Synthesis of Gold(I)−Trifluoromethyl Complexes and their Role in Generating Spectroscopic Evidence for a Gold(I)−Difluorocarbene Species

Synthesis of Gold(I)−Trifluoromethyl Complexes and their Role in Generating Spectroscopic Evidence for a Gold(I)−Difluorocarbene Species

A new method to access [Au(CF3)(NHC)] complexes has been developed, leading to the discovery of a new trimethylsilyl incorporated gold−NHC trifluoromethyl complex. This, in turn, led to the development of a new and straightforward strategy for the “one fluoride” abstraction affording, for the first time, spectroscopic evidence of the corresponding gold(I)−NHC difluorocarbene analogue.

Abstract

Readily prepared and bench‐stable [Au(CF3)(NHC)] compounds were synthesized by using new methods, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF2 precursors (NHC=N‐heterocyclic carbene). The mechanism of formation of these species was investigated. Consequently, a new and straightforward strategy for the mild and selective cleavage of a single carbon/fluorine bond from [Au(CF3)(NHC)] complexes was attempted and found to be reversible in the presence of an additional nucleophilic fluoride source. This straightforward technique has led to the unprecedented spectroscopic observation of a gold(I)−NHC difluorocarbene species.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Sofie M. P. Vanden Broeck, David J. Nelson, Alba Collado, Laura Falivene, Luigi Cavallo, David B. Cordes, Alexandra M. Z. Slawin, Kristof Van Hecke, Fady Nahra, Catherine S. J. Cazin, Steven P. Nolan
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100195

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A Cyclometalated IrIII Complex Conjugated to a Coumarin Derivative Is a Potent Photodynamic Agent against Prostate Differentiated and Tumorigenic Cancer Stem Cells

A Cyclometalated IrIII Complex Conjugated to a Coumarin Derivative Is a Potent Photodynamic Agent against Prostate Differentiated and Tumorigenic Cancer Stem Cells

A cyclometalated IrIII complex conjugated to a far‐red‐emitting coumarin, IrIII‐COUPY, is a very promising photosensitizer suitable for photodynamic therapy of cancer. It efficiently eliminates both prostate bulk, differentiated and prostate, hardly treatable cancer stem cells simultaneously and with a similar efficacy. Thus, photo‐induced therapy with IrIII‐COUPY conjugates, such as photodynamic therapy, might provide a new approach for prostate cancer treatment.

Abstract

A cyclometalated IrIII complex conjugated to a far‐red‐emitting coumarin, IrIII‐COUPY (3), was recently shown as a very promising photosensitizer suitable for photodynamic therapy of cancer. Therefore, the primary goal of this work was to deepen knowledge on the mechanism of its photoactivated antitumor action so that this information could be used to propose a new class of compounds as drug candidates for curing very hardly treatable human tumors, such as androgen resistant prostatic tumors of metastatic origin. Conventional anticancer chemotherapies exhibit several disadvantages, such as limited efficiency to target cancer stem cells (CSCs), which are considered the main reason for chemotherapy resistance, relapse, and metastasis. Herein, we show, using DU145 tumor cells, taken as the model of hormone‐refractory and aggressive prostate cancer cells resistant to conventional antineoplastic drugs, that the photoactivated conjugate 3 very efficiently eliminates both prostate bulk (differentiated) and prostate hardly treatable CSCs simultaneously and with a similar efficiency. Notably, the very low toxicity of IrIII‐COUPY conjugate in the prostate DU145 cells in the dark and its pronounced selectivity for tumor cells compared with noncancerous cells could result in low side effects and reduced damage of healthy cells during the photoactivated therapy by this agent. Moreover, the experiments performed with the 3D spheroids formed from DU145 CSCs showed that conjugate 3 can penetrate the inner layers of tumor spheres, which might markedly increase its therapeutic effect. Also interestingly, this conjugate induces apoptotic cell death in prostate cancer DU145 cells associated with calcium signaling flux in these cells and autophagy. To the best of our knowledge, this is the first study demonstrating that a photoactivatable metal‐based compound is an efficient agent capable of killing even hardly treatable CSCs.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Vojtech Novohradsky, Lenka Markova, Hana Kostrhunova, Jana Kasparkova, José Ruiz, Vicente Marchán, Viktor Brabec
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100568

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1,2‐Carbopentafluorophenylation of Alkynes: The Metallomimetic Pull‐Push Reactivity of Tris(pentafluorophenyl)borane

1,2‐Carbopentafluorophenylation of Alkynes: The Metallomimetic Pull‐Push Reactivity of Tris(pentafluorophenyl)borane

The novel three‐component coupling of an allylsilane, an arylacetylene, and a C6F5 group from tris(pentafluorophenyl)borane [B(C6F5)3] is enabled by the pull‐push reactivity of B(C6F5)3. Tetrafluoronaphthalenes can be prepared from the resultant C6F5‐substituted 1,3‐dienes by a photochemical 6π‐electrocyclization. The reaction using a 2‐substituted furan or a silyl enolate instead of an allylsilane also affords a novel three‐component coupling product.

