pinecone/core-2020-05-10-deduplication huggingface dataset:
A Synthetic DNA-Binding Domain Guides Distinct Chromatin-Modifying Small Molecules to Activate an Identical Gene Network

Synthetic dual‐function ligands targeting specific DNA sequences and histone‐modifying enzymes were applied to achieve regulatory control over multi‐gene networks in living cells. Unlike the broad array of targeting small molecules for histone deacetylases (HDACs), few modulators are known for histone acetyltransferases (HATs), which play a central role in transcriptional control. As a novel chemical approach to induce selective HAT‐regulated genes, we conjugated a DNA‐binding domain (DBD) “I” to N‐(4‐chloro‐3‐trifluoromethyl‐phenyl)‐2‐ethoxy‐benzamide (CTB), an artificial HAT activator. In vitro enzyme activity assays and microarray studies were used to demonstrate that distinct functional small molecules could be transformed to have identical bioactivity when conjugated with a targeting DBD. This proof‐of‐concept synthetic strategy validates the switchable functions of HDACs and HATs in gene regulation and provides a molecular basis for developing versatile bioactive ligands
Transition-Metal-Free Synthesis of Carbazoles and Indoles by an SN Ar-Based "Aromatic Metamorphosis" of Thiaarenes.

Dibenzothiophene dioxides, which are readily prepared through oxidation of the parent dibenzothiophenes, undergo nucleophilic aromatic substitution with anilines intermolecularly and then intramolecularly to yield the corresponding carbazoles in a single operation. The "aromatic metamorphosis" of dibenzothiophenes into carbazoles does not require any heavy metals. This strategy is also applicable to the synthesis of indoles. Since electron-deficient thiaarene dioxides exhibit interesting reactivity, which is not observed for that the corresponding electron-rich azaarenes, a combination of a thiaarene-dioxide-specific reaction with the SN Ar-based aromatic metamorphosis allows transition-metal-free construction of difficult-to-prepare carbazoles
Unconventional Magnetic and Resistive Hysteresis in an Iodine-Bonded Molecular Conductor.

Article first published online: 14 JUL 2015Simultaneous manipulation of both spin and charge is a crucial issue in magnetic conductors. We report on a strong correlation between magnetism and conductivity in the iodine-bonded molecular conductor (DIETSe)2 FeBr2 Cl2 [DIETSe=diiodo(ethylenedithio)tetraselenafulvalene], which is the first molecular conductor showing a large hysteresis in both magnetic moment and magnetoresistance associated with a spin-flop transition. Utilizing a mixed-anion approach and iodine bonding interactions, we tailored a molecular conductor with random exchange interactions exhibiting unforeseen physical properties
Single-Molecule Visualization of the Activity of a Zn(2+) -Dependent DNAzyme.

We demonstrate the single-molecule imaging of the catalytic reaction of a Zn(2+) -dependent DNAzyme in a DNA origami nanostructure. The single-molecule catalytic activity of the DNAzyme was examined in the designed nanostructure, a DNA frame. The DNAzyme and a substrate strand attached to two supported dsDNA molecules were assembled in the DNA frame in two different configurations. The reaction was monitored by observing the configurational changes of the incorporated DNA strands in the DNA frame. This configurational changes were clearly observed in accordance with the progress of the reaction. The separation processes of the dsDNA molecules, as induced by the cleavage by the DNAzyme, were directly visualized by high-speed atomic force microscopy (AFM). This nanostructure-based AFM imaging technique is suitable for the monitoring of various chemical and biochemical catalytic reactions at the single-molecule level
Final-Stage Site-Selective Acylation for the Total Syntheses of Multifidosides A-C.

Article first published online: 28 AUG 2015The first total syntheses of multifidosides A-C have been achieved. The synthetic strategy is characterized by catalytic site-selective acylation of unprotected glycoside precursors in the final stage of the synthesis. High functional-group tolerance of the site-selective acylation, promoted by an organocatalyst, enabled the conventionally difficult molecular transformation in a predictable and reliable manner. An advantage of this strategy is to avoid the risks of undesired side reactions during the removal of the protecting groups at the final stage of the total synthesis
Ruthenium-catalyzed O- to S-alkyl migration:a pseudoreversible Barton-McCombie pathway

