ResearchPad - Catalysis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Late‐Stage Diversification of Tryptophan‐Derived Biomolecules]]> https://www.researchpad.co/product?articleinfo=N0b4cc56c-07df-4a4d-bcd0-9eaa878e485c

Abstract

Pd‐mediated reactions have emerged as a powerful tool for the site‐selective and bioorthogonal late‐stage diversification of amino acids, peptides and related compounds. Indole moieties of tryptophan derivatives are susceptible to C2H‐activation, whereas halogenated aromatic amino acids such as halophenylalanines or halotryptophans provide a broad spectrum of different functionalisations. The compatibility of transition‐metal‐catalysed cross‐couplings with functional groups in peptides, other biologically active compounds and even proteins has been demonstrated. This Review primarily compiles the application of different cross‐coupling reactions to modify halotryptophans, halotryptophan containing peptides or halogenated, biologically active compounds derived from tryptophan. Modern approaches use regio‐ and stereoselective biocatalytic strategies to generate halotryptophans and derivatives on a preparative scale. The combination of bio‐ and chemocatalysis in cascade reactions is given by the biocompatibility and bioorthogonality of Pd‐mediated reactions.

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<![CDATA[Synthesis of Highly Fluorinated Arene Complexes of [Rh(Chelating Phosphine)]+ Cations, and their use in Synthesis and Catalysis]]> https://www.researchpad.co/product?articleinfo=N5bf02705-1d78-491f-a090-ccdec03740a6

Abstract

The synthesis of rhodium complexes with weakly binding highly fluorinated benzene ligands is described: 1,2,3‐F3C6H3, 1,2,3,4‐F4C6H2 and 1,2,3,4,5‐F5C6H are shown to bind with cationic [Rh(Cy2P(CH2)xPCy2)]+ fragments (x=1, 2). Their structures and reactivity with alkenes, and use in catalysis for promoting the Tishchenko reaction of a simple aldehyde, are demonstrated. Key to the synthesis of these complexes is the highly concentrated reaction conditions and use of the [Al{OC(CF3)3}4] anion.

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<![CDATA[Acetylene as a Dicarbene Equivalent for Gold(I) Catalysis: Total Synthesis of Waitziacuminone in One Step]]> https://www.researchpad.co/product?articleinfo=N142732d0-ffd6-45f0-bbe2-9deb5701faa2

Abstract

The gold(I)‐catalyzed reaction of acetylene gas with alkenes leads to (Z,Z)‐1,4‐disubstituted 1,3‐butadienes and biscyclopropanes depending on the donor ligand on gold(I). Acetylene was generated in situ from calcium carbide and water in a user‐friendly procedure. Reaction of acetylene with 1,5‐dienes gives rise stereoselectively to tricyclo[5.1.0.02,4]octanes. This novel double cyclopropanation has been applied to the one step total synthesis of the natural product waitziacuminone from acetylene and geranyl acetone.

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<![CDATA[Stereochemistry of the Reaction Intermediates of Prolinol Ether Catalyzed Reactions Characterized by Vibrational Circular Dichroism Spectroscopy]]> https://www.researchpad.co/product?articleinfo=Nf7d7f78a-ea9a-4de1-9780-ad36a2645b72

Abstract

Spectroscopic characterizations of key reaction intermediates are often considered the final confirmation of a reaction mechanism. This proof‐of‐principle study showcases the application of vibrational circular dichroism (VCD) spectroscopy for the characterization of in situ generated reaction intermediates using the key intermediates of enamine catalysis of Jørgensen–Hayashi‐type prolinol ether catalysts as model system. By comparison of experimental and computed spectra, the enamines are shown to preferentially adopt an anti‐conformation with E‐configured C=C bond. For the parent prolinol catalyst, the structure and stereochemistry of the oxazolidine side product is determined as well. This study thus demonstrates that VCD spectra can provide insights into structural preferences of organocatalysts that utilize a covalent activation mechanism. Thereby it outlines new fields of applications for VCD spectroscopy and finally adds the technique to the toolbox of physical organic chemistry for in‐depth mechanistic studies.