Abstract

We report the novel single‐step 1,2‐dicarbofunctionalization of an arylacetylene with an allylsilane and tris(pentafluorophenyl)borane [B(C6F5)3] involving C−C bond formation with C−H bond scission at the β‐position to the silicon atom of an allylsilane and B→C migration of a C6F5 group. The 1,2‐carbopentafluorophenylation occurs smoothly without the requirement for a catalyst or heating. Mechanistic studies suggest that the metallomimetic “pull‐push” reactivity of B(C6F5)3 imparts consecutive electrophilic and nucleophilic characteristics to the benzylic carbon of the arylacetylene. Subsequent photochemical 6π‐electrocyclization affords tetrafluoronaphthalenes, which are important in the pharmaceutical and materials sciences. Owing to the unique reactivity of B(C6F5)3, the 1,2‐carbopentafluorophenylation using 2‐substituted furan proceeded with ring opening, and the reaction using silyl enolates formed a C−C bond with C−O bond scission at the silyloxy‐substituted carbon.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Masatoshi Shibuya, Miki Matsuda, Yoshihiko Yamamoto
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202101090

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A Stable Homoleptic Divinyl Tetrelene Series

A Stable Homoleptic Divinyl Tetrelene Series

Silylene? NHO Problem! Access to a new lithiated anionic N‐heterocyclic olefin (NHO) yields a complete acyclic divinyltetrelene series.

Abstract

The synthesis of the new bulky vinyllithium reagent (MeIPr=CH)Li, (MeIPr=[(MeCNDipp)2C]; Dipp=2,6‐iPr2C6H3) is reported. This vinyllithium precursor was found to act as a general source of the anionic 2σ, 2π‐electron donor ligand [MeIPr=CH]. Furthermore, a high‐yielding route to the degradation‐resistant SiII precursor MeIPr⋅SiBr2 is presented. The efficacy of (MeIPr=CH)Li in synthesis was demonstrated by the generation of a complete inorganic divinyltetrelene series (MeIPrCH)2E: (E=Si to Pb). (MeIPrCH)2Si: represents the first two‐coordinate acyclic silylene not bound by heteroatom donors, with dual electrophilic and nucleophilic character at the SiII center noted. Cyclic voltammetry shows this electron‐rich silylene to be a potent reducing agent, rivalling the reducing power of the 19‐electron complex cobaltocene (Cp2Co).

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Matthew M. D. Roy, Samuel R. Baird, Eike Dornsiepen, Lucas A. Paul, Linkun Miao, Michael J. Ferguson, Yuqiao Zhou, Inke Siewert, Eric Rivard
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100969

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Supramolecular Coordination Cages Based on N‐Heterocyclic Carbene‐Gold(I) Ligands and Their Precursors: Self‐Assembly, Structural Transformation and Guest‐Binding Properties

Supramolecular Coordination Cages Based on N‐Heterocyclic Carbene‐Gold(I) Ligands and Their Precursors: Self‐Assembly, Structural Transformation and Guest‐Binding Properties

Systematic design and self‐assembly of complex supramolecular coordination cages with predictable configurations has been a long‐standing challenge in chemistry, which is as mysterious as the starry sky depicted in the cover image. This work reports a trackable CpZr‐involved cage to cage conversion to generate a heteroleptic V2E3 cage from two homoleptic cages with different geometries of V2E3 and V4E6. Moreover, SCC‐2 cage possesses a cationic cavity allowing the encapsulation of a series of sulfonate anionic guests. More information can be found in the Full Paper by S. Bai, Y.‐F. Han, et al. (DOI: 10.1002/chem.202100710).

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Wen‐Jie Shi, Dan Liu, Xin Li, Sha Bai, Yao‐Yu Wang, Ying‐Feng Han
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202101551

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Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

Plant‐Derived Stilbenoids as DNA‐Binding Agents: From Monomers to Dimers

The stilbenoid (±)‐trans‐δ‐viniferin, deriving from trans‐resveratrol dimerization, binds to minor and major grooves of B‐DNA, and to 3’‐ and 5’‐ends of G‐quadruplex DNA by stacking on the outer quartets accompanied by rearrangement of flanking residues. Consistent with the ability to tightly interact with different DNA secondary structures, (±)‐trans‐δ‐viniferin shows DNA damaging activity.

