Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase B

The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine oxidation. Mechanistic and electron paramagnetic (EPR) spectroscopic data supports the conclusion that the reaction proceeds through a radical manifold. This data provides the first example of a biorelevant synthetic model for monoamine oxidase B activity.     

The Nature of the UC Double Bond: Pushing the Stability of High‐Oxidation‐State Uranium Carbenes to the Limit

Treatment of [K(BIPM^MesH)] (BIPM^Mes={C(PPh₂NMes)₂}^2?; Mes=C₆H₂‐2,4,6‐Me₃) with [UCl₄(thf)₃] (1 equiv) afforded [U(BIPM^MesH)(Cl)₃(thf)] ( 1 ), which generated [U(BIPM^Mes)(Cl)₂(thf)₂] ( 2 ), following treatment with benzyl potassium. Attempts to oxidise 2 resulted in intractable mixtures, ligand scrambling to give [U(BIPM^Mes)₂] or the formation of [U(BIPM^MesH)(O)₂(Cl)(thf)] ( 3 ). The complex [U(BIPM^Dipp)(μ‐Cl)₄(Li)₂(OEt₂)(tmeda)] ( 4 ) (BIPM^Dipp={C(PPh₂NDipp)₂}^2?; Dipp=C₆H₃‐2,6‐iPr₂; tmeda=N,N,N′,N′‐tetramethylethylenediamine) was prepared from [Li₂(BIPM^Dipp)(tmeda)] and [UCl₄(thf)₃] and, following reflux in toluene, could be isolated as [U(BIPM^Dipp)(Cl)₂(thf)₂] ( 5 ). Treatment of 4 with iodine (0.5 equiv) afforded [U(BIPM^Dipp)(Cl)₂(μ‐Cl)₂(Li)(thf)₂] ( 6 ). Complex 6 resists oxidation, and treating 4 or 5 with N‐oxides gives [{U(BIPM^DippH)(O)₂‐ (μ‐Cl)₂Li(tmeda)] ( 7 ) and [{U(BIPM^DippH)(O)₂(μ‐Cl)}₂] ( 8 ). Treatment of 4 with tBuOLi (3 equiv) and I₂ (1 equiv) gives [U(BIPM^Dipp)(OtBu)₃(I)] ( 9 ), which represents an exceptionally rare example of a crystallographically authenticated uranium(VI)–carbon σ bond. Although 9 appears sterically saturated, it decomposes over time to give [U(BIPM^Dipp)(OtBu)₃]. Complex 4 reacts with PhCOtBu and Ph₂CO to form [U(BIPM^Dipp)(μ‐Cl)₄(Li)₂(tmeda)(OCPhtBu)] ( 10 ) and [U(BIPM^Dipp)(Cl)(μ‐Cl)₂(Li)(tmeda)(OCPh₂)] ( 11 ). In contrast, complex 5 does not react with PhCOtBu and Ph₂CO, which we attribute to steric blocking. However, complexes 5 and 6 react with PhCHO to afford (DippNPPh₂)₂C?C(H)Ph ( 12 ). Complex 9 does not react with PhCOtBu, Ph₂CO or PhCHO; this is attributed to steric blocking. Theoretical calculations have enabled a qualitative bracketing of the extent of covalency in early‐metal carbenes as a function of metal, oxidation state and the number of phosphanyl substituents, revealing modest covalent contributions to U?C double bonds.     