A practical ruthenium-catalyzed O- to S-alkyl migration affords structurally diverse thiooxazolidinones in excellent yields. Our studies suggest this catalytic transformation proceeds through a pseudoreversible radical pathway drawing mechanistic parallels to the classic Barton-McCombie reaction. A radical step in a new direction: A practical ruthenium-catalyzed O- to S-alkyl migration affords structurally diverse thiooxazolidinones in excellent yields. Experimental and computational studies suggest a pseudoreversible radical pathway drawing mechanistic parallels to the classic Barton-McCombie reaction
Nanowire Chemical/Biological Sensors: Status and a Roadmap for the Future

Chemiresistive sensors are becoming increasingly important as they offer an inexpensive option to conventional analytical instrumentation, they can be readily integrated into electronic devices, and they have low power requirements. Nanowires (NWs) are a major theme in chemosensor development. High surface area, interwire junctions, and restricted conduction pathways give intrinsically high sensitivity and new mechanisms to transduce the binding or action of analytes. This Review details the status of NW chemosensors with selected examples from the literature. We begin by proposing a principle for understanding electrical transport and transduction mechanisms in NW sensors. Next, we offer the reader a review of device performance parameters. Then, we consider the different NW types followed by a summary of NW assembly and different device platform architectures. Subsequently, we discuss NW functionalization strategies. Finally, we propose future developments in NW sensing to address selectivity, sensor drift, sensitivity, response analysis, and emerging applications
Pushing the limits of neutral organic electron donors : A tetra(iminophosphorano)-substituted bispyridinylidene

A new ground-state organic electron donor has been prepared that features four strongly π-donating iminophosphorano substituents on a bispyridinylidene skeleton. Cyclic voltammetry reveals a record redox potential of −1.70 V vs. saturated calomel electrode (SCE) for the couple involving the neutral organic donor and its dication. This highly reducing organic compound can be isolated (44 %) or more conveniently generated in situ by a deprotonation reaction involving its readily prepared pyridinium ion precursor. This donor is able to reduce a variety of aryl halides, and, owing to its redox potential, was found to be the first organic donor to be effective in the thermally induced reductive S[BOND]N bond cleavage of N,N-dialkylsulfonamides, and reductive hydrodecyanation of malonitriles
Thermosensitive Ion Channel Activation in Single Neuronal Cells by Using Surface-Engineered Plasmonic Nanoparticles.

光を使って神経細胞の「痛み」感知を制御する手法を開発 -新しい鎮痛療法の可能性-. 京都大学プレスリリース. 2015-08-14.Controlling cell functions using external photoresponsive nanomaterials has enormous potential for the development of cell-engineering technologies and intractable disease therapies, but the former currently requires genetic modification of the target cells. We present a method using plasma-membrane-targeted gold nanorods (pm-AuNRs) prepared with a cationic protein/lipid complex to activate a thermosensitive cation channel, TRPV1, in intact neuronal cells. Highly localized photothermal heat generation mediated by the pm-AuNRs induced Ca(2+) influx solely by TRPV1 activation. In contrast, the use of previously reported cationic AuNRs that are coated with a conventional synthetic polymer also led to photoinduced Ca(2+) influx, but this influx resulted from membrane damage. Our method provides an optogenetic platform without the need for prior genetic engineering of the target cells and might be useful for novel TRPV1-targeted phototherapeutic approaches
Zinc-catalyzed dual C–X and C–H borylation of aryl halides.

A zinc-catalyzed combined C[BOND]X and C[BOND]H borylation of aryl halides using B2pin2 (pin=OCMe2CMe2O) to produce the corresponding 1,2-diborylarenes under mild conditions was developed. Catalytic C[BOND]H bond activation occurs ortho to the halide groups if such a site is available or meta to the halide if the ortho position is already substituted. This method thus represents a novel use of a group XII catalyst for C[BOND]H borylation. This transformation does not proceed via a free aryne intermediate, but a radical process seems to be involved
Turning cucurbit[8]uril into a supramolecular nanoreactor for asymmetric catalysis