Abstract

Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)‐trans‐δ‐viniferin, deriving from trans‐resveratrol dimerization, was investigated in its ability to target DNA duplex and G‐quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)‐trans‐δ‐Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3’‐ and 5’‐ends of a G‐quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)‐trans‐δ‐viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)‐trans‐δ‐viniferin and trans‐resveratrol, i. e. (±)‐pterostilbene‐trans‐dihydrodimer and trans‐pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at μM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G‐quadruplex structures.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Chiara Platella, Stefania Mazzini, Ettore Napolitano, Luce M. Mattio, Giovanni Luca Beretta, Nadia Zaffaroni, Andrea Pinto, Daniela Montesarchio, Sabrina Dallavalle
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202101229

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Sustainable and Robust Graphene Cellulose Paper Decorated with Lithiophilic Au Nanoparticles to Enable Dendrite‐free and High‐Power Lithium Metal Anode

Sustainable and Robust Graphene Cellulose Paper Decorated with Lithiophilic Au Nanoparticles to Enable Dendrite‐free and High‐Power Lithium Metal Anode

Sustainable graphene cellulose paper decorated with lithiophilic Au nanoparticles provides abundant nucleation sites and guarantees uniform Li deposition. And the large specific surface area of cellulose paper lowers local current density and avoids concentration polarization near the surface of electrode. Meanwhile, cellulose paper scaffold with good mechanical strength substantially alleviates the volume expansion of metal Li. Benefited from the synergy between Au nanoparticles and cellulose paper, the electrochemical performance of the Au−GCP electrode is significantly improved even at high current density.

Abstract

Lithium metal anodes (LMAs) with high energy density have recently captured increasing attention for development of next‐generation batteries. However, practical viability of LMAs is hindered by the uncontrolled Li dendrite growth and infinite dimension change. Even though constructing 3D conductive skeleton has been regarded as a reliable strategy to prepare stable and low volume stress LMAs, engineering the renewable and lithiophilic conductive scaffold is still a challenge. Herein, a robust conductive scaffold derived from renewable cellulose paper, which is coated with reduced graphene oxide and decorated with lithiophilic Au nanoparticles, is engineered for LMAs. The graphene cellulose fibres with high surface area can reduce the local current density, while the well‐dispersed Au nanoparticles can serve as lithiophilic nanoseeds to lower the nucleation overpotential of Li plating. The coupled relationship can guarantee uniform Li nucleation and unique spherical Li growth into 3D carbon matrix. Moreover, the natural cellulose paper possesses outstanding mechanical strength to tolerate the volume stress. In virtue of the modulated deposition behaviour and near‐zero volume change, the hybrid LMAs can achieve reversible Li plating/stripping even at an ultrahigh current density of 10 mA cm−2 as evidenced by high Coulombic efficiency (97.2 % after 60 cycles) and ultralong lifespan (1000 cycles) together with ultralow overpotential (25 mV). Therefore, this strategy sheds light on a scalable approach to multiscale design versatile Li host, promising highly stable Li metal batteries to be feasible and practical.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Wan‐Yue Diao, Dan Xie, Yan‐Fei Li, Ru Jiang, Fang‐Yu Tao, Hai‐Zhu Sun, Xing‐Long Wu, Xiao‐Ying Zhang, Jing‐Ping Zhang
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100440

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Self‐Assembly and Aggregation‐Induced Emission in Aqueous Media of Responsive Luminescent Copper(I) Coordination Polymer Nanoparticles

Self‐Assembly and Aggregation‐Induced Emission in Aqueous Media of Responsive Luminescent Copper(I) Coordination Polymer Nanoparticles

Stable copper(I) coordination polymer nanoparticles (CPNs) are self‐assembled in water and they display solvent composition‐responsive behavior that can be followed by emission of the aggregates. The dramatic differences in the emission energy and the morphology of the aggregates have been attributed to changes in the coordination sphere around the copper centers.

Abstract

Luminescent copper(I)‐based compounds have recently attracted much attention since they can reach very high emission quantum yields. Interestingly, Cu(I) clusters can also be emissive, and the extension from small molecules to larger architecture could represent the first step towards novel materials that could be obtained by programming the units to undergo self‐assembly. However, for Cu(I) compounds the formation of supramolecular systems is challenging due to the coordinative diversity of copper centers. This works shows that this diversity can be exploited in the construction of responsive systems. In detail, the changes in the emissive profile of different aggregates formed in water by phosphine‐thioether copper(I) derivatives were followed. Our results demonstrate that the self‐assembly and disassembly of Cu(I)‐based coordination polymeric nanoparticles (CPNs) is sensitive to solvent composition. The solvent‐induced changes are related to modifications in the coordination sphere of copper at the molecular level, which alters not only the emission profile but also the morphology of the aggregates. Our findings are expected to inspire the construction of smart supramolecular systems based on dynamic coordinative metal centers.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Hugo Hernández‐Toledo, Hugo Torrens, Marcos Flores‐Álamo, Luisa De Cola, Guillermo Moreno‐Alcántar
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100865

