Selective Formation of Helical Tetrapyrrin-Fused Porphyrins by Oxidation of β-to-β Linked meso-Aminoporphyrin Dimers

Oxidation of β-to-β directly linked and sulfur-bridged meso-amino Ni^II-porphyrin dimers with PbO₂ gave helical tetrapyrrin (biliverdin analogue)-fused Ni^II-porphyrins. These ring cleaving reactions differ markedly from the previously reported oxidation of a β–β linked Ni^II-porphyrin dimer carrying one amino group, which gave an azepine-fused porphyrin dimer. The tetrapyrrin-fused Ni^II-porphyrins display intense NIR absorption bands at 1200–1400 nm and reversible redox processes because of the highly π-conjugated networks and rigid structures. These tetrapyrrin-fused Ni^II-porphyrins were separated to stable enantiomers, which showed clear Cotton effects in their CD spectra with Δϵ of 10² order.     

Inhibition of the Fibrillation of Amyloid Aβ1-40 by Hybrid-Lipid-Polymer Vesicles

The transformation of functional proteins into amyloidic plaques is responsible for the impairment of neurological functions in patients fallen victim to debilitating neurological conditions like Alzheimer's, Parkinson's, and Huntington's diseases. The nucleating role of amyloid beta (Aβ_1-40) peptide into amyloids is well established. Herein, lipid hybrid-vesicles are generated with glycerol/cholesterol-bearing polymers aiming to alter the nucleation process and modulate the early phases of Aβ_1-40 fibrillation. Hybrid-vesicles (±100 nm) are prepared by incorporating variable amounts of cholesterol-/glycerol-conjugated poly(di(ethylene glycol)_macrylates)_n polymers into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes. The in vitro fibrillation kinetics coupled to transmission electron microscopy (TEM) is employed to investigate the role of hybrid-vesicles on Aβ_1-40 fibrillation without destroying the vesicular membrane. Both polymers, when embedded in hybrid-vesicles (up to 20%) significantly prolonged the fibrillation lag phase (t_lag) compared to a small acceleration in the presence of DOPC vesicles, irrespective of the amount of polymers inside the hybrid-vesicles. Along with this notable retardation effect, a morphological transformation of the amyloid's secondary structures to amorphous aggregates or the absence of fibrillar structures when interacting with the hybrid-vesicles is confirmed by TEM and circular dichroism (CD) spectroscopy.     

Concentration-Dependent Interactions of Amphiphilic PiB Derivative Metal Complexes with Amyloid Peptides Aβ and Amylin**

Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents. The attachment of a metal complex to amyloid recognition units typically leads to a decrease in peptide affinity. We show here that by separating a macrocyclic GdL chelate and a PiB targeting unit with a long hydrophobic C10 linker, it is possible to attain nanomolar affinities for both Aβ_1-40 (K_d=4.4 nm ) and amylin (K_d=4.5 nm ), implicated, respectively in Alzheimer's disease and diabetes. The Scatchard analysis of surface plasmon resonance data obtained for a series of amphiphilic, PiB derivative GdL complexes indicate that their Aβ_1-40 or amylin binding affinity varies with their concentration, thus micellar aggregation state. The GdL chelates also affect peptide aggregation kinetics, as probed by thioflavin-T fluorescence assays. A 2D NMR study allowed identifying that the hydrophilic region of Aβ_1-40 is involved in the interaction between the monomer peptide and the Gd³⁺ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using ¹¹¹In labeled analogues. Their pancreatic uptake, ∼3 %ID g⁻¹, is promising to envisage amylin imaging in diabetic animals.     

Evaluation of Aβ fibrillization inhibitory effect by a PEG-peptide conjugate based on an Aβ peptide fragment with intramolecular FRET

A PEG-peptide conjugate based on an amyloid β peptide fragment was synthesized. The formed amyloid protofibril-like aggregates induced intramolecular FRET. It proved to be useful as a bioprobe to evaluate the inhibitory effect of organic molecules toward amyloid fibrillization.     

AFM and fluorescence spectrascopy investigation for disaggregation of existing Aβ fibrils by baicalein

The wavelength for the peak of fluorescence emission of thioflavin T（ThT） was changed from 445 nm to 481 nm when ThT was added in Aβ solution which indicating theβ-sheet structure of Aβ fibril.The significant decrease in the intensity of fluorescence at 481 nm was observed when the baicalein was added in mixed solution of Aβ and ThT,suggesting that the depolymerization of Aβ fibrils happened and there were Aβfibrils left to react with ThT to keep the initial fluorescence intensity.And the existing Aβfibrils are disaggregated by baicalein in a time- and dose-dependent manner.AFM images of the morphologies of the Aβ_1-42 fibrils obviously changed smaller and more dispersive when baicalein added indicating also the depolymerization of Aβ.The results demonstrate a basis for development of a potential herb drug candidate for the treatment of Alzheimer’s disease（AD）.     