Chiral macromolecules have been widely used as synthetic pockets to mimic natural enzymes and promote asymmetric reactions. An achiral host, cucurbit[8]uril (CB[8]), was used for an asymmetric Lewis acid catalyzed Diels–Alder reaction. We achieved a remarkable increase in enantioselectivity and a large rate acceleration in the presence of the nanoreactor by using an amino acid as the chiral source. Mechanistic and computational studies revealed that both the amino acid–Cu2+ complex and the dienophile substrate are included inside the macrocyclic host cavity, suggesting that contiguity and conformational constraints are fundamental to the catalytic process and rate enhancement. These results pave the way towards new studies on asymmetric reactions catalyzed in confined achiral cavities.This research was supported by the European Union (European Research Council Starting GrantsASPiRe 240629 (OAS) and NUCLEOPOLY240080 (AH) and STREP project MICREAGENTS), the Netherlands Organization for Scientific Research (NWO-Vici Grant) and the Zernike Institute for Advanced Materials. E R. acknowledges computational support from the NIH Biowulf cluster, the EPSRC UK NSCCS cluster, and the ARCHER UK National Supercomputing Service via CCPBioSim.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/anie.20150562
A Tri-Phase Sorting System: Coordination Cages in Ionic Liquids

Host-guest chemistry is usually carried out in either water or organic solvents. To investigate the utility of alternative solvents, three different coordination cages were dissolved in neat ionic liquids. By using ¹⁹F NMR to observe the presence of free and bound guest molecules, all three cages were demonstrated to be stable and capable of encapsulating guests in ionic solution. Different cages were found to preferentially dissolve in different phases, allowing for the design of a tri-phase sorting system. Within this system, three coordination cages, Fe₄L₆ 2, Fe₈L₁₂ 3, and Fe₄L₄ 4, each segregated into a distinct layer. Upon the addition of a mixture of three different guests, each cage (in each separate layer) selectively bound its preferred guest.This work was supported by the European Research Council (259352). We also thank the Cambridge Chemistry NMR service for experimental assistance.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150577
Radical formation in the gas-phase ozonolysis of deprotonated cysteine

Although the deleterious effects of ozone on the human respiratory system are well-known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys-H]- are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free-radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis. Gas-phase reactions: Deprotonated cysteine reacted with ozone to give a rich set of products including sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfonate, and sulfonate anions, and significantly sulfenate radical anions formed by ejection of a hydroperoxy radical (see picture). The free-radical pathway occurred only when both thiol and carboxylate moieties were available
Photoelectron spectroscopy at the graphene-liquid interface reveals the electronic structure of an electrodeposited cobalt/graphene electrocatalyst

Electrochemically grown cobalt on graphene exhibits exceptional performance as a catalyst for oxygen evolution reactions and provides the possibility of controlling the morphology and the chemical properties during deposition. However, the detailed atomic structure of this hybrid material is not well understood. To elucidate the Co/graphene electronic structure we have developed a flow cell closed by a graphene membrane that provides electronic and chemical information of active surfaces under atmospheric pressure and in the presence of liquids by means of X-ray photoelectron spectroscopy (XPS). We found that cobalt anchors on graphene via carbonyl-like species, i.e. Co(CO)_x promoting the reduction of Co^3+ to Co^2+, which is believed to be the active site of the catalyst.HZB is acknowledged for granting beamtime at the ISSIS endstation under proposal #14201159. This work was funded from EU project GRAFOL grant 285275 and by SYNESTESia project grant 05K14EWA (BMBF). R.S.W. acknowledges a Research Fellowship from St. John’s College, Cambridge and a Marie Skłodowska-Curie Individual Fellowship (Global) under grant ARTIST (no. 656870) from the European Union’s Horizon 2020 research and innovation programme.. C.H.C. acknowledges financial support from projects 103-2112-M-032-004 and 102-2632-M-032-001 -MY3. M.S. was supported by the Office of Science, Division of Materials Sciences and Engineering, of the U.S. Department of Energy (DOE) under Contract No. DEAC02-05CH11231.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150604
Photocatalytic Formic Acid Conversion on CdS Nanocrystals with Controllable Selectivity for H_2 or CO