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Synthesis of Tetrahedranes Containing the Unique Bridging Hetero‐Dipnictogen Ligand EE′ (E ≠ E′=P, As, Sb, Bi)

Synthesis of Tetrahedranes Containing the Unique Bridging Hetero‐Dipnictogen Ligand EE′ (E ≠ E′=P, As, Sb, Bi)

New synthetic pathway towards organometallic tetrahedrane derivatives [{CpMo(CO)2}2(μ,η22EE′)] (E≠E′=P, As, Sb, Bi) involving a hetero‐dipnictogen ligand is reported, leading to dramatic yield enhancements for already known compounds, the reduction of reaction steps and access to so far unknown AsSb, AsBi and SbBi ligand complexes, which feature unseen covalent bonds between two different heavy group 15 elements without organic substituents.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Luis Dütsch, Christoph Riesinger, Gábor Balázs, Manfred Scheer
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100663

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Unveiling the Hidden σ‐Dimerization of a Kinetically Protected Olympicenyl Radical

Unveiling the Hidden σ‐Dimerization of a Kinetically Protected Olympicenyl Radical

The hitherto undetected σ‐dimerization pathway in an olympicenyl system was revealed from both theoretical and experimental perspectives. Theoretical calculations gave clear structural and energetic profiles for the σ‐dimerization, and regioselective oxidation of the olympicenyl radical afforded biolympicenylidene with significant singlet diradical character and high resistance towards both thermal and photochemical ring‐cyclization.

Abstract

The σ‐dimer of a kinetically protected olympicenyl radical, which evaded the experimental detection, was revealed by conversion into biolympicenylidene with E‐configuration in a regioselective manner. The complicated stereochemistry and energetics of the σ‐dimers derived from C2v symmetry and uneven spin distribution of the olympicenyl radical were revealed by the theoretical calculations, and the energetic preference of π‐dimer over σ‐dimer by a minute gap was disclosed. The E‐biolympicenylidene, a polycyclic ene structure previously considered as reactive intermediate in the phenalenyl radical system, exhibited exceptional stability, which allowed for a detailed investigation on its singlet diradical character and physical properties by means of X‐ray crystallography, UV‐vis‐NIR absorption/emission spectroscopy and cyclic voltammetry, and assisted by theoretical calculations. The E‐biolympicenylidene showed high resistance towards both thermal and photochemical ring‐cyclization reactions, which was attributed to high activation energies for the rate‐determining electrocyclization operated on both disrotatory and conrotatory mode, as well as a small spin density at the bonding sites for the radical‐radical coupling process.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Qin Xiang, Jun Xu, Jing Guo, Yanfeng Dang, Zhanqiang Xu, Zebing Zeng, Zhe Sun
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100631

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Supramolecular Alloys from Fluorinated Hybrid Tri4Di6 Imine Cages

Supramolecular Alloys from Fluorinated Hybrid Tri4Di6 Imine Cages

A supramolecular alloy, freely composed of eight hybrid Tri4Di6 imine cages with a tunable degree of fluorination can be created with high crystallinity. Although the fluorinated and the non‐fluorinated building blocks used herein differ vastly in reactivity, gaining control over the outcome of the self‐assembly process was achieved by carefully controlling the feed ratio.

Abstract

To create innovative materials, efficient control and engineering of pore sizes and their characteristics, crystallinity and stability is required. Eight hybrid Tri4Di6 imine cages with a tunable degree of fluorination and one fully fluorinated Tri4Di6 imine cage are investigated. Although the fluorinated and the non‐fluorinated building blocks used herein differ vastly in reactivity, it was possible to gain control over the outcome of the self‐assembly process, by carefully controlling the feed ratio. This represents the first hybrid material based on fluorinated/hydrogenated porous organic cages (POCs). These cages with unlimited miscibility in the solid state were obtained as highly crystalline samples after recrystallization and even showed retention of the crystal lattice, forming alloys. All mixtures and the fully fluorinated Tri4Di6 imine cage were analyzed by MALDI‐MS, single‐crystal XRD, powder XRD and in regard to thermal stability (TGA).

