Featured
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Silicon-RosIndolizine fluorophores with shortwave infrared absorption and emission profiles enable in vivo fluorescence imaging
Accessing longer-wavelength emitting organic fluorophores is critical for diagnostic imaging. Here a series of silicon-RosIndolizine fluorophores with emission maxima at 1,300 nm, 1,550 nm and 1,700 nm were synthesized. The fluorophores generate high-resolution in vivo fluorescence images in mice and establish design principles for future shortwave-infrared fluorophore designs.
- William E. Meador
- , Eric Y. Lin
- & Jared H. Delcamp
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Article
| Open AccessDynamic three-dimensional structures of a metal–organic framework captured with femtosecond serial crystallography
Time-resolved femtosecond crystallography (TR-SFX) is a powerful technique to monitor structural transitions in protein crystals at the atomic level, but its use in non-protein synthetic materials remains limited. Now TR-SFX has been used to visualize the structural dynamics of metal–organic frameworks, showing the potential of this tool to study the dynamic motion of crystalline porous materials.
- Jaedong Kang
- , Yunbeom Lee
- & Hyotcherl Ihee
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Article |
Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides
Ribosomally synthesized and post-translationally modified peptides (RiPPs) can have vast structural diversity and biological functions enabled by disparate post-translational modifications (PTMs). However, unconventional PTMs derived from non-RiPP biosynthesis are rarely reported. Now a class of lipopeptides featuring a distinct fatty-acyl-modified N terminus and the responsible RiPP/fatty-acid hybrid biosynthetic machinery have been characterized.
- Hengqian Ren
- , Chunshuai Huang
- & Huimin Zhao
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Research Briefing |
Identifying phase-separating biomolecular condensates in cells
We developed a high-throughput, unbiased strategy for the identification of endogenous biomolecular condensates by merging cell volume compression, sucrose density gradient centrifugation and quantitative mass spectrometry. We demonstrated the performance of this strategy by identifying both global condensate proteins and those responding to specific biological processes on a proteome-wide scale.
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Article |
Enantioselective propargylic amination and related tandem sequences to α-tertiary ethynylamines and azacycles
Enantioenriched α-disubstituted α-ethynylamines are valuable synthons to chiral α-tertiary amines and azacycles, but their facile access remains challenging. Now, sterically confined pyridinebisoxazoline ligands have been developed to facilitate highly enantioselective Cu(I)-catalysed propargylic amination of both aliphatic and aryl ketone-derived propargylic carbonates to give α-tertiary ethynylamines. Related tandem sequences are reported to synthesize quaternary azacycles.
- Zheng Zhang
- , Ying Sun
- & Jian Zhou
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Article
| Open AccessCage escape governs photoredox reaction rates and quantum yields
The spontaneous recombination of photogenerated radicals surrounded by solvent molecules is an important energy-wasting elementary step in photoredox reactions. Now the decisive role that cage escape plays in these reactions is shown in three benchmark photocatalytic reactions, with quantitative correlations observed between photoredox product formation rates and cage escape quantum yields.
- Cui Wang
- , Han Li
- & Oliver S. Wenger
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Article |
High-throughput and proteome-wide discovery of endogenous biomolecular condensates
High-throughput proteome-wide methods for identifying endogenous proteins that phase separate or partition into condensates during certain physiological events are needed but remain a challenge. Now, a high-throughput, unbiased and quantitative strategy can identify endogenous biomolecular condensates and screen proteins involved in phase separation on a proteome-wide scale.
- Pengjie Li
- , Peng Chen
- & Yiwei Li
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Article
| Open AccessPorphyrin-fused graphene nanoribbons
The insertion of metal atoms and heteroaromatic units provides a way to tune the optical, electronic and magnetic properties of graphene nanoribbons. Now the synthesis of a porphyrin-fused graphene nanoribbon with a narrow bandgap and high charge mobility has been achieved, and this material used to fabricate field-effect and single-electron transistors.
- Qiang Chen
- , Alessandro Lodi
- & Harry L. Anderson
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Article
| Open AccessReconfiguring hydrogel assemblies using a photocontrolled metallopolymer adhesive for multiple customized functions
Although hydrogels with complex, heterogeneous and reconfigurable structures are promising materials for use in intelligent systems, fabricating such hydrogels is challenging. Now it has been shown that they can be fabricated by reversibly gluing different hydrogel units using a photocontrolled metallopolymer adhesive. This method can be used to design hydrogels with customized functions.
