Interactions of Cellulose Model Compound D‐Cellobiose with Selected Metal Chlorides in Water: Identification of Chelating Oxygen Atoms

Interactions of Cellulose Model Compound D-Cellobiose with Selected Metal Chlorides in Water: Identification of Chelating Oxygen Atoms

A DFT study shows that metal ions prefer to approach between the two glucose rings in α/β-D-cellobiose while interacting/chelating with hydroxyl oxygen atoms of the disaccharide in aqueous medium. In the series of Li+, K+, Mg2+, Ca2+, Sn2+, Zn2+ and La3+ chlorides studied, ZnCl2 was identified as the most strongly interacting metal salt.

Abstract

Understanding interactions of metal ions with cellulose is an important step in the development of efficient catalytic methods for processing cellulose. In this study, density functional theory methods were used to identify oxygen atoms interacting or chelating with selected metal chlorides of Li+, K+, Mg2+, Ca2+, Sn2+, Zn2+ and La3+ with cellulose model compound D-cellobiose. Calculated metal-oxygen distances of energy minimized D-cellobiose : metal chloride 1 : 2 mixtures revealed that the metal ions approach between the two glucose rings in α/β-D-cellobiose, and O4, O9 are the preferred interaction/chelation points. DFT study supported a previous 13C NMR chemical shift change based experiments. ZnCl2 showing the shortest metal-oxygen distances in approach to α/β D-cellobiose is known to produce the largest 13C NMR chemical shift changes in D-cellobiose. In α-anomer, average closest metal-oxygen distances and NMR shift changes co-related at 95 % confidence interval with liner regression R2=0.8582 and Sy.x=0.5722.

Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Harshica Fernando, Ananda S. Amarasekara
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202100972

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Catalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C−COCl Bond Cleavage**

Catalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C−COCl Bond Cleavage**

Using a catalytic system comprised of Pd and Xantphos, acid chlorides can be added across strained alkenes or tethered alkynes to form two new C−C bonds via formal C−COCl cleavage. This reaction allows for a dicarbofunctionalisation in which an acid chloride group is retained in the product. DFT studies are used to rationalise a plausible pathway, while product derivatisation highlights the synthetic utility of the method.

Abstract

Here we report a palladium-catalysed difunctionalisation of unsaturated C−C bonds with acid chlorides. Formally, the C−COCl bond of an acid chloride is cleaved and added, with complete atom economy, across either strained alkenes or a tethered alkyne to generate new acid chlorides. The transformation does not require exogenous carbon monoxide, operates under mild conditions, shows a good functional group tolerance, and gives the isolated products with excellent stereoselectivity. The intermolecular reaction tolerates both aryl- and alkenyl-substituted acid chlorides and is successful when carboxylic acids are transformed to the acid chloride in situ. The reaction also shows an example of temperature-dependent stereodivergence which, together with plausible mechanistic pathways, is investigated by DFT calculations. Moreover, we show that benzofurans can be formed in an intramolecular variant of the reaction. Finally, derivatisation of the products from the intermolecular reaction provides a highly stereoselective approach for the synthesis of tetrasubstituted cyclopentanes.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Elliott H. Denton, Yong Ho Lee, Sven Roediger, Philip Boehm, Maximilian Fellert, Bill Morandi
onlinelibrary.wiley.com/doi/10.1002/anie.202108818

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Rational Design of Sustainable Liquid Microcapsules for Spontaneous Fragrance Encapsulation

Rational Design of Sustainable Liquid Microcapsules for Spontaneous Fragrance Encapsulation

The use of a PEG-g-PVAc amphiphilic graft copolymer together with hydrophobic fragrances in aqueous medium leads to the spontaneous formation of colloidally stable suspensions of liquid coacervate droplets. Arrows indicate the local turbulences sustaining the spontaneous mixing of the components. The bottom panel shows the confocal Raman microspectroscopy mapping of a multicompartment coacervate droplet with carvone as fragrance.

Abstract

The high volatility, water-immiscibility, and light/oxygen-sensitivity of most aroma compounds represent a challenge to their incorporation in liquid consumer products. Current encapsulation methods entail the use of petroleum-based materials, initiators, and crosslinkers as well as mixing, heating, and purification steps. Hence, more efficient and eco-friendly approaches to encapsulation must be sought. Herein, we propose a simple method by making use of a pre-formed amphiphilic polymer and employing the Hansen Solubility Parameters approach to determine which fragrances could be encapsulated by spontaneous coacervation in water. The coacervates do not precipitate as solids but they remain suspended as colloidally stable liquid microcapsules, as demonstrated by fluorescence correlation spectroscopy. The effective encapsulation of fragrance is proven through confocal Raman spectroscopy, while the structure of the capsules is investigated by means of cryo FIB/SEM, confocal laser scanning microscopy, and small-angle X-ray scattering.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Marianna Mamusa, Rosangela Mastrangelo, Tom Glen, Sergio Murgia, Gerardo Palazzo, Johan Smets, Piero Baglioni
onlinelibrary.wiley.com/doi/10.1002/anie.202110446