Formic acid is considered a promising energy carrier and hydrogen storage material for a carbon-neutral economy. We present an inexpensive system for the selective room temperature photocatalytic conversion of formic acid to either hydrogen or carbon monoxide. Under visible-light irradiation (λ>420 nm, 1 sun), suspensions of ligand-capped cadmium sulfide nanocrystals in formic acid/sodium formate release up to 116 ±14 mmol H_2 g_cat^−1 h^−1 with >99% selectivity when combined with a cobalt co-catalyst; the quantum yield at λ=460 nm was 21.5±2.7%. In the absence of capping ligands, suspensions of the same photocatalyst in aqueous sodium formate generate up to 102±13 mmol CO g_cat^−1 h^−1 with >95% selectivity and 19.7±2.7% quantum yield. H_2 and CO production was sustained for more than one week with turnover numbers greater than 6·10^5 and 3·10^6, respectively.This work was supported by the Christian Doppler Research Association (Austrian Federal Ministry of Science, Research and Economy and the National Foundation for Research, Technology and Development), the OMV Group, the EPSRC (EP/H00338X/2 to ER), the Isaac Newton Trust, the German Research Foundation (MFK), and the Advanced Institute for Materials Research-Cambridge Joint Research Centre (KLO). XPS spectra were obtained at the National EPSRC XPS User's Service (NEXUS) at Newcastle University, an EPSRC Mid-Range Facility.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150623
Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML
Global and Local Conformation of Human IgG Antibody Variants Rationalises Loss of Thermodynamic Stability

Immunoglobulin G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150722
Three aromatic residues are required for electron transfer during iron mineralization in bacterioferritin

© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Ferritins are iron storage proteins that overcome the problems of toxicity and poor bioavailability of iron by catalyzing iron oxidation and mineralization through the activity of a diiron ferroxidase site. Unlike in other ferritins, the oxidized di-Fe3+ site of Escherichia coli bacterioferritin (EcBFR) is stable and therefore does not function as a conduit for the transfer of Fe3+ into the storage cavity, but instead acts as a true catalytic cofactor that cycles its oxidation state while driving Fe2+ oxidation in the cavity. Herein, we demonstrate that EcBFR mineralization depends on three aromatic residues near the diiron site, Tyr25, Tyr58, and Trp133, and that a transient radical is formed on Tyr25. The data indicate that the aromatic residues, together with a previously identified inner surface iron site, promote mineralization by ensuring the simultaneous delivery of two electrons, derived from Fe2+ oxidation in the BFR cavity, to the di-ferric catalytic site for safe reduction of O2. A radical view of bacterioferritin: Three aromatic residues located close to the catalytic ferroxidase site are shown to be important for iron mineralization. A transient radical is associated with Tyr25, consistent with a mechanism where electrons from Fe2+ oxidation are transferred to the oxidized, di-Fe3+ ferroxidase site, ensuring that two electrons arrive at the site simultaneously and avoid formation of toxic reactive oxygen species
Alkali-metal-mediated magnesiations of an N-heterocyclic carbene : normal, abnormal and "paranormal" reactivity in a single tritopic molecule

Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6-tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N-heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr2-. Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr- monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali-metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC
Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics

Antibodies are currently the fastest-growing class of therapeutics. Although naked antibodies have proven valuable as pharmaceutical agents, they have some limitations, such as low tissue penetration and a long circulatory half-life. They have been conjugated to toxic payloads, PEGs, or radioisotopes to increase and optimize their therapeutic efficacy. Although nonspecific conjugation is suitable for most in vitro applications, it has become evident that site specifically modified antibodies may have advantages for in vivo applications. Herein we describe a novel approach in which the antibody fragment is tagged with two handles: one for the introduction of a fluorophore or F isotope, and the second for further modification of the fragment with a PEG moiety or a second antibody fragment to tune its circulatory half-life or its avidity. Such constructs, which recognize Class II MHC products and CD11b, showed high avidity and specificity. They were used to image cancers and could detect small tumors.Cancer Research Institute (New York, N.Y.)United States. National Institutes of Health (R01-AI087879-06)United States. National Institutes of Health (DP1-GM106409-03)United States. National Institutes of Health (R01-GM100518-04
Intramolecular Fluorocyclizations of Unsaturated Carboxylic Acids with a Stable Hypervalent Fluoroiodane Reagent

The file associated with this record is under a 12-month embargo from publication in accordance with the publisher Copyright transfer agreement, available at http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291521-3773/homepage/2002_authors.html. The full text may be available through the publisher links provided above.A new class of fluorinated lactones was prepared by the intramolecular fluorocyclizations of unsaturated carboxylic acids by using the stable fluoroiodane reagent in combination with AgBF4 . This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step. The fluoroiodane reagent, prepared easily from fluoride, can also be used without a metal catalyst to give moderate yields within just 1 hour, thus demonstrating that it is a suitable reagent for developing new (18) F-labelled radiotracers for PET imaging.Peer-reviewedPost-prin