- Jiahui Liu
- , Yun-Shuai Huang
- & Si Wu
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Article
| Open AccessExploring the frontiers of condensed-phase chemistry with a general reactive machine learning potential
Atomistic simulations have a broad range of applications from drug design to materials discovery. Machine learning interatomic potentials (MLIPs) have become an efficient alternative to computationally expensive ab initio simulations. Now a general reactive MLIP (called ANI-1xnr) has been developed and validated against a broad range of condensed-phase reactive systems.
- Shuhao Zhang
- , Małgorzata Z. Makoś
- & Justin S. Smith
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In Your Element |
A blueprint for catalysis
Ciro Romano, Jack I. Mansell, and David J. Procter have explored the versatility and selectivity of samarium diiodide, and its use as a radical relay catalyst.
- Ciro Romano
- , Jack I. Mansell
- & David J. Procter
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Article
| Open AccessThe anti-aromatic dianion and aromatic tetraanion of [18]annulene
A previous investigation of the anti-aromatic dianion of [18]annulene concluded that it consists of a mixture of two isomers. Now it has been shown that this dianion exists as a single isomer, with a different geometry from neutral [18]annulene, and that it can be reduced further to an aromatic tetraanion.
- Wojciech Stawski
- , Yikun Zhu
- & Harry L. Anderson
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Review Article |
Nanopore DNA sequencing technologies and their applications towards single-molecule proteomics
Nanopore label-free sequencing of DNA and RNA at the single-molecule level offers rapid readout, high accuracy, low cost and portability. This Review surveys technologies underpinning commercial and academic nanopore sequencing, and examines how underlying biochemical advances can fuel future developments in nanopore-based protein sequencing.
- Adam Dorey
- & Stefan Howorka
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Article |
Tunable molecular editing of indoles with fluoroalkyl carbenes
The rapid generation of molecular complexity from a given molecular scaffold is crucial to drug discovery and development. Now the chemodivergent molecular editing of indoles using fluoroalkyl carbenes has been developed to modularly access four different types of fluorine-containing N-heterocyclic compound with high molecular complexity.
- Shaopeng Liu
- , Yong Yang
- & Xihe Bi
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Perspective |
The impact of UV light on synthetic photochemistry and photocatalysis
Although generally perceived as an old-fashioned and unselective tool to build molecules, the photochemistry community is now re-discovering the power of UV light and is using key mechanistic information to develop new catalytic processes driven by visible light. This Perspective discusses the progress and impact of UV light in organic synthesis.
- Giulio Goti
- , Kavyasree Manal
- & Luca Dell’Amico
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Article |
Visualization of CO2 electrolysis using optical coherence tomography
Electrolysers can upgrade CO2 into high-value chemicals, but there are few tools capable of tracking the reactions that occur within these devices during operation. Now an electrolysis optical coherence tomography platform has been developed to visualize the electrochemical conversion of CO2 to CO, plus the movement of components, within the device.
- Xin Lu
- , Chris Zhou
- & Curtis P. Berlinguette
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News & Views |
Molecularly defined electrodes host a concert of protons and electrons
Electrocatalytic transformations often involve the concerted transfer of electrons and protons at electrode interfaces; however, these processes are not well understood. Now, experiments on an electrode that features well-defined molecular sites deepen fundamental understanding of such transfers to pave the way for future catalysts.
- Siyuan L. Xie
- & Eva M. Nichols
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Article |
Genetically encoded bioorthogonal tryptophan decaging in living cells
Developing a generalizable method for blocking and rescuing tryptophan (Trp) interactions would enable the gain-of-function manipulation of various Trp-containing proteins but has so far been challenging. Now a genetically encoded N1-vinyl-caged Trp capable of rapid and bioorthogonal decaging enables site-specific activation of Trp on a protein of interest within living cells.
- Yuchao Zhu
- , Wenlong Ding
- & Peng R. Chen
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Article |
Photoinduced dual bond rotation of a nitrogen-containing system realized by chalcogen substitution
Although photoinduced concerted multiple-bond-rotation processes are known in photoactive biological systems, the synthesis of compounds exhibiting similar behaviour has proven challenging. Now a thioamide-based system featuring chalcogen substituents has been shown to exhibit photoinduced C–N/C–C rotation; the rotation mode can be switched depending on external stimuli such as temperature and light irradiation.
- Shotaro Nagami
- , Rintaro Kaguchi
- & Akira Katsuyama
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Article
| Open AccessTandem catalysis enables chlorine-containing waste as chlorination reagents
While chlorinated compounds are ubiquitous in chemical synthesis, they have a negative impact on human health and the environment. Now, a sustainable tandem catalytic process has been developed that uses chlorine-containing waste as chlorination reagents. This approach represents a promising way for the viable management of chlorinated compounds.