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Synthesis of Mixed‐Valent Lanthanide Sulfide Nanoparticles

Synthesis of Mixed-Valent Lanthanide Sulfide Nanoparticles

Using divalent lanthanide halides with bis(trimethylsilyl)sulfide and oleylamine, the mixed-valent ferromagnets Eu3S4 and EuSm2S4; and EuS, SmS1.9, and Sm3S4 were prepared. The phase is influenced by the halide and the reaction temperature, where EuCl2 formed EuS while EuI2 formed Eu3S4, highlighting the role of kinetics in phase stabilization. Interestingly, at lower temperatures EuI2 initially forms EuS, and converts over time to Eu3S4.

Abstract

In targeting reduced valent lanthanide chalcogenides, we report the first nanoparticle synthesis of the mixed-valent ferromagnets Eu3S4 and EuSm2S4. Using divalent lanthanide halides with bis(trimethylsilyl)sulfide and oleylamine, we prepared nanoparticles of EuS, Eu3S4, EuSm2S4, SmS1.9, and Sm3S4. All nanoparticle phases were identified using powder X-ray diffraction, transmission electron microscopy was used to confirm morphology and nanoparticle size, and magnetic susceptibility measurements for determining the ordering temperatures and valence. The UV/Vis, Raman and X-ray photoelectron spectroscopies for each phase were compared. Surprisingly, the phase is influenced by the halide and the reaction temperature, where EuCl2 formed EuS while EuI2 formed Eu3S4, highlighting the role of kinetics in phase stabilization. Interestingly, at lower temperatures EuI2 initially forms EuS, and converts over time to Eu3S4.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Priscilla Glaser, Orlando Stewart, Rida Atif, Dane Romar C. Asuigui, Joel Swanson, Adam J. Biacchi, Angela R. Hight Walker, Gregory Morrison, Hans‐Conrad Loye, Sarah L. Stoll
onlinelibrary.wiley.com/doi/10.1002/anie.202108993

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Hierarchically Porous Metal–Organic Framework/MoS2 Interface for Selective Photocatalytic Conversion of CO2 with H2O into CH3COOH

Hierarchically Porous Metal–Organic Framework/MoS2 Interface for Selective Photocatalytic Conversion of CO2 with H2O into CH3COOH

MoS2 nanosheets were integrated into a hierarchically porous defective MOF UiO-66. The unsaturated Mo atoms in MoS2 sheets rationally regulate contact interfaces with Zr6O4(OH)4 nodes to form Mo-O-Zr bimetallic sites. The Mo-O-Zr bimetallic sites at the interfaces allows photo-catalytic conversion of gas phase CO2 and H2O into CH3COOH and O2.

Abstract

Metal–organic frameworks (MOFs) provide a platform to design new heterogeneous catalysts for catalytic CO2 reduction, but selective formation of C2 valuable liquid fuel products remains a challenge. Herein, we propose a strategy to synthesize composites by integrating MoS2 nanosheets into hierarchically porous defective UiO-66 (d-UiO-66) to form Mo-O-Zr bimetallic sites on the interfaces between UiO-66 and MoS2. The active interfaces are favorable for the efficient transfer of photo-generated charge carriers and for promoting the activity, whereas, the synergy of the components at the interfaces achieves selectivity for C2 production. The d-UiO-66/MoS2 composite facilitates the photo-catalytic conversion of gas phase CO2 and H2O to CH3COOH under visible light irradiation without any other adducts. The evolution rate and selectivity of CH3COOH reached 39.0 μmol g−1 h−1 and 94 %, respectively, without any C1 products, suggesting a new approach for the design of highly efficient photocatalysts of CO2 for C2 production. Theoretical calculations demonstrate the charge-polarized Zr-O-Mo aided the C−C coupling process with the largely reduced energy barrier.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Fengyang Yu, Xu Jing, Yao Wang, Mingyang Sun, Chunying Duan
onlinelibrary.wiley.com/doi/10.1002/anie.202108892

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Discovery and Characterisation of Highly Cooperative FAK‐Degrading PROTACs

Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs

A PROTAC with an unusually short linker potently degrades focal adhesion kinase (FAK). SPR and X-ray crystallography revealed a highly cooperative FAK-PROTAC-VCB ternary complex, and FAK degradation showed enhanced effects on 3D cell growth compared to FAK inhibitors. In mice, GSK215 induced rapid and sustained degradation of FAK with a profound PK/PD disconnect.