Fully automated chip-based nanoelectrospray combined with electron transfer dissociation for high throughput top-down proteomics

The conventional protocol for protein identification by electrospray ionization mass spectrometry (MS) is based on enzymatic digestion which renders peptides to be analyzed by liquid chromatography-MS and collision-induced dissociation (CID) multistage MS, in the so-called bottom-up approach. Though this method has brought a significant progress to the field, many limitations, among which, the low throughput and impossibility to characterize in detail posttranslational modifications in terms of site(s) and structure, were reported. Therefore, the research is presently focused on the development of procedures for efficient top-down fragmentation of intact protein ions. In this context, we developed here an approach combining fully automated chip-based-nanoelectrospray ionisation (nanoESI), performed on a NanoMate robot, with electron transfer dissociation (ETD) for peptide and top-down protein sequencing and identification. This advanced analytical platform, integrating robotics, microfluidics technology, ETD and alternate ETD/CID, was tested and found ideally suitable for structural investigation of peptides and modified/functionalized peptides as well as for top-down analysis of medium size proteins by tandem MS experiments of significantly increased throughput and sensitivity. The obtained results indicate that NanoMate-ETD and ETD/CID may represent a viable alternative to the current MS strategies, with potential to develop into a method of routine use for high throughput top-down proteomics.     

Novel Multifunctional Graphene Sheets with Encased Au/Ag Nanoparticles for Advanced Electrochemical Analysis of Organic Compounds

This work is the first presentation of the synthesis of few‐layer graphene decorated with gold and silver nanoparticles (Gr–Au–Ag) by chemical vapor deposition over a catalytic system formed of bimetallic Au–Ag nanoclusters supported on MgO and with methane used as the source of carbon. The sheetlike morphology of the graphene nanostructures, with mean sizes in the range of hundreds of nanometers, was observed by high‐resolution electron microscopy. The distinctive feature found in all the samples was the regular rectangular or square shapes. This multi‐component organic–inorganic nanomaterial was used to modify a platinum substrate and subsequently employed for the detection of carbamazepine, an anti‐convulsion drug. UV/Vis spectroscopy revealed that a strong hypochromism occurred over time, after mixing solutions of graphene–Au–Ag with carbamazepine. This can be attributed to π–π stacking between the aromatic groups of the two compounds. Linear sweep voltammetry (LCV) provided evidence that the modified platinum substrate presented a significant electrocatalytic reaction toward the oxidation of carbamazepine. The intensity of the current was found to increase by up to 2.5 times, and the oxidation potential shifted from +1.5 to +1.35 V(Ag/AgCl) in comparison with the unmodified electrode. Electrochemical impedance spectroscopy (EIS) was further used to thoroughly assess the activity of the platinum electrode that was modified by the deposition of the Gr‐Au‐Ag composites in the presence of various concentrations of carbamazepine. The experimental EIS records were used for the generation of an equivalent electrical circuit, based on the charge‐transfer resistance (R_ct), Warburg impedance (Z_D), solution resistance (R_s), and a constant phase element (CPE) that characterizes the non‐ideal interface capacitive responses.     

Suppression of the Jahn-Teller distortion in a six-coordinate copper(II) complex by doping it into a host lattice

The electronic structures of [Cu(terpy)(2)](2+) and [Cu(bpp)(2)](2+) (bpp = 2,6-di[pyrazol-1-yl]pyridine) are different, when doped into [M(bpp)(2)][BF(4)](2) (M(2+) = Fe(2+) or Zn(2+)). The [Cu(terpy)(2)](2+) dopant is a typical pseudo-Jahn-Teller elongated copper(II) center. However, the [Cu(bpp)(2)](2+) sites show EPR spectra consistent with a tetragonally compressed {d(z(2))}(1) configuration.     

Plasma- and vacuum-ultraviolet (VUV) photo-polymerisation of N- and O-rich thin films

Nitrogen (N)- and oxygen (O)-rich organic thin films were deposited by vacuum-ultraviolet (VUV)-assisted photo-chemical polymerisation of flowing ethylene (C₂H₄)–ammonia (NH₃) and C₂H₄–nitrous oxide (N₂O) mixtures of varying ratios, R, respectively. The reaction mechanism of these binary gas mixtures was investigated as a function of the wavelength, λ, of two near-mono-chromatic VUV sources. Surface-near compositions of these “UV-PE:N” and “UV-PE:O” films were determined by X-ray photoelectron (XPS), and by Fourier transform (reflection–absorption) infrared (FTIR) spectroscopies. The two types of films were compared with plasma polymers deposited using low-pressure radio-frequency (r.f.) glow discharges in similar gas flow mixtures, “PPE:N” and “PPE:O”. VUV-photochemistry appears to be superior to plasma-chemistry in its capability to produce nearly “mono-functional” organic thin films, ones that are rich in primary amines, –NH₂, and in carboxylic acid groups, –COOH, respectively.     

