Identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening

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Highlights? Development of an assay for LF protease using a full-length protein substrate ? Lichen depsidones identified as exosite-targeting LF inhibitors ? Exosite inhibitors protect macrophages from LF cytotoxicity     

Update of spectroscopic data for 4-hydroxydictyolactone and dictyol E isolated from a Halimeda stuposa - Dictyota sp. assemblage

The methanol extract of an assemblage of Halimeda stuposa and a Dictyota sp., yielded three natural products characteristic of Dictyota sp., and one of Halimeda sp. These included the xenicane diterpene 4-hydroxydictyolactone (1), and the diterpenes dictyol E (2), 8a,11-dihydroxypachydictyol A (3) and indole-3-carboxaldehyde (4). A minor revision of 1 and new spectroscopic data for 1 and 2 are provided, along with associated anti-cancer activities of compounds.     

A first-principles study of ultrathin nanofilms of MgO-supported TiN

As a first step towards a microscopic understanding of supported ultrathin nanofilms of TiN, we present state-of-the-art density-functional theory (DFT) calculations to investigate the interfacial properties of the TiN/MgO system as a function of film thickness. Optimized atomic geometries, energetics, and analysis of the electronic structure of the TiN/MgO systems are reported. In particular, we find that the work function of 1 ML of TiN(100) on MgO(100) exhibits a significant decrease, rationalized by the large surface dipole moment formation due to the changes in charge densities at the interface of this system. This decrease in the work function of TiN/MgO systems (as compared to pristine MgO(100) surface) could well benefit their application in metal-oxide-semiconductor devices as an ideal gate-stack material.     

Tandem Payne/Meinwald versus Meinwald rearrangements on the α-hydroxy- or α-silyloxy-spiro epoxide skeleton

Under Lewis acid activation, the new α-hydroxy-spiro epoxide scaffold 1a underwent an original tandem Payne/Meinwald rearrangement affording the cyclopentyl hydroxymethylketone 6 in a stereospecific manner, while a Meinwald-type epoxide rearrangement occurred when the derived α-trimethylsilyloxy-spiro epoxide 2a was treated with MABR, yielding stereoselectively the cyclohexane carbaldehyde 9.     

Temporary thio-derivatization in the synthesis of (+)-4-acetylbromoxone

A stereocontrolled synthesis of the marine natural products (+)-bromoxone (1) and (+)-4-acetylbromoxone (2) is reported. The sequence features the enzymatic kinetic resolution of 4-hydroxycyclohexenone (6) via its S-benzyl adduct. Thereafter, a base-mediated elimination-silylation generated an optically active (−)-4S-4-tert-butyldimethylsilyoxycyclohexenone (5), which then underwent diastereoselective epoxidation. Saegusa-Ito oxidation enabled formation of the corresponding α,β-unsaturated ketone 13. Bromination-elimination and subsequent removal of the silicon protecting group afforded (+)-bromoxone (1) which was converted into (+)-(4S,5R,6R)-4-acetoxy-2-bromo-5,6-epoxycyclohex-2-enone (2) [(+)-4-acetylbromoxone]. Using a luciferase gene reporter assay ED₅₀ for NFκB inhibition of 9 μM was determined.     

Metal Coordination Induced π-Extension and Triplet State Production in Diketopyrrolopyrrole Chromophores

Triplet state photophysics has been generated in two distinct diketopyrrolopyrrole (DPP) chromophores terminated with either phenyl (1) or thienyl (2) spacers, when sandwiched between two Ir(III) complexes using bipyridyl linkers. Upon coordination of the bpy-DPP-bpy subunit resulting in its planarization, the π-conjugation in the DPP chromophore formally extends and was manifested as a substantial red shift in the absorption and fluorescence profiles of 1 and 2. Low energy excitation of these dinuclear metal complexes produced strongly quenched singlet fluorescence, generated quite intense long-lived (τ ～ 3 μs) absorption transients in the red, sensitized (1)O(2) photoluminescence centered at 1270 nm in aerated solutions, and yielded low temperature near-IR phosphorescence in 1 centered at 950 nm.     

Ligand-Localized Triplet-State Photophysics in a Platinum(II) Terpyridyl Perylenediimideacetylide

The synthesis, electrochemistry, and photophysical behavior of a Pt(II) terpyridyl perylenediimide (PDI) acetylide (1) charge-transfer complex is reported. The title compound exhibits strong (ε ≈ 5 × 10(4) M(-1)cm(-1)) low-energy PDI acetylide-based π-π* absorption bands in the visible range extending to 600 nm, producing highly quenched singlet fluorescence (Φ = 0.014 ± 0.001, τ = 109 ps) with respect to a nonmetalated PDI model chromophore. Nanosecond transient absorption spectroscopy revealed the presence of a long excited-state lifetime (372 ns in 2-methyltetrahydrofuran) with transient features consistent with the PDI-acetylide triplet state, ascertained by direct comparison to a model Pt(II) PDI-acetylide complex lacking low-energy charge-transfer transitions. For the first time, time-resolved step-scan FT-IR spectroscopy was used to characterize the triplet excited state of the PDI-acetylide sensitized in the title compound and its associated model complex. The observed red shifts (～30-50 cm(-1)) in the C═O and C≡C vibrations of the two Pt(II) complexes in the long-lived excited state are consistent with formation of the (3)PDI acetylide state and found to be in excellent agreement with the expected change in the relevant DFT-calculated IR frequencies in the nonmetalated PDI model chromophore (ground singlet state and lowest triplet excited state). Formation of the PDI triplet excited state in the title chromophore was also supported by sensitization of the singlet oxygen photoluminescence centered at ～1275 nm in air-saturated acetonitrile solution, Φ((1)O(2)) = 0.52. In terms of light emission, only residual PDI-based red fluorescence could be detected and no corresponding PDI-based phosphorescence was observed in the visible or NIR region at 298 or 77 K in the Pt(II) terpyridyl perylenediimideacetylide.     

Palladium-catalyzed Ullmann-type reductive homocoupling of iodoaryl glycosides

A catalytic synthesis of novel biaryl-linked divalent glycosides was achieved using an electroreductive palladium-catalyzed iodoaryl-iodoaryl coupling reaction. This new method was optimized for the synthesis of divalent biaryl-linked mannopyranosides that was subsequently generalized toward several carbohydrate substrates with yields up to 96%.