Abstract

Focal adhesion kinase (FAK) is a key mediator of tumour progression and metastasis. To date, clinical trials of FAK inhibitors have reported disappointing efficacy for oncology indications. We report the design and characterisation of GSK215, a potent, selective, FAK-degrading Proteolysis Targeting Chimera (PROTAC) based on a binder for the VHL E3 ligase and the known FAK inhibitor VS-4718. X-ray crystallography revealed the molecular basis of the highly cooperative FAK-GSK215-VHL ternary complex, and GSK215 showed differentiated in-vitro pharmacology compared to VS-4718. In mice, a single dose of GSK215 induced rapid and prolonged FAK degradation, giving a long-lasting effect on FAK levels (≈96 h) and a marked PK/PD disconnect. This tool PROTAC molecule is expected to be useful for the study of FAK-degradation biology in vivo, and our results indicate that FAK degradation may be a differentiated clinical strategy versus FAK inhibition for the treatment of cancer.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Robert P. Law, Joao Nunes, Chun‐wa Chung, Marcus Bantscheff, Karol Buda, Han Dai, John P. Evans, Adam Flinders, Diana Klimaszewska, Antonia J. Lewis, Marcel Muelbaier, Paul Scott‐Stevens, Peter Stacey, Christopher J. Tame, Gillian F. Watt, Nico Zinn, Markus A. Queisser, John D. Harling, Andrew B. Benowitz
onlinelibrary.wiley.com/doi/10.1002/anie.202109237

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Direct Access to α‐Aminosilanes Enabled by Visible‐Light‐Mediated Multicomponent Radical Cross‐Coupling

Direct Access to α-Aminosilanes Enabled by Visible-Light-Mediated Multicomponent Radical Cross-Coupling

Direct cross-coupling of organo(tristrimethylsilyl)silanes with alkylamine and aldehyde feedstocks has been achieved. A wide range of highly functionalized α-aminosilanes can be obtained with generally good yields and optically pure α-aminosilanes are accessible with excellent stereocontrol. This method provides a novel disconnection strategy for the synthesis of a diverse range of α-aminosilanes.

Abstract

α-Aminosilanes are an important class of organic compounds that show biological activity. In this communication, a new approach to α-aminosilanes that utilizes photoredox catalysis to enable three-component coupling of organo(tristrimethylsilyl)silanes with feedstock alkylamines and aldehydes is presented. A wide range of highly functionalized α-aminosilanes can be obtained in good yields under mild conditions. Both primary amines and secondary amines are compatible with this transformation. Moreover, optically pure α-aminosilanes are accessible by using chiral amines. Mechanistic studies indicate that reactions proceed through radical/radical cross-coupling of silyl radicals with α-amino alkyl radicals.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Xiaoye Yu, Constantin G. Daniliuc, Fatmah Ali Alasmary, Armido Studer
onlinelibrary.wiley.com/doi/10.1002/anie.202109252

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Biocatalytic C3‐Indole Methylation—A Useful Tool for the Natural‐Product‐Inspired Stereoselective Synthesis of Pyrroloindoles

Biocatalytic C3-Indole Methylation—A Useful Tool for the Natural-Product-Inspired Stereoselective Synthesis of Pyrroloindoles

Utilizing the promiscuous C3-indole methyl transferase PsmD enabled the enantioselective synthesis of various pyrroloindolines. By additionally applying the halo methyl transferase CtHMT not only the expensive SAM cofactor could be recycled, but also the enzymatic preparative scale transformation was achieved.

Abstract

Enantioselective synthesis of bioactive compounds bearing a pyrroloindole framework is often laborious. In contrast, there are several S-adenosyl methionine (SAM)-dependent methyl transferases known for stereo- and regioselective methylation at the C3 position of various indoles, directly leading to the formation of the desired pyrroloindole moiety. Herein, the SAM-dependent methyl transferase PsmD from Streptomyces griseofuscus, a key enzyme in the biosynthesis of physostigmine, is characterized in detail. The biochemical properties of PsmD and its substrate scope were demonstrated. Preparative scale enzymatic methylation including SAM regeneration was achieved for three selected substrates after a design-of-experiment optimization.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Pascal Schneider, Birgit Henßen, Beatrix Paschold, Benjamin P. Chapple, Marcel Schatton, Florian P. Seebeck, Thomas Classen, Jörg Pietruszka
onlinelibrary.wiley.com/doi/10.1002/anie.202107619

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Sustainable Pd(OAc)2/Hydroquinone Cocatalyst System for Cis‐Selective Dibenzoyloxylation of 1,3‐Cyclohexadiene

Sustainable Pd(OAc)2/Hydroquinone Cocatalyst System for Cis-Selective Dibenzoyloxylation of 1,3-Cyclohexadiene

We report an efficient and scalable cis-selective diacyloxylation protocol that employs catalytic hydroquinone with tBuOOH as a benign terminal oxidant. A bromide additive was crucial to obtaining good yields and excellent cis selectivity. The study culminates in the implementation of the optimized reaction on large scale.