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<![CDATA[Infrared Multiple Photon Dissociation Spectroscopy of Hydrated Cobalt Anions Doped with Carbon Dioxide CoCO 2 (H 2 O) n − , n =1–10, in the C−O Stretch Region]]> https://www.researchpad.co/product?articleinfo=Nc926e130-88c2-4f8e-8aae-cb055fa680d9

Abstract

We investigate anionic [Co,CO2,nH2O] clusters as model systems for the electrochemical activation of CO2 by infrared multiple photon dissociation (IRMPD) spectroscopy in the range of 1250–2234 cm−1 using an FT‐ICR mass spectrometer. We show that both CO2 and H2O are activated in a significant fraction of the [Co,CO2,H2O] clusters since it dissociates by CO loss, and the IR spectrum exhibits the characteristic C−O stretching frequency. About 25 % of the ion population can be dissociated by pumping the C−O stretching mode. With the help of quantum chemical calculations, we assign the structure of this ion as Co(CO)(OH)2 . However, calculations find Co(HCOO)(OH) as the global minimum, which is stable against IRMPD under the conditions of our experiment. Weak features around 1590–1730 cm−1 are most likely due to higher lying isomers of the composition Co(HOCO)(OH). Upon additional hydration, all species [Co,CO2,nH2O], n≥2, undergo IRMPD through loss of H2O molecules as a relatively weakly bound messenger. The main spectral features are the C−O stretching mode of the CO ligand around 1900 cm−1, the water bending mode mixed with the antisymmetric C−O stretching mode of the HCOO ligand around 1580–1730 cm−1, and the symmetric C−O stretching mode of the HCOO ligand around 1300 cm−1. A weak feature above 2000 cm−1 is assigned to water combination bands. The spectral assignment clearly indicates the presence of at least two distinct isomers for n ≥2.

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<![CDATA[Bis‐Cyclometalated Indazole Chiral‐at‐Rhodium Catalyst for Asymmetric Photoredox Cyanoalkylations]]> https://www.researchpad.co/product?articleinfo=Nc8ed3d4d-972e-43c1-ad80-85532cf6bc34

Abstract

A new class of bis‐cyclometalated rhodium(III) catalysts containing two inert cyclometalated 6‐tert‐butyl‐2‐phenyl‐2H‐indazole ligands and two labile acetonitriles is introduced. Single enantiomers (>99 % ee) were obtained through a chiral‐auxiliary‐mediated approach using a monofluorinated salicyloxazoline. The new chiral‐at‐metal complex is capable of catalyzing the visible‐light‐induced enantioselective α‐cyanoalkylation of 2‐acyl imidazoles in which it serves a dual function as the chiral Lewis acid catalyst for the asymmetric radical chemistry and at the same time as the photoredox catalyst for the visible‐light‐induced redox chemistry (up to 80 % yield, 4:1 d.r., and 95 % ee, 12 examples).

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<![CDATA[New Insights into the Catalytic Activity of Cobalt Orthophosphate Co3(PO4)2 from Charge Density Analysis]]> https://www.researchpad.co/product?articleinfo=Nbc1e5c01-be8e-440b-8f7b-a46aa8ea82f7

Abstract

An extensive characterization of Co3(PO4)2 was performed by topological analysis according to Bader‘s Quantum Theory of Atoms in Molecules from the experimentally and theoretically determined electron density. This study sheds light on the reactivity of cobalt orthophosphate as a solid‐state heterogeneous oxidative‐dehydration and ‐dehydrogenation catalyst. Various faces of the bulk catalyst were identified as possible reactive sites given their topological properties. The charge accumulations and depletions around the two independent five‐ and sixfold‐coordinated cobalt atoms, found in the topological analysis, are correlated to the orientation and population of the d‐orbitals. It is shown that the (011) face has the best structural features for catalysis. Fivefold‐coordinated ions in close proximity to advantageously oriented vacant coordination sites and electron depletions suit the oxygen lone pairs of the reactant, mainly for chemisorption. This is confirmed both from the multipole refinement as well as from density functional theory calculations. Nearby basic phosphate ions are readily available for C−H activation.

