Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.

Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from : this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps.

Light-Enabled Enantiodivergence: Stereospecific Reduction of Activated Alkenes Using a Single Organocatalyst Enantiomer.

Light-enabled enantiodivergence is demonstrated in which the alkene substrate configuration is manipulated ( → ) prior to organocatalytic reduction with a chiral thiourea and Hantzsch ester. This allows stereodivergent reduction to be regulated at the substrate level with high fidelity and mitigates the need for a second, enantiomeric catalyst (up to 93:07 and 95:5 ). The synthetic utility of this strategy has been demonstrated in the synthesis of the weight-loss drug ()-Lorcaserin (Belviq) and a potent AMPA modulator.

Inverting External Asymmetric Induction via Selective Energy Transfer Catalysis: A Strategy to β-Chiral Phosphonate Antipodes.

Enantiodivergent, catalytic reduction of activated alkenes relays stereochemical information encoded in the antipodal chiral catalysts to the pro-chiral substrate. Although powerful, the strategy remains vulnerable to costs and availability of sourcing both catalyst enantiomers. Herein, a stereodivergent hydrogenation of α,β-unsaturated phosphonates is disclosed using a single enantiomer of the catalyst.

Fluorinated Analogues of the Histone Deacetylase Inhibitor Vorinostat (Zolinza): Validation of a Chiral Hybrid Bioisostere, BITE.

A chiral, hybrid bioisostere of the CF and Et groups (BITE) was installed in a series of vorinostat (Zolinza) analogues, and their histone deacetylase (HDAC) inhibitory behavior was studied relative to that of their nonfluorinated counterparts. Several of these compounds containing the 1,2-difluoroethylene unit showed potency greater than that of the clinically approved drug itself against HDAC1. This trend was found to be general with the BITE-modified HDAC inhibitors performing significantly better than the ethyl derivatives.

Stereocontrolled Synthesis of Tetrafluoropentanols: Multivicinal Fluorinated Alkane Units for Drug Discovery.

A stereodivergent synthesis of four diastereomeric 2,3,4,5-tetrafluoropentanols is disclosed. X-ray crystallographic analysis reveals conformations that manifest sequential stereoelectronic effects (σ → σ*), thereby generating topological diversity via subtle C(sp)-H to C(sp)-F exchange. Two representative tetrafluoro arrays have been incorporated into truncated analogues of Gilenya for the management of relapsing remitting multiple sclerosis.

DNA Methylation Patterns in the Round Goby Hypothalamus Support an On-The-Spot Decision Scenario for Territorial Behavior.

The question as to how early life experiences are stored on a molecular level and affect traits later in life is highly topical in ecology, medicine, and epigenetics. In this study, we use a fish model to investigate whether DNA methylation mediates early life experiences and predetermines a territorial male reproductive phenotype In fish, adult reproductive phenotypes frequently depend on previous life experiences and are often associated with distinct morphological traits. DNA methylation is an epigenetic mechanism which is both sensitive to environmental conditions and stably inherited across cell divisions.

Magnetoelastic Effects in Doubly Clamped Electroplated CoFe Microbeam Resonators.

Magnetostrictive CoFe films are fully suspended to produce free-standing, clamped-clamped, microbeam resonators. A negative or positive shift in the resonant frequency is observed for magnetic fields applied parallel or perpendicular to the length of the beam, respectively, confirming the magnetoelastic nature of the shift. Notably, the resonance shifts linearly with higher-bias fields oriented perpendicular to the beam's length.

Effect of CoFe dusting layer and annealing on the magnetic properties of sputtered Ta/W/CoFeB/CoFe/MgO layer structures.

We explored the effect of a CoFe wedge inserted as a dusting layer (0.2 nm-0.4 nm thick) at the CoFeB/MgO interface of a sputtered Ta(2 nm)/W(3 nm)/CoFeB(0.

The high-intensity reflectometer of the Jülich Centre for Neutron Science: MARIA.

MARIA (magnetism reflectometer with high incident angle) is a world class vertical sample reflectometer dedicated to the investigation of thin films in the fields of magnetism, soft matter and biology. The elliptical vertically focusing guide allows one to measure small samples with a typical size of 1 × 1 cm very efficiently. The double-bounce polarizer and the pumped He SEOP (spin-exchange optical pumping) neutron spin filter cell for analysing the polarization of the reflected neutron beam can be moved into the beam in seconds.

Transient Optical and Terahertz Spectroscopy of Nanoscale Films of RuO.

Solution-deposited nanoscale films of RuO ("nanoskins") are effective transparent conductors once calcined to 200 °C. Upon heating the nanoskins to higher temperature the nanoskins show increased transmission at 550 nm. Electronic microscopy and X-ray diffraction show that the changes in the optical spectrum are accompanied by the formation of rutile RuO nanoparticles.

Indirect synthesis of a pair of formal methane activation products at a phosphane/borane frustrated Lewis pair.

The regioisomeric formal MesPCHCHB(CF) FLP methane splitting products MesP(H)CHCHB(CH)(CF) and MesP(CH)CHCHB(H)(CF) were produced by indirect stepwise reactions. They were stable at 60 °C and were both characterized by X-ray diffraction. A DFT analysis revealed that their formation from the FLP and CH would be endergonic by +6.

Energy Transfer Sensitization of Luminescent Gold Nanoclusters: More than Just the Classical Förster Mechanism.