Abstract

The 1,4-diacyloxylation of 1,3-cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing cis-selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2, which limit process sustainability and large-scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ with tert-butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch from trans to cis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports high cis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large-scale applications.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Alexios G. Stamoulis, Peng Geng, Michael A. Schmidt, Martin D. Eastgate, Alina Borovika, Kenneth J. Fraunhoffer, Shannon S. Stahl
onlinelibrary.wiley.com/doi/10.1002/anie.202108499

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A Copper(I) Complex with Two Unpaired Electrons, Synthesised by Oxidation of a Copper(II) Complex with Two Redox‐Active Ligands

A Copper(I) Complex with Two Unpaired Electrons, Synthesised by Oxidation of a Copper(II) Complex with Two Redox-Active Ligands

Oxidation-induced reduction: The oxidation of mononuclear CuII complexes with novel unsymmetric redox-active urea azine or thio-urea azine ligands leads to metal reduction and formation of complexes with intriguing electronic structures. The stability in several redox states is the basis for their first application in catalytic aerobic alcohol oxidation.

Abstract

Two homoleptic copper(II) complexes [Cu(L1)2] and [Cu(L2)2] with anionic redox-active ligands were synthesised, one with urea azine (L1) and the other with thio-urea azine (L2) ligands. One-electron oxidation of the complexes initiates an unprecedented redox-induced electron transfer process, leading to monocationic copper(I) complexes [Cu(L1)2]+ and [Cu(L2)2]+ with two oxidised ligands. While [Cu(L1)2]+ is best described as a CuI complex with two neutral radical ligands that couple antiferromagnetically, [Cu(L2)2]+ is a CuI complex with two clearly different ligand units in the solid state and with a magnetic susceptibility close to a diamagnetic compound. Further one-electron oxidation of the complex with L1 ligands results in a dication [Cu(L1)2]2+, best described as a CuI complex with a twofold oxidised, monocationic ligand and a neutral radical ligand. The stability in at least three redox states, the accumulation of spin density at the ligands and the facile ligand-metal electron transfer make these complexes highly attractive for a variety of applications; here the catalytic aerobic oxidation of alcohols to aldehydes is tested.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Marco Werr, Elisabeth Kaifer, Markus Enders, Andika Asyuda, Michael Zharnikov, Hans‐Jörg Himmel
onlinelibrary.wiley.com/doi/10.1002/anie.202109367

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Li2MTeO6 (M=Ti, Sn): Mid‐Infrared Nonlinear Optical Crystal with Strong Second Harmonic Generation Response and Wide Transparency Range

Li2MTeO6 (M=Ti, Sn): Mid-Infrared Nonlinear Optical Crystal with Strong Second Harmonic Generation Response and Wide Transparency Range

New tellurate LTT and LST crystals were obtained by a TSSG method with a broad transparent region of 0.38–6.72 and 0.38–6.86 μm for MIR NLO applications. Both LTT and LST belong to the space group Pnn2, with an almost identical structure. The LTT crystal exhibits intense powder SHG response. First-principles calculations and dipole moments were used to illustrate the results of the powder SHG based on the crystal structures.

Abstract

Oxide crystals have been widely used in nonlinear optics (NLO) in the ultraviolet–visible and near-infrared regions. Most traditional oxide crystals are restricted to the mid-infrared region due to their narrow transmission window. Hence, attempting to extend infrared cutoff wavelength of oxides has attracted much attention. Herein, we report two new tellurates Li2TiTeO6 (LTT) and Li2SnTeO6 (LST) with broad transparent regions of 0.38–6.72 and 0.38–6.86 μm, respectively, as excellent candidates for mid-infrared NLO applications. Both LTT and LST crystallize in the orthorhombic space group Pnn2. The LTT crystal exhibits intense powder second-order generation efficiency (26×KDP) under the fundamental wavelength of 1064 nm. First-principles calculations and dipole moments were used to illustrate the results of the powder second-harmonic generations based on the crystal structures. Our results provide a novel oxide NLO crystal with a strong SHG and wide transparency range. They also pave a way for the design of new oxide mid-IR NLO crystals.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Xiaoli Du, Xiaojie Guo, Zeliang Gao, Fuan Liu, Feifei Guo, Siyuan Wang, Haoyuan Wang, Youxuan Sun, Xutang Tao
onlinelibrary.wiley.com/doi/10.1002/anie.202108978

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PtSe2/Pt Heterointerface with Reduced Coordination for Boosted Hydrogen Evolution Reaction

PtSe2/Pt Heterointerface with Reduced Coordination for Boosted Hydrogen Evolution Reaction

Ultra-small Pt particles are generated in situ on the surface of PtSe2 nanosheet with Se vacancies for enhanced hydrogen evolution reaction.

