Alteration of the Conformational Dynamics of a DNA Hairpin by α-Synuclein in the Presence of Aqueous Two-Phase Systems

The effect of an amyloidogenic intrinsically disordered protein, α-synuclein, which is associated with Parkinson's disease (PD), on the conformational dynamics of a DNA hairpin (DNA-HP) was studied by employing the single-molecule Förster resonance energy transfer method. The open-to-closed conformational equilibrium of the DNA-HP is drastically affected by binding of monomeric α-synuclein to the loop region of the DNA-HP. Formation of a protein-bound intermediate conformation is fostered in the presence of an aqueous two-phase system mimicking intracellular liquid-liquid phase separation. Using pressure modulation, additional mechanistic information about the binding complex could be retrieved. Hence, in addition to toxic amyloid formation, α-synuclein may alter expression profiles of disease-modifying genes in PD. Furthermore, these findings might also have significant bearings on the understanding of the physiology of organisms thriving at high pressures in the deep sea.     

Mimicking the Biologically Active Part of the Cyclopeptides Segetalin A and B by “Clipping” of a Linear Tripeptide Derivative by Metal Coordination

A new method for the conformational fixation of bioactive loop-type peptide structures is presented. Hereby, ligand moieties are attached to the termini of a linear peptide sequence. Upon metal complexation, a macrocyclic structure with a loop-type conformation of the peptide is formed. As a representative example, the preparation of a WAG-bridged dicatechol derivative is described which mimics the active part of the natural products Segetalin A and Segetalin B.     

Construction of Stable Helical Metal-Organic Frameworks with a Conformationally Rigid “Concave Ligand”

A helical metal-organic framework was prepared by using a conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups were applied to introduce atropic repulsion, thereby allowing the formation of extended frameworks for the first time. With this new ligand design, a helical-shaped MOF with significantly improved air and moisture stability was successfully prepared, thus providing a new strategy for ligand design toward porous material constructions.     

Easy Production of “Difficult Peptides” Using Cell-Free Protein Synthesis and a New Methionine Analogue as a Latent Peptide Cleavage Site

Aliphatic γ-chloro-α-amino acids incorporated in place of their canonical analogues through cell-free protein synthesis act as heat-labile linkers, offering a useful strategy for the straightforward production of target peptides as fusion proteins, from which the targets are readily released. Until now, the natural abundance of aliphatic amino acids in peptides has limited the scope of the method, as it leads to undesired cleavage sites in synthesized products, but here the authors report the development of a new cleavable chloro amino acid that incorporates in place of the relatively rare amino acid methionine, thus greatly expanding the scope of producible targets. This new strategy is employed for simplified peptide synthesis with a methionine-free fusion partner, allowing single-site incorporation of the cleavable linker for clean release and easy purification of the target peptide. Its utility is demonstrated through the straightforward preparation of two peptides reported to be challenging targets and not accessible through standard solid-phase chemical methodologies, as well as analogues.     

The effect of silica–alumina catalysts on degradation of polyolefins by a continuous flow reactor

Catalytic degradation of polyolefins was performed in a continuous flow reactor that allows the study of the degradation processes at steady state, characterized by constant values of reaction parameters and properties of the products. The continuous flow reactor was operated at atmospheric pressure and at feed rate of 0–1.5 kg h^?1 polyolefins over two silica–alumina catalysts having different SiO₂/Al₂O₃ mole ratio. Polyethylene (PE), polypropylene (PP) and polystyrene (PS) were degraded at 420, 380 and 360 °C respectively. The cracking effect of silica–alumina was proved by the increased amount of gaseous products and by the decreased molecular weight of liquid products. The differences in surface area and in concentration and acidic strength of active centers of the two catalysts affected the distribution of degradation products. Molar rate of degradation was increased in the presence of catalysts, however the mass rate of degradation was decreased leading to higher values of the calculated activation energies. These interesting results might open new perspectives in understanding the macroscopic mechanism for catalytic degradation of polyolefins.     