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<![CDATA[Merging Regiodivergent Catalysis with Atom-Economical Radical Arylation]]> https://www.researchpad.co/product?articleinfo=N3dc7120b-257c-462b-bb8c-c3321cbbe9d5

Abstract

A titanocene‐catalyzed regiodivergent radical arylation is described that allows access to either enantiomerically pure tetrahydroquinolines or indolines from a common starting material. The regioselectivity of epoxide opening that results in the high selectivity of heterocycle formation is controlled by two factors, the absolute configuration of the enantiopure ligands of the (C5H4R)2TiX2 catalyst and the inorganic ligand X (X=Cl, OTs). The overall reaction is atom‐economical and constitutes a radical Friedel–Crafts alkylation.

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<![CDATA[Study on dielectric properties of high organic sulfur coking coal and modeling sulfur compounds]]> https://www.researchpad.co/product?articleinfo=5c37b795d5eed0c48449054b

Coking coal is geologically scarce resource and most of them cannot be directly used in steel making due to their higher sulfur content. One desulfurization method that has great potential for massive application is microwave desulfurization, which removes the relatively stubborn organic sulfur under mild conditions. The dielectric properties of coals determine the efficiency of the microwave energy absorption. The key to describing the mechanism of microwave desulfurization and further improvement of the desulfurization efficiency is the dielectric response of organic sulfur compounds in coal to microwave. This study focuses on existing formand microwave response of organic sulfur components of three typical coking coal in China. Resultsshowed that the major organic sulfur in selected coals is thiophene which has a stable structure and is the most difficult to be removed. Several dielectric peaks (dielectric loss)andsignificant differencesofeach selected coal samples are observed. The microwave absorption peaks of the model sulfur compounds are identified to be within 9-11GHz. The real parts of the relative dielectric constants (hereinafter referred to as ε′) shows a decreasing trend as: diphenyl sulfoxide > diphenyl sulfone > diphenyl sulfide > dibenzothiophene > Octadecane thiol. Response to microwaveare observed to be distinctively different between sulfur-containing and sulfur-free model compounds. The dielectric polarization of mixture (coal mixed with model sulfur compounds) is greater than pure coal. Meanwhile the higher the sulfur content of the coal, the greater the ε′ is. Sulfur componentsin coal can significantly influence its polarization.

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<![CDATA[Structural insight into substrate and product binding in an archaeal mevalonate kinase]]> https://www.researchpad.co/product?articleinfo=5c12cf8ed5eed0c484914932

Mevalonate kinase (MK) is a key enzyme of the mevalonate pathway, which produces the biosynthetic precursors for steroids, including cholesterol, and isoprenoids, the largest class of natural products. Currently available crystal structures of MK from different organisms depict the enzyme in its unbound, substrate-bound, and inhibitor-bound forms; however, until now no structure has yet been determined of MK bound to its product, 5-phosphomevalonate. Here, we present crystal structures of mevalonate-bound and 5-phosphomevalonate-bound MK from Methanosarcina mazei (MmMK), a methanogenic archaeon. In contrast to the prior structure of a eukaryotic MK bound with mevalonate, we find a striking lack of direct interactions between this archaeal MK and its substrate. Further, these two MmMK structures join the prior structure of the apoenzyme to complete the first suite of structural snapshots that depict unbound, substrate-bound, and product-bound forms of the same MK. With this collection of structures, we now provide additional insight into the catalytic mechanism of this biologically essential enzyme.

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<![CDATA[Engineered Sulfur-Resistant Catalyst System with an Assisted Regeneration Strategy for Lean-Burn Methane Combustion]]> https://www.researchpad.co/product?articleinfo=5b59aca7463d7e792f619095

Abstract

Catalytic combustion of methane, the main component of natural gas, is a challenge under lean‐burn conditions and at low temperatures owing to sulfur poisoning of the Pd‐rich catalyst. This paper introduces a more sulfur‐resistant catalyst system that can be regenerated during operation. The developed catalyst system lowers the barrier that has restrained the use of liquefied natural gas as a fuel in energy production.