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Tom Kunde, Tobias Pausch, Bernd M. Schmidt
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100891

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Bis(Iminophosphorano)‐Substituted Pyridinium Ions and their Corresponding Bispyridinylidene Organic Electron Donors

Bis(Iminophosphorano)‐Substituted Pyridinium Ions and their Corresponding Bispyridinylidene Organic Electron Donors

Optimized synthetic routes to pyridinium ions featuring two strongly π‐donating R3P=N− substituents are presented. These substituents cause severe disruption in aromaticity in these cations, and also impart exceptional reducing ability to the related bispyridinylidenes (neutral 2 e‐ donors). Preliminary reactivity studies show some enhanced reducing capabilities owing to the low redox potential of the bispyridinylidene.

Abstract

Optimized synthetic procedures for pyridinium ions featuring iminophosphorano (−N=PR3; R=Ph, Cy) π‐donor substituents in the 2‐ and 4‐ positions are described. Crystallographic and theoretical studies reveal that the strongly donating substituents severely polarize the π‐electrons of the pyridyl ring at the expense of aromaticity. Moreover, the pyridinium ions are readily deprotonated to generate powerful bispyridinylidene (BPY) organic electron donors. Electrochemical studies show exceptionally low redox potentials for the two‐electron BPY/BPY2+ couples, ranging from −1.71 V vs the saturated calomel electrode for 3PhPh (with four Ph3P=N− groups) to −1.85 V for 3CyCy (with four Cy3P=N− groups). These new compounds represent the most reducing neutral organic electron donors (OEDs) currently known. Some preliminary reductions involving 3CyCy showed enhanced capability owing to its low redox potential, such as the thermally activated reduction of an aryl chloride, but purification challenges were often encountered.

Wiley: Chemistry – A European Journal: Table of Contents
Authors: Brandon L. Frenette, Nadine Arsenault, Sarah L. Walker, Andreas Decken, C. Adam Dyker
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100318

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Coupling Strategy for CO2 Valorization Integrated with Organic Synthesis by Heterogeneous Photocatalysis

Coupling Strategy for CO2 Valorization Integrated with Organic Synthesis by Heterogeneous Photocatalysis

The photoredox‐catalyzed win–win coupling strategy, in which CO2 valorization is integrated with organic synthesis in one reaction system, provides a promising approach that enables sufficient utilization of excited electrons and holes to achieve feasible and sustainable light‐mediated artificial photosynthesis.

Abstract

Photocatalytic reduction of CO2 to solar fuels and/or fine chemicals is a promising way to increase the energy supply and reduce greenhouse gas emissions. However, the conventional reaction system for CO2 photoreduction with pure H2O or sacrificial agents usually suffers from low catalytic efficiency, poor stability, or cost‐ineffective atom economy. A recent surge of developments, in which photocatalytic CO2 valorization is integrated with selective organic synthesis into one reaction system, indicates an efficient modus operandi that enables sufficient utilization of photogenerated electrons and holes to achieve the goals for sustainable economic and social development. In this Review we discuss current advances in cooperative photoredox reaction systems that integrate CO2 valorization with organics upgrading based on heterogeneous photocatalysis. The applications and virtues of this strategy and the underlying reaction mechanisms are discussed. The ongoing challenges and prospects in this area are critically discussed.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Lan Yuan, Ming‐Yu Qi, Zi‐Rong Tang, Yi‐Jun Xu
onlinelibrary.wiley.com/doi/10.1002/anie.202101667

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Photochemical Probe Identification of a Small‐Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)**

Photochemical Probe Identification of a Small‐Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)**

Structure‐activity relationship analysis of Hedgehog acyltransferase (HHAT) inhibitors allowed rational design of photochemical probes for HHAT. Probe photocrosslinking identified the first small‐molecule inhibitor binding site in HHAT and revealed the inhibitory mechanism, providing an optimal HHAT tool inhibitor IMP‐1575 (Ki=38 nM) for future studies.

Abstract

The mammalian membrane‐bound O‐acyltransferase (MBOAT) superfamily is involved in biological processes including growth, development and appetite sensing. MBOATs are attractive drug targets in cancer and obesity; however, information on the binding site and molecular mechanisms underlying small‐molecule inhibition is elusive. This study reports rational development of a photochemical probe to interrogate a novel small‐molecule inhibitor binding site in the human MBOAT Hedgehog acyltransferase (HHAT). Structure‐activity relationship investigation identified single enantiomer IMP‐1575, the most potent HHAT inhibitor reported to‐date, and guided design of photocrosslinking probes that maintained HHAT‐inhibitory potency. Photocrosslinking and proteomic sequencing of HHAT delivered identification of the first small‐molecule binding site in a mammalian MBOAT. Topology and homology data suggested a potential mechanism for HHAT inhibition which was confirmed by kinetic analysis. Our results provide an optimal HHAT tool inhibitor IMP‐1575 (Ki=38 nM) and a strategy for mapping small molecule interaction sites in MBOATs.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Thomas Lanyon‐Hogg, Markus Ritzefeld, Leran Zhang, Sebastian A. Andrei, Balazs Pogranyi, Milon Mondal, Lea Sefer, Callum D. Johnston, Claire E. Coupland, Jake L. Greenfield, Joshua Newington, Matthew J. Fuchter, Anthony I. Magee, Christian Siebold, Edward W. Tate
onlinelibrary.wiley.com/doi/10.1002/anie.202014457

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Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid

Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid

We report the isolation of an eunicellane‐type diterpenoid from bacteria and the first identification of a diterpene synthase and biosynthetic gene cluster responsible for the construction of the eunicellane scaffold. The absolute configurations and antibacterial activities of benditerpenoic acid and the benditerpe‐2,6,15‐triene core were established.

