1 reacts with sulfur to give a novel type of silicon sulfur cage compound substituted with an amido ligand, [Si4S3{N(SiMe3)Dipp}4] (2). A change in structure: The unsaturated butterfly-shaped Si4 ring compound 1 ([Si4{N(SiMe3)Dipp}4]; Dipp=2,6-iPr2C6H3) was obtained by reduction of {N(SiMe3)Dipp}SiBr3. Compound 1 exhibits positively and negatively polarized three-coordinate Si atoms with flexible geometry, as determined by experimental and computational studies. Reactions of 1 with 5 or 8 equiv of sulfur afforded compound 2, a new amido-substituted Si4S3 cage compound.
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Transition-Metal-Free Ring-Opening Silylation of Indoles and Benzofurans with (Diphenyl-tert-butylsilyl)lithium ()
A practical method is presented for ring opening various indoles and benzofurans with concomitant stereoselective silylation using readily generated (diphenyl-tert-butylsilyl)lithium to afford ortho-β-silylvinylanilines or -phenols. Dearomatization of the heteroarene core proceeds in the absence of any transition-metal catalyst through addition of a silyl anion and a subsequent stereoselective β-elimination. DFT calculations provide insight into the mechanism. Functionalizing C−X bond cleavage of heteroarenes is rare and generally requires transition-metal catalysts. Open for business: Ring-opening silylation of various indoles and benzofurans using diphenyl-tert-butylsilyllithium affords ortho-β-silylvinyl anilines or phenols. Dearomatization of the heteroarene core proceeds in the absence of any transition-metal catalyst through addition of a silyl anion and a subsequent stereoselective β-elimination.
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Conversion of Methane into Methanol and Ethanol over Nickel Oxide on Ceria–Zirconia Catalysts in a Single Reactor ()
The conversion of methane into alcohols under moderate reaction conditions is a promising technology for converting stranded methane reserves into liquids that can be transported in pipelines and upgraded to value-added chemicals. We demonstrate that a catalyst consisting of small nickel oxide clusters supported on ceria–zirconia (NiO/CZ) can convert methane to methanol and ethanol in a single, steady-state process at 723 K using O2 as an abundantly available oxidant. The presence of steam is required to obtain alcohols rather than CO2 as the product of catalytic combustion. The unusual activity of this catalyst is attributed to the synergy between the small Lewis acidic NiO clusters and the redox-active CZ support, which also stabilizes the small NiO clusters. Controlled oxidation: Methanol and ethanol are produced continuously from methane and oxygen in a single reaction over a catalyst consisting of NiO clusters on ceria–zirconia. Oxygen is the abundantly available oxidant for this reaction and the presence of steam ensures the production of alcohols as opposed to products of the complete combustion of methane.
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Highly Fluorescent Pyridinium Betaines for Light Harvesting ()
We report the findings of our experimental and theoretical investigations into the properties of pyridinium enolates and their potential utility in light-harvesting applications, such as in luminescent solar concentrators (LSCs). We present the synthesis, structures, photophysical characterization, and wavefunction-based quantum-chemical studies of five cyclobetaines. The performance of an LSC device incorporating one of these cyclobetaines is shown to be comparable to state-of-the-art devices. Experiment and theory: Pyridinium enolates and their potential utility in light-harvesting applications, such as in luminescent solar concentrators, were studied experimentally and theoretically. The synthesis, structures, photophysical properties, and wavefunction-based quantum-chemical studies of five cyclobetaines are presented.
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From Precursor Powders to CsPbX3 Perovskite Nanowires: One-Pot Synthesis, Growth Mechanism, and Oriented Self-Assembly ()
The colloidal synthesis and assembly of semiconductor nanowires continues to attract a great deal of interest. Herein, we describe the single-step ligand-mediated synthesis of single-crystalline CsPbBr3 perovskite nanowires (NWs) directly from the precursor powders. Studies of the reaction process and the morphological evolution revealed that the initially formed CsPbBr3 nanocubes are transformed into NWs through an oriented-attachment mechanism. The optical properties of the NWs can be tuned across the entire visible range by varying the halide (Cl, Br, and I) composition through subsequent halide ion exchange. Single-particle studies showed that these NWs exhibit strongly polarized emission with a polarization anisotropy of 0.36. More importantly, the NWs can self-assemble in a quasi-oriented fashion at an air/liquid interface. This process should also be easily applicable to perovskite nanocrystals of different morphologies for their integration into nanoscale optoelectronic devices. Cubes, wires, and assemblies: Single-crystalline perovskite nanowires were prepared directly from precursor powders in a single-step ligand-assisted process by ultrasonication. The nanowires likely resulted from the oriented attachment of nanocubes. Quasi-oriented self-assemblies of the perovskite nanowires were fabricated at air/liquid interfaces.
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Regioselective para-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase ()
The utilization of CO2 as a carbon source for organic synthesis meets the urgent demand for more sustainability in the production of chemicals. Herein, we report on the enzyme-catalyzed para-carboxylation of catechols, employing 3,4-dihydroxybenzoic acid decarboxylases (AroY) that belong to the UbiD enzyme family. Crystal structures and accompanying solution data confirmed that AroY utilizes the recently discovered prenylated FMN (prFMN) cofactor, and requires oxidative maturation to form the catalytically competent prFMNiminium species. This study reports on the in vitro reconstitution and activation of a prFMN-dependent enzyme that is capable of directly carboxylating aromatic catechol substrates under ambient conditions. A reaction mechanism for the reversible decarboxylation involving an intermediate with a single covalent bond between a quinoid adduct and cofactor is proposed, which is distinct from the mechanism of prFMN-associated 1,3-dipolar cycloadditions in related enzymes. Biocatalytic CO2 fixation: 3,4-Dihydroxybenzoic acid decarboxylases are shown to catalyze the regioselective para-carboxylation of the aromatic core of catechols under ambient conditions. The enzymes depend on the recently discovered prenylated FMN cofactor for catalysis, which is proposed to proceed via a monocovalently bound quinoid–cofactor intermediate.
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