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<![CDATA[A modified expression of the major hydrolase activator in Hypocrea jecorina (Trichoderma reesei) changes enzymatic catalysis of biopolymer degradation]]> https://www.researchpad.co/product?articleinfo=5bcf6ad940307c74ebb862ac <![CDATA[Intramolecular N–H⋯Cl hydrogen bonds in the outer coordination sphere of a bipyridyl bisurea-based ligand stabilize a tetrahedral FeLCl2 complex]]> https://www.researchpad.co/product?articleinfo=5ba6c6fb40307c39ee105b36

A bipyridyl-bisurea ligand coordinates a tetrahedral FeCl2 complex and demonstrates secondary coordination sphere influence through intramolecular hydrogen bonding to the chloride ligands.

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<![CDATA[Kinetic Analysis of an Efficient DNA-Dependent TNA Polymerase]]> https://www.researchpad.co/product?articleinfo=5b03b68f463d7e6b556dacbf

ja-2004-028255_0001.jpgα-l-Threofuranosyl nucleoside triphosphates (tNTPs) are tetrafuranose nucleoside derivatives and potential progenitors of present-day β-d-2‘-deoxyribofuranosyl nucleoside triphosphates (dNTPs). Therminator DNA polymerase, a variant of the 9°N DNA polymerase, is an efficient DNA-directed threosyl nucleic acid (TNA) polymerase. Here we report a detailed kinetic comparison of Therminator-catalyzed TNA and DNA syntheses. We examined the rate of single-nucleotide incorporation for all four tNTPs and dNTPs from a DNA primer−template complex and carried out parallel experiments with a chimeric DNA−TNA primer−DNA template containing five TNA residues at the primer 3‘-terminus. Remarkably, no drop in the rate of TNA incorporation was observed in comparing the DNA−TNA primer to the all-DNA primer, suggesting that few primer-enzyme contacts are lost with a TNA primer. Moreover, comparison of the catalytic efficiency of TNA synthesis relative to DNA synthesis at the downstream positions reveals a difference of no greater than 5-fold in favor of the natural DNA substrate. This disparity becomes negligible when the TNA synthesis reaction mixture is supplemented with 1.25 mM MnCl2. These results indicate that Therminator DNA polymerase can recognize both a TNA primer and tNTP substrates and is an effective catalyst of TNA polymerization despite changes in the geometry of the reactants.

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<![CDATA[A Modular Approach for Assembling Aldehyde-Tagged Proteins on DNA Scaffolds]]> https://www.researchpad.co/product?articleinfo=5aeb9d92463d7e2dfdbce392

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Expansion of antibody scaffold diversity has the potential to expand the neutralizing capacity of the immune system and to generate enhanced therapeutics and probes. Systematic exploration of scaffold diversity could be facilitated with a modular and chemical scaffold for assembling proteins, such as DNA. However, such efforts require simple, modular, and site-specific methods for coupling antibody fragments or bioactive proteins to nucleic acids. To address this need, we report a modular approach for conjugating synthetic oligonucleotides to proteins with aldehyde tags at either terminus or internal loops. The resulting conjugates are assembled onto DNA-based scaffolds with low nanometer spatial resolution and can bind to live cells. Thus, this modular and site-specific conjugation strategy provides a new tool for exploring the potential of expanded scaffold diversity in immunoglobulin-based probes and therapeutics.

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<![CDATA[A Catenane Assembled through a Single Charge-Assisted Halogen Bond**]]> https://www.researchpad.co/product?articleinfo=5aeb9f27463d7e2dfdbce398 ]]> <![CDATA[N-Terminal Modification of Proteins witho-Aminophenols]]> https://www.researchpad.co/product?articleinfo=5aeacae8463d7e213636b400

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The synthetic modification of proteins plays an important role in chemical biology and biomaterials science. These fields provide a constant need for chemical tools that can introduce new functionality in specific locations on protein surfaces. In this work, an oxidative strategy is demonstrated for the efficient modification of N-terminal residues on peptides and N-terminal proline residues on proteins. The strategy uses o-aminophenols or o-catechols that are oxidized to active coupling species in situ using potassium ferricyanide. Peptide screening results have revealed that many N-terminal amino acids can participate in this reaction, and that proline residues are particularly reactive. When applied to protein substrates, the reaction shows a stronger requirement for the proline group. Key advantages of the reaction include its fast second-order kinetics and ability to achieve site-selective modification in a single step using low concentrations of reagent. Although free cysteines are also modified by the coupling reaction, they can be protected through disulfide formation and then liberated after N-terminal coupling is complete. This allows access to doubly functionalized bioconjugates that can be difficult to access using other methods.