Direct Oxidation of N‐Benzylamides to Aldehydes or Ketones by N‐Bromosuccinimide

A simple and efficient approach for the one‐pot transformation of N‐benzylamides to aldehydes or ketones under mild conditions was reported. All the 20 substrates gave moderate to excellent oxidative yields under the optimized conditions. Our study may provide a new approach for the one‐pot synthesis of aldehydes or ketones from the corresponding amides.     

A Novel Approach to Improve the Detectability of CO2 by GC Analysis

A novel stochastic resonance algorithm was employed to enhance the signal-to-noise ratio (SNR) of signals of analytical chemistry.By using a gas chromatographic data set,it was proven that the SNR was greatly improved and the quantitative relationship between concentrations and chromatographic responses remined simultancously.The linear range was extended beyond the instrumental detection limit.     

A novel route to synthesize diphenylene by the catalytic effect of GaP nanocrystals

Diphenylene was synthesized directly from benzene under the catalytic effect of GaP nanocrystals, and the effect of GaP nanocrystals content was studied. The experimental results showed that no reactions took place without GaP nanocrystals. The more the GaP nanocrystals added, the more the reaction complete. Furthermore, at high temperatures (450-480℃), when the content of GaP nanocrystals was high enough, almost all benzene polymerized and the yield of diphenylene was rather high. On the contrast, even if there are enough GaP nanocrystals in the reaction mixture, almost no polymerization reaction took place at low temperature (for example, 250-300℃), and the yield of diphenylene was very poor. The analytical results of XRD, IR, elemental analysis and NMR proved that the sample was truly diphenylene.     

A “Low-Molecular” Approach to the Identification of Microorganisms by MALDI Mass Spectrometry

A new approach to the identification of microorganisms is presented. It includes the transformation of their MALDI mass spectra aimed at reducing mass scale by one order of magnitude and the use of standard software for building mass spectral libraries of low-molecular compounds and library searches. A library of 728 transformed (“rescaled”) mass spectra of 182 strains for some Streptococcus species was built. With this library, the rate of true microorganism identification was estimated by cross-comparison between library mass spectra (internal validation of the approach). The true identification rate was 84% for three Streptococcus species, which corresponds to the average trueness of species identification by MALDI as found in the literature. The proposed approach to identification can be considered as a method of choice for solving identification problems under consideration.     

Manipulation and capture of Aβ amyloid fibrils and monomers by DC insulator gradient dielectrophoresis (DC-iGDEP)

Here we report a novel method for the manipulation and concentration of Aβ amyloid fibrils, implicated in Alzheimer's disease, using DC insulating gradient dielectrophoresis (DC-iGDEP). Fibril enrichment was found to be ～400%. Simulations suggest that capture of the full range of amyloid protein aggregates is possible with optimized device design.     

Ammoxidation of ethylene to acetonitrile over chromium or cobalt alumina catalysts prepared by sol–gel method

A series of Cr/Al₂O₃ and Co/Al₂O₃ catalysts were tested in the selective ammoxidation of ethylene to acetonitrile. Catalysts were prepared either by sol–gel method or by impregnation with chromium or cobalt acetylacetonate salts. Physicochemical properties of catalysts were accomplished by several techniques such as chemical analysis, physisorption of N₂, X-ray diffraction (XRD), ²⁷Al MAS NMR, UV–Visible diffuse reflectance (DRS) and Raman spectroscopy and temperature programmed reduction of H₂ (H₂–TPR). Textural analysis reveals that mesoporous materials with pronounced surface areas were obtained using sol–gel procedure while impregnation of the support produces a moderate decrease of its surface area and pore volume. XRD analysis confirms the presence of highly dispersed metal species which reside essentially on the surface and measure less than 4 nm. Furthermore, ²⁷Al MAS NMR shows that for xerogels, part of metal species occupies sites on/in A1₂O₃ in close vicinity of octahedral ²⁷Al. This, apparently, is not the case for aerogels. For Cr/Al₂O₃ catalysts, isolated Cr⁶⁺, mono and polychromate species were identified using DRS, Raman Spectroscopy and H₂–TPR which seem to play a key role in the ammoxidation of ethylene. Furthermore, for cobalt doped catalysts, CoAl₂O₄ was identified as active phase on the basis of DRS and H₂–TPR results. From the supercritical drying, it results generally better catalysts than catalysts calcined by ordinary procedure which leads to inactive agglomerated Co₃O₄ and CoO–Al₂O₃ phase.     

The conversion of methane to methanol: a reaction catalyzed by I+ or I2(+)?

The gas-phase reactions of I+ and I2(+) with methane were studied to determine which species is involved in the oxidation of methane to methyl sulfate, an intermediate in the production of methanol. We found that while I+ reacts readily with methane, I2(+) does not react in our experimental reaction conditions. Reaction products and rate constants are measured and reported. In addition, ab initio calculations were carried out to further understand the reaction mechanism. A revised mechanism of catalysis is proposed which is in excellent agreement with available experimental data and our theoretical computations.     