Abstract

PtSe2 is a typical noble metal dichalcogenide (NMD) that holds promising possibility for next-generation electronics and photonics. However, when applied in hydrogen evolution reaction (HER), it exhibits sluggish kinetics due to the insufficient capability of absorbing active species. Here, we construct PtSe2/Pt heterointerface to boost the reaction dynamics of PtSe2, enabled by an in situ electrochemical method. It is found that Se vacancies are induced around the heterointerface, reducing the coordination environment. Correspondingly, the exposed Pt atoms at the very vicinity of Se vacancies are activated, with enhanced overlap with H 1s orbital. The adsorption of H. intermediate is thus strengthened, achieving near thermoneutral free energy change. Consequently, the as-prepared PtSe2/Pt exhibits extraordinary HER activity even superior to Pt/C, with an overpotential of 42 mV at 10 mA cm−2 and a Tafel slope of 53 mV dec−1. This work raises attention on NMDs toward HER and provides insights for the rational construction of novel heterointerfaces.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Zongpeng Wang, Beibei Xiao, Zhiping Lin, Yaping Xu, Yan Lin, Fanqi Meng, Qinghua Zhang, Lin Gu, Baizeng Fang, Shaojun Guo, Wenwu Zhong
onlinelibrary.wiley.com/doi/10.1002/anie.202110335

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Designing Anion‐Type Water‐Free Zn2+ Solvation Structure for Robust Zn Metal Anode

Designing Anion-Type Water-Free Zn2+ Solvation Structure for Robust Zn Metal Anode

We propose an anion-type water-free Zn2+ solvation structure electrolyte for developing a Zn metal anode. The chloride salt with bulky cations unlocks the Zn2+-water interactions, and a new solvation structure-ZnCl42− is formed without bound water. Owing to the limited hydrogen evolution reaction and the electrostatic repulsion between Zn tips and anion, the electrolyte shows an average Zn plating/stripping CE of ≈99.9 % and uniform Zn deposition.

Abstract

Rechargeable aqueous Zn batteries are potential for large-scale electrochemical energy storage due to their low cost and high security. However, Zn metal anode suffers from the dendritic growth and interfacial hydrogen evolution reaction (HER), resulting in the deterioration of electrode/battery performance. Here we propose that both dendrites and HER are related to the water participated Zn2+ solvation structure-Zn(H2O)62+ and thus can be resolved by transforming Zn(H2O)62+ to an anion-type water-free solvation structure-ZnCl42−, which is achieved in traditional ZnSO4 aqueous electrolyte after adding chloride salt with a bulky cation (1-ethyl-3-methylimidazolium chloride). The elimination of cation-water interaction suppresses HER, while the electrostatic repulsion between Zn tips and the anion solvation structure inhibits dendrite formation. As a result, the electrolyte shows uniform Zn deposition with an average Zn plating/stripping Coulombic efficiency of ≈99.9 %, enabling a capacity retention of 78.8 % after 300 cycles in anode-free Zn batteries with pre-zincificated polyaniline as the cathode. This work provides a novel electrolyte design strategy to prevent HER and realize long-lifespan metal anode.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Qiu Zhang, Yilin Ma, Yong Lu, Xunzhu Zhou, Liu Lin, Lin Li, Zhenhua Yan, Qing Zhao, Kai Zhang, Jun Chen
onlinelibrary.wiley.com/doi/10.1002/anie.202109682

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Selective Detection of Cu+ Ions in Live Cells via Fluorescence Lifetime Imaging Microscopy

Selective Detection of Cu+ Ions in Live Cells via Fluorescence Lifetime Imaging Microscopy

Herein we report a new fluorescent probe that upon binding to copper(I) (but not any other physiologically relevant metal ions), displays an intensity switch-on as well as a significant change in its fluorescence lifetime. The later has allowed us to visualize copper(I) in live cells via fluorescence lifetime imaging microscopy.