The Epimerization of 10-Deacetylbaccatin Ⅲ by Microsphaeropsis Onychiuri a Fungus from Taxus Yunnanensis

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Electrode grafting by oxidation of an amine catalyzed by a ferrocenyl “antenna” through intramolecular electron transfer

Two aminoferrocene complexes were studied by electrochemical techniques. Molecules retain the redox properties of both ferrocene and amine groups, but fundamentally different behaviours were observed depending on whether the linker between the two redox end groups was saturated (ethyl bridge) or not (ethynyl bridge). The possibility of an intramolecular electron transfer from the amine to the ferricenium moiety through the π-conjugated linker was demonstrated and the ethynyl bridge is expected to have a dual effect by facilitating both the oxidation of the amine into the cation radical and the production of aminyl radical, due to its strong electron withdrawing effect. Because of this synergy of properties, grafting of the conjugated aminoferrocene complex can occur just by oxidizing the ferrocene group without the presence of a base in solution.     

The “off-template” problem: synthesis and alkylation of a fused-butyrolactone from d-glucose

The synthesis of a fused-butyrolactone from D-glucose and its stereospecific alkylation in an off-template position is described, together with an unusual silyl protecting group migration.     

The development of a versatile field program for measuring tritium in “real-time”

Robust sample handling and liquid scintillation counting (LSC) procedures have been developed to routinely monitor tritium in the field relative to the 20,000 pCi/L drinking water standard. This procedure allows tritium to be monitored hourly during 24 hour drilling operations at depths in the saturated zone potentially contaminated by sub-surface nuclear weapons testing at the Nevada Test Site. Using retrofitted, shock hardened, vibration damped counters and strict analytical protocols, tritium may be measured rapidly in the field under hostile conditions. Concentration standards and dead tritium backgrounds are prepared weekly in a central laboratory and delivered to remote drilling locations where they are recounted daily as a check on counter efficiency and calibration. Portable LSC counters are located in trailers and powered off a battery pack and line filter fed by mobile generator. The samples are typically groundwaters mixed with drilling fluids returned after circulation through a drill string. Fluids are aerated and de-foamed, filtered, mixed with scintillation cocktail and dark adapted before counting. Real-time monitoring affords drilling and field personnel early warning against intercepting down-gradient plumes of radioactivity. For routine operations, the tritium activity may not exceed a 10,000 pCi/L threshold.     

Synthesis of Star-like Polybutadienes by a Combination of Living Anionic Polymerization and “Click” Coupling Method

Three-arm and four-arm star-like polybutadienes(PBds) were synthesized via the combination of living anionic polymerization and the click coupling method. Kinetic study showed that the click reaction between the azido group terminated PBd-t-N3 and the alkyne-containing multifunctional linking reagent was fast and highly efficient. All coupling reactions were fully accomplished within 40 min at 50 °C in toluene in the presence of the reducing agent Cu(0), proven by 1H-NMR, FTIR and GPC measurements. For the coupling reactions between the PBd-t-N3 polymer and dialkyne-containing compound, the final conversion of the coupled PBd-PBd polymer was ca. 97.0%. When a PBd-t-N3 polymer was reacted with trialkyne-containing or tetraalkyne-containing compound, the conversion of three-arm or four-arm PBd was around 95.5% or 87.0%, respectively. Several factors influencing the coupling efficiency were studied, including the molecular weight of the initial PBd-t-N3, arm numbers and the molar ratio of the azido group to the alkynyl group. The results indicated that the conversion of the target products would be promoted when the molecular weight of the PBd-t-N3 was low and the molar ratio of the azido to alkynyl groups was close to 1.     

The “On Line” Determination of Cefsulodin by High Performance Liquid Chromatography in CSF and Plasma of Rats

Abstract

After an intraveinous injection of 20 mg.kg^?1 of cefsulodin in anaesthetized rats, the cerebrospinal fluid (CSF) and plasma drug levels were determined on line by HPLC. The CSF was withdrawn from the IIIe venticle at a flow rate of I μl. minute and pushed with a peristaltic pump, via a teflon tube into a “micro vial” inside the WISP vial. At the end of fiveteen minutes, about 15 μ1 of CSF was collected and a small volume (7 μl) was injected by the WISP into the column, the excess of CSF was discarded by another teflon tube inside the “micro-vial”. After the injection, the continous flow of CSF filled the “micro vial”, an injection was running at fiveteen minutes and so on during three hours. Plasma samples were collected every thirty minutes, and after methanol extraction cefsulodin levels were determined by HPLC. Given the low drug levels found in the CSF, this method appeared very sensitive; it was a direct, rapid, automatic technique. Other biological molecules can be determined by this automatic dosage.     