The Michael Addition of Enamines to Propenamidines. A Convenient Synthesis of 2β-Amidinoethylcyclo-Alkanones by Amidinoethylation Reaction

A variety of propenamidines 3 have been reacted with enamines of cyclopentanone and cyclohexanone giving after hydrolysis of the Stork enamine 6, 2-β-amidinoethylcyclopentanones 8 and -hexanones 7. This reaction illustrates the electrophilic character of the C=C double bond due to the conjugated amidine function, thus providing with propenamidines 3 a new class of Michael acceptors for enamines.     

A new approach to the spectral analysis of liquid membrane oscillators by Gábor transformation

Liquid membrane oscillators very frequently have an irregular oscillatory behavior. Fourier transformation cannot be used for these nonstationary oscillations to establish their power spectra. This important point seems to be overlooked in the field of chemical oscillators. A new approach is presented here based on Gábor transformation allowing one to obtain power spectra of any kind of oscillations that can be met experimentally. The proposed Gábor analysis is applied to a liquid membrane oscillator containing a cationic surfactant. It was found that the power spectra are strongly influenced by the presence of various added substances.     

A novel approach to the quantification of urinary aryl-propionamide-derived SARMs by UHPLC–MS/MS

A simple and sensitive procedure for the quantification of two commonly abused aryl-propionamide-derived selective androgen receptor modulators (SARMs), namely S-4 (GTx-007, andarine) and S-22 (GTx-024, MK-2866, ostarine, enobosarm), has been described. Urine samples were prepared for analysis by means of a dispersive liquid–liquid microextraction using methanol and chloroform as dispersive and extracting solvents, respectively. Factors that might influence the extraction process as well as their optimum conditions were evaluated by Box–Benken and central composite designs. After extraction, the analytes were quantified by UHPLC–MS/MS. The proposed procedure was validated on human urine samples. As a result, for both SARMs the detection limits were observed at 0.05 ng/mL and calibration curves were linear in the concentration range of 0.25–50 ng/mL with the coefficient of determination of 0.998.     

A New Approach to C60-Containing Polyphosphazenes by Polymerization of Phosphonitrile Chloride Trimer in the Presence of C60

A novel synthetic strategy was developed to prepare polyphosphazenes containing C60 moieties. Thus, the phosphonitrile chloride trimer underwent thermal ring-opening polymerization （ROP） in the presence of C60 molecules to yield the reactive macromolecular intermediate, C60-containing poly（dichlorophosphazene）. And then, the other groups could be linked to the phosphazene backbone by nucleophilic substitution reaction of the chlorine atoms in this intermediate to produce a series of C60-containing polyphosphazene. The polymer exhibits good solubility in common organic solvents and is thermally stable.     

A versatile route to the synthesis of 1-substituted β-carbolines by a single step Pictet-Spengler cyclization

A one-step conversion of l-tryptophan and activated aldehydes (1,2-dicarbonyl compounds) directly to 1-substituted β-carbolines without formation of the tetrahydro derivatives under modified Pictet-Spengler conditions was described. Moreover, a practical application for the synthesis of a natural 1-substituted β-carboline, luzongerine A, isolated from Illigera luzonensis was also successfully carried out utilizing this protocol. The effects of synthetic compounds 11 and 11a on nitric oxide (NO) production in LPS/IFN-γ stimulated RAW 264.7 macrophage cells were evaluated in vitro. They displayed significant dose-dependent inhibition of inducible nitric oxide synthase (iNOS).     

Annelation of the thiazole ring to 1,2,4-triazines by tandem AN—AN or SN H—SN H reactions

The reactions of 3-aryl-1,2,4-triazines with aromatic thioamides and 4-arylthiosemicarbazides in acetic anhydride at room temperature afforded cyclic products of the tandem nucleophilic addition reactions, viz., tetrahydrothiazolo[4,5-e]-annelated 1,2,4-triazines, in good yields. The latter underwent aromatization in the presence of potassium permanganate.     

A New Protocol to Generate Catalytically Active Species of Group 4–6 Metals by Organosilicon-Based Salt-Free Reductants

Herein, we provide a new protocol to reduce various transition-metal complexes by using organosilicon compounds in a salt-free fashion with the great advantage of generating pure low-valent metal species and metallic(0) nanoparticles, in sharp contrast to reductant-derived salt contaminants obtained by reduction with metal reductants. The organosilicon derivatives 1,4-bis(trimethylsilyl)-2,5-cyclohexadiene ( 1 a ), 1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene ( 1 b ), 1,4-bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene ( 2 a ), 2,5-dimethyl-1,4-bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene ( 2 b ), 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene ( 2 c ), and 1,1′-bis(trimethylsilyl)-1H,1′H-4,4′-bipyridinylidene ( 3 ) all served as versatile reductants for early transition-metal complexes and produced only easy-to-remove organic compounds, such as trimethylsilylated compounds and the corresponding aromatics, for example, benzene, toluene, pyrazine, and 4,4′-bipyridyl, as the byproducts. The high solubility of the reductants in organic solvents enabled us to monitor the catalytic reactions directly and to detect any catalytically active species so that we could elucidate the reaction mechanism.