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<![CDATA[Concerted versus Stepwise Mechanism in Thymidylate Synthase]]> https://www.researchpad.co/product?articleinfo=5aea7752463d7e1d39963bad

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Thymidylate synthase (TSase) catalyzes the intracellular de novo formation of thymidylate (a DNA building block) in most living organisms, making it a common target for chemotherapeutic and antibiotic drugs. Two mechanisms have been proposed for the rate-limiting hydride transfer step in TSase catalysis: a stepwise mechanism in which the hydride transfer precedes the cleavage of the covalent bond between the enzymatic cysteine and the product and a mechanism where both happen concertedly. Striking similarities between the enzyme-bound enolate intermediates formed in the initial and final step of the reaction supported the first mechanism, while QM/MM calculations favored the concerted mechanism. Here, we experimentally test these two possibilities using secondary kinetic isotope effect (KIE), mutagenesis study, and primary KIEs. The findings support the concerted mechanism and demonstrate the critical role of an active site arginine in substrate binding, activation of enzymatic nucleophile, and the hydride transfer studied here. The elucidation of this reduction/substitution sheds light on the critical catalytic step in TSase and may aid future drug or biomimetic catalyst design.

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<![CDATA[Structural Heterogeneity in Transmembrane Amyloid Precursor Protein Homodimer Is a Consequence of Environmental Selection]]> https://www.researchpad.co/product?articleinfo=5aea391e463d7e19a9cecd1c

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The 99 amino acid C-terminal fragment of amyloid precursor protein (C99), consisting of a single transmembrane (TM) helix, is known to form homodimers. Homodimers can be processed by γ-secretase to produce amyloid-β (Aβ) protein, which is implicated in Alzheimer’s disease (AD). While knowledge of the structure of C99 homodimers is of great importance, experimental NMR studies and simulations have produced varying structural models, including right-handed and left-handed coiled-coils. In order to investigate the structure of this critical protein complex, simulations of the C9915–55 homodimer in POPC membrane bilayer and DPC surfactant micelle environments were performed using a multiscale approach that blends atomistic and coarse-grained models. The C9915–55 homodimer adopts a dominant right-handed coiled-coil topology consisting of three characteristic structural states in a bilayer, only one of which is dominant in the micelle. Our structural study, which provides a self-consistent framework for understanding a number of experiments, shows that the energy landscape of the C99 homodimer supports a variety of slowly interconverting structural states. The relative importance of any given state can be modulated through environmental selection realized by altering the membrane or micelle characteristics.

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<![CDATA[Dph7 Catalyzes a Previously Unknown Demethylation Step in Diphthamide Biosynthesis]]> https://www.researchpad.co/product?articleinfo=5ae5dc95463d7e3bee941ee3

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Present on archaeal and eukaryotic translation elongation factor 2, diphthamide represents one of the most intriguing post-translational modifications on proteins. The biosynthesis of diphthamide was proposed to occur in three steps requiring seven proteins, Dph1–7, in eukaryotes. The functional assignments of Dph1–5 in the first and second step have been well established. Recent studies suggest that Dph6 (yeast YLR143W or human ATPBD4) and Dph7 (yeast YBR246W or human WDR85) are involved in the last amidation step, with Dph6 being the actual diphthamide synthetase catalyzing the ATP-dependent amidation reaction. However, the exact molecular role of Dph7 is unclear. Here we demonstrate that Dph7 is an enzyme catalyzing a previously unknown step in the diphthamide biosynthesis pathway. This step is between the Dph5- and Dph6-catalyzed reactions. We demonstrate that the Dph5-catalyzed reaction generates methylated diphthine, a previously overlooked intermediate, and Dph7 is a methylesterase that hydrolyzes methylated diphthine to produce diphthine and allows the Dph6-catalyzed amidation reaction to occur. Thus, our study characterizes the molecular function of Dph7 for the first time and provides a revised diphthamide biosynthesis pathway.

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