- Mingyang Liu
- , Xinbang Wu
- & Paul J. Dyson
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Research Briefing |
Carbon isotope exchange for pharmaceutical radiolabelling through metal-catalysed functional group metathesis
A method for carbon isotope exchange involving a metal-catalysed metathesis reaction of in situ formed acyl chlorides is demonstrated. The platform provides access to 13C- or 14C-enriched carboxylic acids, including natural products and pharmaceuticals, without the need for radioactive gases, using a single carboxylic acid carbon donor.
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Thorium(iv)–antimony complexes exhibiting single, double, and triple polar covalent metal–metal bonds
Actinide–metal multiple bonds are relatively rare, with isolable examples under normal experimental conditions typically restricted to complexes containing a polar covalent σ bond supplemented by up to two dative π bonds. Now complexes featuring polar covalent double and triple bonds between thorium and antimony have been synthesized.
- Jingzhen Du
- , Kevin Dollberg
- & Stephen T. Liddle
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Article |
Highly entangled polyradical nanographene with coexisting strong correlation and topological frustration
The design of open-shell nanographenes is commonly limited to systems featuring a single magnetic origin. Now a strategy that combines topological frustration and electron–electron interactions has been developed to generate a butterfly-shaped nanographene that hosts four highly entangled π-spins and exhibits both ferromagnetic and anti-ferromagnetic coupling.
- Shaotang Song
- , Andrés Pinar Solé
- & Jiong Lu
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Article |
Tunable valence tautomerism in lanthanide–organic alloys
Valence tautomerism in lanthanide-based materials is rare. Now a one-dimensional samarium–pyrazine polymer has been shown to exhibit a temperature-induced hysteretic Sm(III)-to-Sm(II) reversible switch. The transition temperature is modulated in a 150 K window by alloying with Yb(II), presenting a strategy for developing new materials with chemically tunable magnetic switchability.
- Maja A. Dunstan
- , Anna S. Manvell
- & Kasper S. Pedersen
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A metal-catalysed functional group metathesis approach to the carbon isotope labelling of carboxylic acids
The preparation of 14C-labelled compounds is a crucial step in pharmaceutical development but typically requires using toxic, radioactive gases. Now a broadly applicable functional group metathesis reaction has been developed that forms 14C-labelled carboxylic acids in one pot, without added gases, via dynamic exchange with an easily handled carboxylic acid 14C source.
- R. Garrison Kinney
- , José Zgheib
- & Bruce A. Arndtsen
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Article |
A catalytic process enables efficient and programmable access to precisely altered indole alkaloid scaffolds
New drug leads can be developed through modification of a natural product’s framework, but this is possible only if the compound is abundant and contains modifiable moieties. Now a strategy is introduced for accessing a scarce indole alkaloid and several expanded, contracted and distorted analogues, one of which shows anti-cancer activity.
- Youming Huang
- , Xinghan Li
- & Amir H. Hoveyda
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News & Views |
Clever cryptand cage coordinates contaminants
Replicating the ability of enzymes and transport proteins to effectively bind anions is a considerable challenge for supramolecular chemists. A neutral organic cage has now been developed that selectively binds sulfate anions in water.
- Rosemary J. Goodwin
- & Nicholas G. White
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Article |
Diazobutanone-assisted isobaric labelling of phospholipids and sulfated glycolipids enables multiplexed quantitative lipidomics using tandem mass spectrometry
Lipidomics aims to uncover lipid functions in biological systems and disease. Quantifying lipids is challenging due to highly diverse chemical structures. Here a diazobutanone-assisted isobaric labelling method is developed that relies on diazobutanone and isobaric mass tags to target phosphate- and sulfate-containing lipids, enabling multiplexed lipidomic quantification in complex mixtures.
- Ting-Jia Gu
- , Peng-Kai Liu
- & Lingjun Li
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Article
| Open AccessA divergent intermediate strategy yields biologically diverse pseudo-natural products
Design strategies that possess both biological relevance and structural diversity may lead to compound collections that are enriched in diverse bioactivities. Now a diverse pseudo-natural product design principle has been established to efficiently explore biologically relevant chemical space. Through dearomatization reactions, a compound collection enriched in both structural and biological diversity was rapidly generated.
- Sukdev Bag
- , Jie Liu
- & Herbert Waldmann
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News & Views |
Asymmetric construction of sulfur(VI)–fluorine cores
Molecules containing a chiral S(VI) moiety have found extensive applications in drug design and organic synthesis, despite a lack of diverse asymmetric methods for their creation. Now, a ligand-mediated process has enabled the production of enantioenriched S(VI)–F motifs, providing a foundation for further stereospecific elaborations.