Abstract

Copper is an essential trace element in living organisms with its levels and localisation being carefully managed by the cellular machinery. However, if misregulated, deficiency or excess of copper ions can lead to several diseases. Therefore, it is important to have reliable methods to detect, monitor and visualise this metal in cells. Herein we report a new optical probe based on BODIPY, which shows a switch-on in its fluorescence intensity upon binding to copper(I), but not in the presence of high concentration of other physiologically relevant metal ions. More interestingly, binding to copper(I) leads to significant changes in the fluorescence lifetime of the new probe, which can be used to visualize copper(I) pools in lysosomes of live cells via fluorescence lifetime imaging microscopy (FLIM).

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Martin Priessner, Peter A. Summers, Benjamin W. Lewis, Magdalena Sastre, Liming Ying, Marina K. Kuimova, Ramon Vilar
onlinelibrary.wiley.com/doi/10.1002/anie.202109349

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Topochemical Ene–Azide Cycloaddition Reaction

Topochemical Ene–Azide Cycloaddition Reaction

The rationally designed monomer having reactive groups, azide and alkene, adopts suitable crystal packing for a novel topochemical ene–azide cycloaddition reaction (TEAC). Spontaneously, the monomer undergoes polymerization to yield triazoline-linked polymer in a single-crystal-to-single-crystal fashion. The triazoline-linked polymer is transformed into a value-added aziridine-linked polymer by simple heating.

Abstract

Topochemical reactions, high-yielding solid-state reactions arising from the proximal alignment of reacting partners in the crystal lattice, do not require solvents, catalysts, and additives, are of high demand in the context of green processes and environmental safety. However, the bottleneck is the limited number of reactions that can be done in the crystal medium. We present the topochemical ene–azide cycloaddition (TEAC) reaction, wherein alkene and azide groups undergo lattice-controlled cycloaddition reaction giving triazoline in crystals. A designed monomer that arranges in a head-to-tail manner in its crystals pre-organizing the reacting groups of adjacent molecules in proximity undergoes spontaneous cycloaddition reaction in a single-crystal-to-single-crystal fashion, yielding the triazoline-linked polymer. A unique advantage of this reaction is that the triazoline can be converted to aziridine by simple heating, which we exploited for the otherwise challenging post-synthetic backbone modification of the polymer. This reaction may revolutionize the field of polymer science.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Ravichandran Khazeber, Kana M. Sureshan
onlinelibrary.wiley.com/doi/10.1002/anie.202109344

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Asymmetric Cation‐Olefin Monocyclization by Engineered Squalene–Hopene Cyclases

Asymmetric Cation-Olefin Monocyclization by Engineered Squalene–Hopene Cyclases

The intrinsic capability of squalene–hopene cyclases to convert (E)- or (Z)-substrates enantiospecifically to (S)- or (R)-configurated monocyclic terpenoids was put into action by a combination of enzyme evolution and substrate engineering for the synthesis of (S)- and (R)-γ-dihydroionone with >99 % ee.

Abstract

Squalene–hopene cyclases (SHCs) have great potential for the industrial synthesis of enantiopure cyclic terpenoids. A limitation of SHC catalysis has been the enzymes’ strict (S)-enantioselectivity at the stereocenter formed after the first cyclization step. To gain enantio-complementary access to valuable monocyclic terpenoids, an SHC-wild-type library including 18 novel homologs was set up. A previously not described SHC (AciSHC) was found to synthesize small amounts of monocyclic (R)-γ-dihydroionone from (E/Z)-geranylacetone. Using enzyme and process optimization, the conversion to the desired product was increased to 79 %. Notably, analyzed AciSHC variants could finely differentiate between the geometric geranylacetone isomers: While the (Z)-isomer yielded the desired monocyclic (R)-γ-dihydroionone (>99 % ee), the (E)-isomer was converted to the (S,S)-bicyclic ether (>95 % ee). Applying the knowledge gained from the observed stereodivergent and enantioselective transformations to an additional SHC-substrate pair, access to the complementary (S)-γ-dihydroionone (>99.9 % ee) could be obtained.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Michael Eichenberger, Sean Hüppi, David Patsch, Natalie Aeberli, Raphael Berweger, Sandro Dossenbach, Eric Eichhorn, Felix Flachsmann, Lucas Hortencio, Francis Voirol, Sabine Vollenweider, Uwe T. Bornscheuer, Rebecca Buller
onlinelibrary.wiley.com/doi/10.1002/anie.202108037

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Muonium Addition to a peri‐Trifluoromethylated 9‐Phosphaanthracene Producing a High‐Energy Paramagnetic π‐Conjugated Fused Heterocycle

Muonium Addition to a peri-Trifluoromethylated 9-Phosphaanthracene Producing a High-Energy Paramagnetic π-Conjugated Fused Heterocycle

Muon spin rotation/resonance (μSR) studies for 10-mesityl-1,8-bis(trifluromethyl)-9-phosphaanthracene visualized a paramagnetic species produced by addition of muonium (Mu). DFT calculations for the P-muoniation product suggested two isomers, and the metastable conformer including the almost planar fused tricyclic unit simulated the experimental hfcs. The metastable structure is promoted by the larger zero-point energy due to light muon (μ+).