Abstract

A new bicyclic diterpenoid, benditerpenoic acid, was isolated from soil‐dwelling Streptomyces sp. (CL12‐4). We sequenced the bacterial genome, identified the responsible biosynthetic gene cluster, verified the function of the terpene synthase, and heterologously produced the core diterpene. Comparative bioinformatics indicated this Streptomyces strain is phylogenetically unique and possesses nine terpene synthases. The absolute configurations of the new trans‐fused bicyclo[8.4.0]tetradecanes were achieved by extensive spectroscopic analyses, including Mosher’s analysis, J‐based coupling analysis, and computations based on sparse NMR‐derived experimental restraints. Interestingly, benditerpenoic acid exists in two distinct ring‐flipped bicyclic conformations with a rotational barrier of ≈16 kcal mol−1 in solution. The diterpenes exhibit moderate antibacterial activity against Gram‐positive bacteria including methicillin and multi‐drug resistant Staphylococcus aureus. This is a rare example of an eunicellane‐type diterpenoid from bacteria and the first identification of a diterpene synthase and biosynthetic gene cluster responsible for the construction of the eunicellane scaffold.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Chenxi Zhu, Baofu Xu, Donovon A. Adpressa, Jeffrey D. Rudolf, Sandra Loesgen
onlinelibrary.wiley.com/doi/10.1002/anie.202102453

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Coating the Right Polymer: Achieving Ideal Metal–Organic Framework Particle Dispersibility in Polymer Matrixes Using a Coordinative Crosslinking Surface Modification Method

Coating the Right Polymer: Achieving Ideal Metal–Organic Framework Particle Dispersibility in Polymer Matrixes Using a Coordinative Crosslinking Surface Modification Method

A new general method for the coating of metal–organic framework (MOF) surfaces with a uniform layer of polyimide, polysulfone, polycarbonate, or polymer of intrinsic microporosity‐1 (PIM‐1) is reported. By matching the surface polymer with the matrix polymer, ideal dispersibility of MOF particles in various polymer matrices can thus be achieved.

Abstract

This work describes the first generalizable method to modify various metal–organic framework (MOF) surfaces with polyimide, polysulfone, polycarbonate, and polymer of intrinsic microporosity‐1 (PIM‐1). The method first utilizes electrostatic adsorption to rapidly decorate positively charged MOF surfaces with a layer of negatively charged metal‐organic nanocapsule, PgC5Cu. After mixing with the polymer, the copper open metal sites on PgC5Cu can coordinatively crosslink the polar functional groups on the surface polymer upon thermal activation thereby resulting in the immobilization of a uniform sub‐10 nm polymer coating. We quantitatively analyzed the distribution of free path spacing between MOF particles and demonstrated that when the surface polymer matches the matrix polymer, the MOF dispersion was not only visually improved but also found to align perfectly with a theoretically predicted ideal dispersion model where no aggregation driving force was present.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Conger Li, Junhong Liu, Kexin Zhang, Songwei Zhang, Yongjin Lee, Tao Li
onlinelibrary.wiley.com/doi/10.1002/anie.202104487

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Spatial Confinement Tunes Cleavage and Re‐Formation of C=N Bonds in Fluorescent Molecules

Spatial Confinement Tunes Cleavage and Re‐Formation of C=N Bonds in Fluorescent Molecules

Spatial confinement dramatically changes the pathway and energy profile of chemical reactions. Confinement effect promoted increased local concentration and reduced steric hindrance of reactive groups, which realized the reversible conversion of molecular fluorescence. This fluorescence switching system has potential applications in information encryption and multi‐informational display.