- Patrick R. Melvin
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Research Briefing |
Site-selective episulfonium formation on protein surfaces
Covalent protein conjugation facilitates the study of biological processes and the synthesis of therapeutic biomacromolecules. A method that uses vinyl thianthrenium reagents for the site-selective formation of highly reactive episulfonium species on proteins is demonstrated. These in situ-formed intermediates react with diverse nucleophiles, providing access to protein conjugates in one step without purification.
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| Open AccessOperando film-electrochemical EPR spectroscopy tracks radical intermediates in surface-immobilized catalysts
Although surface-bound molecular catalysts offer well-defined active sites on heterogeneous supports, it is challenging to identify key radical intermediates in the reaction mechanism. Now, a characterization method has been developed that combines film electrochemistry and EPR spectroscopy to track radical intermediates in real time, exemplified by alcohol oxidation with a surface-immobilized nitroxide.
- Maryam Seif-Eddine
- , Samuel J. Cobb
- & Maxie M. Roessler
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Mapping the mechanisms of oxidative addition in cross-coupling reactions catalysed by phosphine-ligated Ni(0)
The mechanism for the oxidative addition of aryl halides to nickel(0)–phosphine complexes was proposed over four decades ago. Now, this elementary reaction, which occurs during common cross-coupling reactions, has been re-examined. Both one- and two-electron pathways occur, and their relative contribution depends on the electronic properties of the reaction partners.
- Christina N. Pierson
- & John F. Hartwig
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Enantioselective sulfur(VI) fluoride exchange reaction of iminosulfur oxydifluorides
Chirality is an intrinsic property in unsymmetric three-dimensional molecular assembly, contributing to the utility of the corresponding process and the resulting scaffolds. Now, on the sulfur(VI) hub, a three-step sequential ligand-exchange method has been established with precise stereocontrol, enabling the enantioselective synthesis of optically active S(VI) functional molecules.
- Zhiyuan Peng
- , Shoujun Sun
- & Bing Gao
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Article |
Biocatalytic strategy for the construction of sp3-rich polycyclic compounds from directed evolution and computational modelling
The use of biocatalysis to support early-stage drug discovery campaigns remains largely untapped. Here, engineered biocatalysts enable the synthesis of sp3-rich polycyclic compounds through an intramolecular cyclopropanation of benzothiophenes, affording a class of complex scaffolds potentially useful for fragment-based drug discovery campaigns.
- David A. Vargas
- , Xinkun Ren
- & Rudi Fasan
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A charge-neutral organic cage selectively binds strongly hydrated sulfate anions in water
Very few charge-neutral synthetic anion receptors can function in water, and those known typically select weakly hydrated anions such as iodide. Now a neutral molecular cage capable of donating 12 hydrogen bonds has been synthesized and found to bind highly hydrated sulfate in water with a strong selectivity over weakly hydrated anions.
- Liuyang Jing
- , Evelyne Deplazes
- & Xin Wu
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Research Briefing |
A protein-templated selection approach for the identification of full ligands from DNA-encoded libraries
A protein-templated selection approach has been developed for the discovery of full ligands from dual-pharmacophore DNA-encoded libraries by incorporating fragment linking into the selection process. The performance of this method was demonstrated with selections against protein–protein interaction and protein–DNA interaction targets, through which potent and selective inhibitors were identified.
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| Open AccessBistability between π-diradical open-shell and closed-shell states in indeno[1,2-a]fluorene
Switching the magnetic state of a polycyclic conjugated hydrocarbon in a reversible and controlled manner is challenging. Now, by means of single-molecule scanning probe microscopy, an indenofluorene isomer on ultrathin NaCl films has been shown to adopt both open- and closed-shell states. Furthermore, bidirectional switching between the two states is achieved by changing the adsorption site of the molecule.
- Shantanu Mishra
- , Manuel Vilas-Varela
- & Leo Gross
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Article
| Open AccessChelation enables selectivity control in enantioconvergent Suzuki–Miyaura cross-couplings on acyclic allylic systems
Achieving selectivity control in allylic arylations is a long-standing challenge in catalysis. Now a rhodium-catalysed system demonstrates chemo-, regio- and enantioselectivity, enabling Suzuki–Miyaura-type arylation with racemic, non-symmetrical, acyclic allylic systems; chelation is speculated to facilitate oxidative addition and enable both enantiomers of the starting material to converge onto a single product.