Profiling and sequence analysis of gangliosides in human astrocytoma by high-resolution mass spectrometry

In this preliminary investigation, a low-grade astrocytoma (AcT) is investigated by high-resolution (HR) mass spectrometry (MS) aiming at characterization of gangliosides with potential biomarker value. The research was conducted towards a comparative mapping of ganglioside expression in AcT, its surrounding tissue (ST) and a normal control brain tissue (NT). HR MS was conducted in the negative ion mode nanoelectrospray ionization (nanoESI). Fragmentation analysis was carried out by collision-induced dissociation (CID) MS²–MS^4. Due to the high resolving power and mass accuracy, by comparative mapping of the ganglioside extracts from AcT, ST and NT, under identical conditions, 37 different species in AcT, 40 in ST and 56 in NT were identified. AcT and ST were found to contain 18 identical ganglioside components. Among all three specimens, ST extract presented the highest levels of sialylation, fucosylation and acetylation, a feature which might be correlated to the tumor expansion in the adjacent brain area. MS mapping indicated also that AcT, ST and NT share one doubly deprotonated molecule at m/z 1063.31, attributable to GT1(d18:1/18:0) or GT1(d18:0/18:1). CID MS²–MS⁴ on these particular ions detected in AcT and ST provided data supporting GT1c isomer in the investigated astrocytoma tissue. Our results show that HR MS has a remarkable potential in brain cancer research for the determination of tumor-associated markers and for their structural determination.

Determination of some frequently used antibiotics in waste waters using solid phase extraction followed by high performance liquid chromatography with diode array and mass spectrometry detection

This study is focused on the determination of some important antibiotics from different classes in waste water samples using solid phase extraction followed by high performance liquid chromatography with two detectors, diode array and mass spectrometer in positive ionisation mode. The investigated antibiotics include three penicillins (amoxicillin, ampicillin, penicillin G), two cephalosporins (ceftazidime, ceftriaxone), and two tetracyclines (tetracycline, doxycycline). The studied antibiotics were extracted from waste water samples using hydrophilic-lipophilic balanced cartridges. The extraction of antibiotics from water matrices was tested at several pH values. The best recoveries were obtained at pH 3 and 7 respectively. Depending on the nature of antibiotic, the limits of detection and quantification were obtained in the range of 0.07–0.92 µg mL^?1 and 0.21–2.77 µg mL^?1 respectively. Influent and effluent waste water samples were collected from a Waste Water Treatment Plant from Romania in order to detect the studied antibiotics. The antibiotics detected in the influent waste water samples were ceftriaxone (334 µg L^?1), tetracycline (146 µg L^?1) and doxycycline (110 µg L^?1). In effluent waste water samples no target antibiotics were detected.      

Sterilization validation for medical devices at IRASM microbiological laboratory—Practical approaches

EN ISO 11137 established regulations for setting or substantiating the dose for achieving the desired sterility assurance level.The validation studies can be designed in particular for different types of products. Each product needs distinct protocols for bioburden determination and sterility testing.The Microbiological Laboratory from Irradiation Processing Center (IRASM) deals with different types of products, mainly for the VD_max²⁵ method. When it comes to microbiological evaluation the most challenging was cotton gauze. A special situation for establishing the sterilization validation method appears in cases of cotton packed in large quantities. The VD_max²⁵ method cannot be applied for items with average bioburden more than 1000 CFU/pack, irrespective of the weight of the package. This is a method limitation and implies increased costs for the manufacturer when choosing other methods.For microbiological tests, culture condition should be selected in both cases of the bioburden and sterility testing. Details about choosing criteria are given.