The “Inverted Bonds” Revisited: Analysis of “In Silico” Models and of [1.1.1]Propellane by Using Orbital Forces

This article dwells on the nature of “inverted bonds”, which refer to the σ interaction between two sp hybrids by their smaller lobes, and their presence in [1.1.1]propellane. Firstly, we study H₃C−C models of C−C bonds with frozen H-C-C angles reproducing the constraints of various degrees of “inversion”. Secondly, the molecular orbital (MO) properties of [1.1.1]propellane and [1.1.1]bicyclopentane are analyzed with the help of orbital forces as a criterion of bonding/antibonding character and as a basis to evaluate bond energies. Triplet and cationic states of [1.1.1]propellane species are also considered to confirm the bonding/antibonding character of MOs in the parent molecule. These approaches show an essentially non-bonding character of the σ central C−C interaction in propellane. Within the MO theory, this bonding is thus only due to π-type MOs (also called “banana” MOs or “bridge” MOs) and its total energy is evaluated to approximately 50 kcal mol⁻¹. In bicyclopentane, despite a strong σ-type repulsion, a weak bonding (15–20 kcal mol⁻¹) exists between both central C−C bonds, also due to π-type interactions, though no bond is present in the Lewis structure. Overall, the so-called “inverted” bond, as resulting from a σ overlap of the two sp hybrids by their smaller lobes, appears highly questionable.     

Simultaneous Determination of Ten Active Components in Chinese Medicine “Huang-Lian-Shang-Qing” Tablets by High-Performance Liquid Chromatography Coupled with Photodiode Array Detection

A simple and sensitive high-performance liquid chromatography coupled with a photodiode array detection (HPLC-PAD) method was investigated for the simultaneous determination of ten components (rutin, berberine, palmatine, baicalin, wogonoside, baicalein, wogonin, emodin, chrysophanol, and physcion) in “Huang-Lian-Shang-Qing” (HLSQ) tablets. The method was optimized and the mobile phase composed of methanol (A)-3% phosphoric acid (B) was used to elute the targets in a gradient elution mode. All the calibration curves, precisions, and recoveries were good. Then, this method was successfully used to determine the ten compounds in 33 batches of HLSQ tablets for quality control of this medicinal product.     

“Agricultural Chymistry is at present in it's infancy”: The Board of Agriculture,The Royal Institution and Humphry Davy

In this paper I sketch the institutional interactions between the Board of Agriculture and the Royal Institution in the late eighteenth and early nineteenth centuries. This includes analysing the composition of memberships and committees of both bodies in which, inter alia, I challenge Morris Berman's account of their institutional relations. A key figure was Humphry Davy who, because of his career ambitions, occupied a slightly uncomfortable position as Professor of Chemistry to both organisations. Davy's lecture notebooks and his subsequent publication Elements of Agricultural Chemistry reveal that he drew almost all his direct knowledge of the subject from Britain and Ireland. Yet, despite such parochial shortcomings that might be expected of an infant science at time of war, the popularity of his book, particularly in North America, provided continuity between the end of the Board of Agriculture in 1822 and the start of the impact of Justus Liebig's work in the 1840s.     

π–π Stacking Interaction in an Oxidized CuII–Salen Complex with a Side-Chain Indole Ring: An Approach to the Function of the Tryptophan in the Active Site of Galactose Oxidase

In order to gain new insights into the effect of the π–π stacking interaction of the indole ring with the Cu^II–phenoxyl radical as seen in the active form of galactose oxidase, we have prepared a Cu^II complex of a methoxy-substituted salen-type ligand, containing a pendent indole ring on the dinitrogen chelate backbone, and characterized its one-electron-oxidized forms. The X-ray crystal structures of the oxidized Cu^II complex exhibited the π–π stacking interaction of the indole ring mainly with one of the two phenolate moieties. The phenolate moiety in close contact with the indole moiety showed the characteristic phenoxyl radical structural features, indicating that the indole ring favors the π–π stacking interaction with the phenoxyl radical. The UV/Vis/NIR spectra of the oxidized Cu^II complex with the pendent indole ring was significantly different from those of the complex without the side-chain indole ring, and the absorption and CD spectra exhibited a solvent dependence, which is in line with the phenoxyl radical–indole stacking interaction in solution. The other physicochemical results and theoretical calculations strongly support that the indole ring, as an electron donor, stabilizes the phenoxyl radical by the π–π stacking interaction.