Abstract

Molecules in confined spaces exhibit unusual behaviors that are not typically observed in bulk systems. Such behavior can provide alternative strategies for exploring new reaction pathways. Cleavage of the C=N bond of Nile red (NR) in solution is an irreversible reaction. Here, we used spatial confinement within a cationic micelle‐confined system to convert this reaction to a reversible process. The fluorescence of NR shifted between red and green for nine cycles. The new chemical pathway based on spatial confinement can be attributed to two factors: increasing the local concentration of reactants and reducing the reaction energy barrier. This effect is supported by both experimental evidence and theoretical calculations. The cross‐linked silica shell comprising the confinement chamber stabilizes the enclosed molecules. This reduces fluorophore leakage and maintains fluorescence intensity in most environments, including in solution, on paper, and in hydrogel films, and expands practical applications in encrypted information and multi‐informational displays.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Keyan Liu, Xuezhi Qiao, Chuanhui Huang, Xiao Li, Zhenjie Xue, Tie Wang
onlinelibrary.wiley.com/doi/10.1002/anie.202103471

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A Self‐Assembled Palladium(II) Barrel for Binding of Fullerenes and Photosensitization Ability of the Fullerene‐Encapsulated Barrel

A Self‐Assembled Palladium(II) Barrel for Binding of Fullerenes and Photosensitization Ability of the Fullerene‐Encapsulated Barrel

A 1,4‐dihydropyrrolo[3,2‐b]pyrrole‐based tetra‐imidazole ligand and a PdII acceptor were employed to construct a trifacial molecular barrel (1), which acts as an efficient host for fullerenes. The barrel has better binding affinity towards C70 over C60 and predominantly encapsulates C70 from a mixture of C60/C70. In the presence of visible light, C601 and C701 show efficient photosensitizing ability for 1O2 generation.

Abstract

Fullerene extracts obtained from fullerene soot lack their real application due to their poor solubility in common solvents and difficulty in purification. Encapsulation of these extracts in a suitable host is an important approach to address these issues. We present a new Pd6 barrel (1), which is composed of three 1,4‐dihydropyrrolo[3,2‐b]pyrrole panels, clipped through six cis‐PdII acceptors. Large open windows and cavity make it an efficient host for a large guest. Favorable interactions between the ligand and fullerene (C60 and C70) allows the barrel to encapsulate fullerene efficiently. Thorough investigation reveals that barrel 1 has a stronger binding affinity towards C70 over C60, resulting in the predominant extraction of C70 from a mixture of the two. Finally, the fullerene encapsulated barrels C601 and C701 were found to be efficient for visible‐light‐induced singlet oxygen generation. Such preferential binding of C70 and photosensitizing ability of C601 and C701 are noteworthy.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Prioti Choudhury Purba, Manoranjan Maity, Soumalya Bhattacharyya, Partha Sarathi Mukherjee
onlinelibrary.wiley.com/doi/10.1002/anie.202103822

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Large‐Area Crystalline Zeolitic Imidazolate Framework Thin Films

Large‐Area Crystalline Zeolitic Imidazolate Framework Thin Films

An unconventional ZIF‐67 colloidal dispersion consisting of amorphous nanoparticles has been discovered, which was used as precursors to yield uniform films that deposited onto a number of substrates by a facile, fast, and cost‐effective spray‐coating approach, enabling fabrication of large‐area ZIF‐67 thin films with highly controlled thickness. This method can be extended to fabricate ZIF‐8 thin film.

Abstract

We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost‐effective spray‐coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low‐temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine‐doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt‐(2‐methylimidazole)2 and zinc‐(2‐methylimidazole)2 films, our findings mark a great possibility in producing other high‐quality MOF thin films on a large scale.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Zhi Chen, Rui Wang, Tao Ma, Jin‐Long Wang, Yu Duan, Zhi‐Zhan Dai, Jie Xu, Hui‐Juan Wang, Jiayin Yuan, Hai‐Long Jiang, Yue‐Wei Yin, Xiao‐Guang Li, Min‐Rui Gao, Shu‐Hong Yu
onlinelibrary.wiley.com/doi/10.1002/anie.202104366

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The Hydrotropic Effect of Ionic Liquids in Water‐in‐Salt Electrolytes**

The Hydrotropic Effect of Ionic Liquids in Water‐in‐Salt Electrolytes**

Ionic liquids boost the LiTFSI solubility in water from 21 to 60 mol kg−1. Excess lithium salt solubility arises from a hydrotropic effect of the ionic liquids. This approach improves particularly the reductive stability of water‐in‐salt electrolytes, enabling stable cycling of commercially relevant LTO/NMC811 full cells.