Luminescent gold nanocrystals (AuNCs) are a recently-developed material with potential optic, electronic and biological applications. They also demonstrate energy transfer (ET) acceptor/sensitization properties which have been ascribed to Förster resonance energy transfer (FRET) and, to a lesser extent, nanosurface energy transfer (NSET). Here, we investigate AuNC acceptor interactions with three structurally/functionally-distinct donor classes including organic dyes, metal chelates and semiconductor quantum dots (QDs).

Disordered RuO2 exhibits two dimensional, low-mobility transport and a metal-insulator transition.

The discovery of low-dimensional metallic systems such as high-mobility metal oxide field-effect transistors, the cuprate superconductors, and conducting oxide interfaces (e.g., LaAlO3/SrTiO3) has stimulated research into the nature of electronic transport in two-dimensional systems given that the seminal theory for transport in disordered metals predicts that the metallic state cannot exist in two dimensions (2D).

α-CH acidity of alkyl-B(CF) compounds - the role of stabilized borata-alkene formation in frustrated Lewis pair chemistry.

Alkyl-B(CF) boranes are markedly α-CH-acidic. Using DFT we have calculated the p -values of a series of examples. Typically, (CF)B-CH [p (calcd) = 18.

Polymorphism in P,P-[3]ferrocenophanes: insights from an NMR crystallographic approach.

Polymorphism phenomena in P,P-[3]ferrocenophanes were studied by (31)P and (13)C solid-state NMR spectroscopy and suitable DFT calculations. "No-bond" indirect (31)P(31)P spin-spin coupling constants serve as a rather sensitive tool for the characterization of such systems, particularly since this NMR observable strongly depends on intermolecular PP distances and mutual orientations of the phosphorus lone pairs. Indeed, the structure of a previously unknown pseudo-polymorphism of a P,P-[3]ferrocenophane was determined via the emerging tool kit of "NMR crystallography", where structural inputs and constraints determined by modern solid-state NMR techniques, aided by DFT calculations, are used for faster and more reliable structure solution or refinement of X-ray powder diffraction patterns.

Indirect "no-bond" ³¹P···³¹P spin-spin couplings in P,P-[3]ferrocenophanes: insights from solid-state NMR spectroscopy and DFT calculations.

No-bond (31)P-(31)P indirect dipolar couplings, which arise from the transmission of nuclear spin polarization through interaction of proximal nonbonded electron pairs have been investigated in the solid state for a series of closely related substituted P,P-[3]ferrocenophanes and model systems. Through variation and combination of ligands (phenyl, cyclohexyl, isopropyl) at the two phosphorus sites, the P···P distances in these compounds can be varied from 3.49 to 4.

Ethene/alkyne exchange reaction at an intramolecular frustrated Lewis pair.

A vicinal ethylene bridged S/B frustrated Lewis pair (FLP) in situ generated by a hydroboration reaction of phenyl vinyl sulfide, reacts with p-tert-butylphenylacetylene by ethene/alkyne exchange and subsequent 1,2-addition of a second alkyne equivalent to give a zwitterionic sulfonium/borate product.

Dibenzopentalenes from B(C6F5)3-induced cyclization reactions of 1,2-bis(phenylethynyl)benzenes.

'Lene' and mean: The strong Lewis acid B(C6F5)3 efficiently converts some bis(arylethynyl)benzenes into dibenzopentalenes through a series of Lewis acid induced cyclization reactions at room temperature. Thus the reaction has the potential to be useful in the synthesis of substituted dibenzopentalene derivatives which are difficult to make by conventional means.

A room-temperature semiconductor spaser operating near 1.5 μm.

Room temperature spasing of surface plasmon polaritons at 1.46 μm wavelength has been demonstrated by sandwiching a gold-film plasmonic waveguide between optically pumped InGaAs quantum-well gain media. The spaser exhibits gain narrowing, the expected transverse-magnetic polarization, and mirror feedback provided by cleaved facets in a 1-mm long cavity fabricated with a flip-chip approach.

An integrated surface-plasmon source.

A compact and versatile source of coherent surface-plasmon polaritions (SPPs) is demonstrated by end-coupling a laser diode operating at 1.46 microm to a plasmonic waveguide integrated on the same microchip. With an optimized overlap between the spatial-modes of the laser and a planar-stripe waveguide, a high coupling efficiency of approximately 36% is achieved, that computations show could approach approximately 60% with smaller, readily achievable gaps between laser and waveguide.

Magnetic properties of lanthanide chalcogenide semiconducting nanoparticles.

To understand the importance of the band gap to the magnetic ordering in magnetic semiconductors, we have studied the effect of particle size on the ferromagnetic Curie temperature in semiconducting EuS. We have synthesized capped approximately 20 nm EuS nanoparticles using a single-source precursor, [Eu(S(2)CN(i)()Bu(2))(3)Phen] decomposed in trioctylphosphine. The nanoparticles have been characterized by X-ray powder diffraction, TEM, and magnetic susceptibility measurements as a function of temperature and field.

Guided resonances in asymmetrical GaN photonic crystal slabs observed in the visible spectrum.

We demonstrate that guided resonant modes can be readily observed in asymmetrical photonic crystal slabs on high-index substrates. In spite of the high radiative loss associated with all optical modes in these cases, the guided resonant modes are found to give rise to strong high-Q features in the transmission spectra. Since these photonic crystal structures are far more robust and easier to fabricate than the free-standing photonic crystal membranes used in previous studies of guided resonant modes, detailed studies of relevant optical phenomena and the implementation of proposed applications are greatly simplified.