Abstract

In this communication, we report muon spin rotation/resonance (μSR) studies for understanding radical reactivity of 10-mesityl-1,8-bis(trifluoromethyl)-9-phosphaanthracene. Transverse-field muon spin rotation (TF-μSR) and muon avoided level-crossing resonance (μLCR) measurements successfully visualized a paramagnetic species produced by regioselective addition of muonium (Mu) to the skeletal phosphorus atom. Density functional theory (DFT) calculations for the P-muoniation product suggested two possible isomers. Whereas the most stable isomer including the envelope-type phosphorus heterocycle shows considerably different hyperfine coupling constants (hfcs) from those of the TF-μSR and μLCR, the metastable structure accompanying the almost planar tricyclic π-conjugated skeleton could simulate the experimentally determined hfcs. The metastable planar π-conjugated paramagnetic tricyclic-fused skeleton is promoted by the larger zero-point energy due to the light muon (μ+), one ninth of the proton mass.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Kota Koshino, Kenji M. Kojima, Iain McKenzie, Shigekazu Ito
onlinelibrary.wiley.com/doi/10.1002/anie.202109784

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Chemoselective and Highly Sensitive Quantification of Gut Microbiome and Human Metabolites

Chemoselective and Highly Sensitive Quantification of Gut Microbiome and Human Metabolites

Chemoselective probes based on stable isotope labeling allow for highly sensitive mass spectrometric quantification and detection of metabolites at attomole quantities in three human sample types.

Abstract

The microbiome has a fundamental impact on the human host’s physiology through the production of highly reactive compounds that can lead to disease development. One class of such compounds are carbonyl-containing metabolites, which are involved in diverse biochemical processes. Mass spectrometry is the method of choice for analysis of metabolites but carbonyls are analytically challenging. Herein, we have developed a new chemical biology tool using chemoselective modification to overcome analytical limitations. Two isotopic probes allow for the simultaneous and semi-quantitative analysis at the femtomole level as well as qualitative analysis at attomole quantities that allows for detection of more than 200 metabolites in human fecal, urine and plasma samples. This comprehensive mass spectrometric analysis enhances the scope of metabolomics-driven biomarker discovery. We anticipate that our chemical biology tool will be of general use in metabolomics analysis to obtain a better understanding of microbial interactions with the human host and disease development.

Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Weifeng Lin, Louis P. Conway, Miroslav Vujasinovic, J.‐Matthias Löhr, Daniel Globisch
onlinelibrary.wiley.com/doi/10.1002/anie.202107101

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One‐Pot Synthesis of Pyrrolo[1,2‐f]phenanthridines From 1‐Arylpyrroles via Successive Palladium‐Catalyzed Direct Arylations

One-Pot Synthesis of Pyrrolo[1,2-f]phenanthridines From 1-Arylpyrroles via Successive Palladium-Catalyzed Direct Arylations

A wide variety of pyrrolo[1,2-f]phenanthridines can be obtained from commercially available compounds using only 2 mol% of easily available Pd(OAc)2 catalyst precursor and KOAc as inexpensive base. With this synthetic scheme, the introduction of desired functional groups at positions 5, 6, 7, 8, 10 and 11 of pyrrolo[1,2-f]phenanthridines is possible.

Abstract

A Pd-catalyzed annulative π-extension reaction of 1-arylpyrroles using 1,2-dihalobenzenes as the coupling partners was investigated. The higher reactivity of pyrrole C2−H bond compared to C−H bonds of the aryl unit of 1-arylpyrroles allows selective synthesis of pyrrolo[1,2-f]phenanthridines via successive palladium-catalyzed direct intermolecular followed by intramolecular direct arylation steps. From 1-bromo-2-iodobenzenes bearing substituents at C4- or C5-positions and ortho-, meta– or para-substituted 1-arylpyrroles, the access to pyrrolo[1,2-f]phenanthridines containing substituents at C5, C6, C7, C8, C10 and/or C11 positions is possible.

Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Jian Zhang, Xinzhe Shi, Henri Doucet
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202100766

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Rhodium‐Catalyzed [4+2] Annulation of N‐Aryl Pyrazolones with Diazo Compounds To Access Pyrazolone‐Fused Cinnolines

Rhodium-Catalyzed [4+2] Annulation of N-Aryl Pyrazolones with Diazo Compounds To Access Pyrazolone-Fused Cinnolines

An efficient synthesis of novel dinitrogen-fused heterocycles, such as pyrazolo[1,2-a]cinnoline derivatives, has been accomplished by the rhodium(III)-catalyzed reaction of N-arylpyrazol-5-ones with diazo compounds. This reaction proceeds through a cascade C−H activation/intramolecular cyclization under mild reaction conditions and features a broad substrate scope.

Abstract

An efficient synthesis of novel dinitrogen-fused heterocycles such as pyrazolo[1,2-a]cinnoline derivatives have been accomplished by the rhodium(III)-catalyzed reaction of N-arylpyrazol-5-ones with α-diazo compounds. This reaction proceeds through a cascade C−H activation/intramolecular cyclization with a broad substrate scope. Furthermore, this protocol is successfully extended to the unusual phosphorus-containing α-diazo compounds and cyclic diazo compounds as the cross-coupling partners to deliver the two new kinds of pyrazolo[1,2-a]cinnolinones. The control experiments were performed to reveal insight into the mechanism of this reaction, involving reversible C−H activation, migratory insertion of the diazo compound, and cascade cyclization as the key steps of the transformation. Moreover, gram-scale synthesis and further transformation of the target product demonstrate the synthetic utility of the present protocol.

Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Chih‐Yu Lin, Wan‐Wen Huang, Ying‐Ti Huang, Sandip Dhole, Chung‐Ming Sun
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202101005

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Synthesis and Properties of Oligonucleotides Containing 2′‐O,4′‐C‐Ethylene‐Bridged 5‐Methyluridine with Exocyclic Methylene and Methyl Groups in the Bridge

Synthesis and Properties of Oligonucleotides Containing 2′-O,4′-C-Ethylene-Bridged 5-Methyluridine with Exocyclic Methylene and Methyl Groups in the Bridge

Oligonucleotides containing 6′-methylene-ENA and 6′R-Me-ENA were synthesized and their properties (duplex-forming ability toward ssRNA and ssDNA, triplex-forming ability toward dsDNA, thermodynamic parameters, and enzymatic stability) were investigated. The thermal stabilities of 6′-methylene-ENA- and 6′R-Me-ENA-modified oligonucleotides when complexes with ssRNA and dsDNA under molecular crowding conditions were also examined.

Abstract

Novel 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) analogs with exocyclic methylene and (R)-methyl groups at the 6′-position were synthesized. The obtained 6′-methylene-ENA and 6′R-Me-ENA were incorporated into oligonucleotides, and their properties were compared with those of the corresponding natural, ENA-, and 6′S-Me-ENA-modified oligonucleotides. The duplex-stabilizing ability of 6′-methylene-ENA and 6′R-Me-ENA with single-stranded RNA (ssRNA) was similar to that of ENA and 6′S-Me-ENA under both dilute and molecular crowding conditions. On the other hand, oligonucleotides containing 6′-methylene-ENA and 6′R-Me-ENA formed stable triplexes with double-stranded DNA (dsDNA) in comparison with those containing 6′S-Me-ENA. Their thermodynamic properties were also calculated to explore the influence of the substituents introduced at the 6′-position of ENA. Moreover, oligonucleotides with ENA analogs exhibited excellent resistance against nucleases. These results suggest that 6′-methylene-ENA and 6′R-Me-ENA are promising candidates for targeting ssRNA and dsDNA.

Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Yuta Ito, Kodai Nishida, Norika Tsutsui, Yasufumi Fuchi, Yoshiyuki Hari
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202100947

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Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

Gram-Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

By using solvent-less techniques such as ball milling, a hexapeptide was synthesized in gram scale without using any toxic solvents. To date, this hexapeptide is the largest precisely controlled amino acid sequence ever synthesized in a ball mill. This study paves the way to future developments for the synthesis of longer peptides (and proteins) by using ball milling.

Abstract

Synthesis of long peptides is generally considered as a challenge to peptide chemists, in addition to producing significant amounts of toxic waste, such as DMF. Here we show that using solvent-less methods, such as ball milling, enabled the production of the hexapeptide Boc-(Ala-Phe-Gly)2-OBn at the gram scale with high overall yield (77 %, 5 linear steps). This is the longest peptide chain synthesized in a ball mill to date, in which the amino acid sequence is precisely controlled. This study complements the current fundamental knowledge required to synthesize longer and more difficult peptide chains (or small proteins) by using peptide fragment couplings in a ball mill.

Wiley: European Journal of Organic Chemistry: Table of Contents
Authors: Yves Yeboue, Nadia Rguioueg, Gilles Subra, Jean Martinez, Frédéric Lamaty, Thomas‐Xavier Métro
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202100839

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