Abstract

Water‐in‐salt electrolytes have successfully expanded the electrochemical stability window of aqueous electrolytes beyond 2 V. Further improvements in stability can be achieved by partially substituting water with either classical organic solvents or ionic liquids. Here, we study ternary electrolytes composed of LiTFSI, water, and imidazolium ionic liquids. We find that the LiTFSI solubility strongly increases from 21 mol kg−1 in water to up to 60 mol kg−1 in the presence of ionic liquid. The solution structure is investigated with Raman and NMR spectroscopy and the enhanced LiTFSI solubility is found to originate from a hydrotropic effect of the ionic liquids. The increased reductive stability of the ternary electrolytes enables stable cycling of an aqueous lithium‐ion battery with an energy density of 150 Wh kg−1 on the active material level based on commercially relevant Li4Ti5O12 and LiNi0.8Mn0.1Co0.1O2 electrode materials.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Maximilian Becker, Daniel Rentsch, David Reber, Abdessalem Aribia, Corsin Battaglia, Ruben‐Simon Kühnel
onlinelibrary.wiley.com/doi/10.1002/anie.202103375

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Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS

Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS

The interaction between two non‐ribosomal peptide synthetase (NRPS) proteins mediates the biosynthesis of PAX peptides and involves an extended docking interface, where a part of the thiolation (T) domain and a minimal C‐terminal docking domain (CDD) cooperate to bind to the N‐terminal docking domain (NDD) with nanomolar affinity—the highest docking domain affinity yet observed in such megasynthases.

Abstract

Non‐ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N‐ and C‐terminal docking domains (N/CDDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of “designer” NRPS from proteins that normally do not interact. The multiprotein “peptide‐antimicrobial‐Xenorhabdus” (PAX) peptide‐producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small CDD of PaxA cooperates with its preceding thiolation (T1) domain to bind the NDD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Jonas Watzel, Elke Duchardt‐Ferner, Sepas Sarawi, Helge B. Bode, Jens Wöhnert
onlinelibrary.wiley.com/doi/10.1002/anie.202103498

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Structural and Mechanistic Insights into C−S Bond Formation in Gliotoxin

Structural and Mechanistic Insights into C−S Bond Formation in Gliotoxin

A combination of structural biology, mutagenesis, natural product isolation and activity assays provides insights into the formation of two carbon−sulfur bonds in the fungal virulence factor gliotoxin and related epipolythiodioxopiperazine natural products. The exceptional glutathione‐S‐transferase GliG uses an unusual bis‐hydroxylated gliotoxin precursor and successively links two molecules of glutathione.

Abstract

Glutathione‐S‐transferases (GSTs) usually detoxify xenobiotics. The human pathogenic fungus Aspergillus fumigatus however uses the exceptional GST GliG to incorporate two sulfur atoms into its virulence factor gliotoxin. Because these sulfurs are essential for biological activity, glutathionylation is a key step of gliotoxin biosynthesis. Yet, the mechanism of carbon−sulfur linkage formation from a bis‐hydroxylated precursor is unresolved. Here, we report structures of GliG with glutathione (GSH) and its reaction product cyclo[‐l‐Phe‐l‐Ser]‐bis‐glutathione, which has been purified from a genetically modified A. fumigatus strain. The structures argue for stepwise processing of first the Phe and second the Ser moiety. Enzyme‐mediated dehydration of the substrate activates GSH and a helix dipole stabilizes the resulting anion via a water molecule for the nucleophilic attack. Activity assays with mutants validate the interactions of GliG with the ligands and enrich our knowledge about enzymatic C−S bond formation in gliotoxin and epipolythiodioxopiperazine (ETP) natural compounds in general.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Kirstin Scherlach, Wolfgang Kuttenlochner, Daniel H. Scharf, Axel A. Brakhage, Christian Hertweck, Michael Groll, Eva M. Huber
onlinelibrary.wiley.com/doi/10.1002/anie.202104372

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Cluster From Cluster: A Quantitative Approach to Magic Gold Nanoclusters [Au25(SR)18]−

Cluster From Cluster: A Quantitative Approach to Magic Gold Nanoclusters [Au25(SR)18]−

A “cluster from cluster” approach was developed to assemble gold nanoclusters via preformed atomically precise Au13 precursors. This facile approach has attractive advantages: very high overall yield (≈100 %), large scale (gram‐scale) and generally applicable in the synthesis of magic cluster Au25 (10 examples).

Abstract

High‐yield and large‐scale synthesis are highly demanded for the studies of gold nanoclusters. We developed a “cluster from cluster” approach to assemble gold nanoclusters with preformed atomically precise Au13 precursors. This facile approach has proved to be very effective in the synthesis of the well‐known magic cluster [Au25(SR)18], which could prepare the target cluster in high yield (overall yield up to ≈100 %) at large scale (gram‐scale based on gold). This method can be applied in the synthesis of 10 Au25 clusters with different R groups. This work presents an important approach that may be extended to high‐yield and large‐scale synthesis of other metal nanoclusters.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Zhen Lei, Jiao‐Jiao Li, Zi‐Ang Nan, Zhan‐Guo Jiang, Quan‐Ming Wang
onlinelibrary.wiley.com/doi/10.1002/anie.202103290

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