- Violeta Stojalnikova
- , Stephen J. Webster
- & Stephen P. Fletcher
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Article |
Oxidative two-state photoreactivity of a manganese(IV) complex using near-infrared light
The design of highly oxidizing Earth-abundant transition metal complexes for photochemical applications is desirable, but progress in this area remains limited. Now a manganese(IV) diguanidylpyridine complex has been shown to photooxidize naphthalene, benzene and acetonitrile to their radical cations after excitation with near-infrared light. Experimental and theoretical studies indicate the presence of two distinct ligand-to-metal charge transfer excited states.
- Nathan R. East
- , Robert Naumann
- & Katja Heinze
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Article |
Protein-templated ligand discovery via the selection of DNA-encoded dynamic libraries
Dual-pharmacophore DNA-encoded chemical libraries enable the identification of two synergistic binders for a biological target, but subsequent linking of this pair is required to obtain a full ligand, which can be challenging. Here we report a protein-templated selection of DNA-encoded dynamic library that can identify full ligands from fragment libraries without the need for subsequent fragment linking.
- Yu Zhou
- , Wenyin Shen
- & Xiaoyu Li
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In Your Element |
Redefining peptide therapeutics with semaglutide
Thomas Kruse and Søren Østergaard reflect on the development of the GLP-1 analogue, semaglutide, which is reshaping peptide therapeutics in type 2 diabetes, weight management, and beyond.
- Thomas Kruse
- & Søren Østergaard
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Article
| Open AccessSmall-pore hydridic frameworks store densely packed hydrogen
Although hydrogen gas could serve as a promising future fuel, its high-capacity storage is a challenge. Now, a nanoporous magnesium borohydride framework is shown to store hydrogen as densely packed penta-dihydrogen clusters having well-defined orientations and directional interactions with the framework.
- Hyunchul Oh
- , Nikolay Tumanov
- & Yaroslav Filinchuk
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Article |
Near-atomic-resolution structure of J-aggregated helical light-harvesting nanotubes
Chromophore supramolecular assemblies have long been studied for their exotic photophysical properties arising from their local geometry and long-range sensitive excitonic couplings. Now a high-resolution structure of a model nanotubular system has revealed a uniform brick-layer molecular arrangement and a non-biological supramolecular motif—interlocking sulfonates—enabling clear understanding of supramolecular structure–excitonic property relationships.
- Arundhati P. Deshmukh
- , Weili Zheng
- & Justin R. Caram
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Article |
Determinants that enable disordered protein assembly into discrete condensed phases
Cells spatially organize biochemical reactions within membrane-bound and membraneless compartments. The extent to which intrinsically disordered proteins themselves can form discrete compartments or condensed phases is poorly understood. Now a pair of model IDRs that display orthogonality in condensation and the chain features governing selective assembly have been identified.
- Rachel M. Welles
- , Kandarp A. Sojitra
- & Matthew C. Good
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Article
| Open AccessUltrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
Light-induced ultrafast switching between the molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Two competing pathways have now been identified by which electronically excited quadricyclane molecules relax to the electronic ground state, facilitating interconversion between the two isomers on different timescales.
- Kurtis D. Borne
- , Joseph C. Cooper
- & Daniel Rolles
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Research Briefing |
Photodriven nitrogen fixation by lithium hydride
Dinitrogen (N2) fixation to ammonia (NH3) is typically challenging under mild conditions. Now, lithium hydride (LiH) is shown to mediate photodriven N2 fixation under ambient conditions. Under ultraviolet illumination, LiH is photolysed to release H2, leaving electrons residing in surface hydrogen vacancies, which facilitate N2 activation and photocatalytic NH3 synthesis.
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Article
| Open AccessThe synthesis and characterization of an iron(VII) nitrido complex
Complexes of iron in high oxidation states play a pivotal role as active intermediates in numerous catalytic processes. Now, using a multimethod approach on a single molecular system, it has been shown that a stable high-valent Fe(VI) nitride can be converted to a reactive, superoxidized, heptavalent Fe(VII) nitride.
- Martin Keilwerth
- , Weiqing Mao
- & Karsten Meyer
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Article |
Synthesis of polysubstituted azepanes by dearomative ring expansion of nitroarenes
While saturated N-heterocycles are widespread motifs in drug discovery, the seven-membered ring azepane is highly underrepresented. Now nitroarenes have been validated as competent substrates for azepane synthesis through conversion into singlet nitrenes for ring enlargement via N insertion and hydrogenolysis. This enables a highly versatile access towards polysubstituted azepanes in just two steps.
- Rory Mykura
- , Raquel Sánchez-Bento
- & Daniele Leonori