Towards Substrate–Reagent Interaction of Lochmann–Schlosser Bases in THF: Bridging THF Hides Potential Reaction Site of a Chiral Superbase

The metalation of N,N-dimethylaminomethylferrocene in THF by the superbasic mixture of ⁿBuLi/KO^tBu proceeds readily at low temperatures to afford a bimetallic Li₂K₂ aggregate containing ferrocenyl anions and tert-butoxide. Starting from an enantiomerically enriched ortho-lithiated aminomethylferrocene, an enantiomerically pure superbase can be prepared. The molecular compound exhibits superbasic behavior deprotonating N,N-dimethylbenzylamine in the α-position and is also capable of deprotonating toluene. Quantum chemical calculations provide insight into the role of the bridging THF molecule to the possible substrate–reagent interaction. In addition, a benzylpotassium alkoxide adduct gives a closer look into the corresponding reaction site of the Lochmann–Schlosser base that is reported herein.     

Antireflection ln2O3 coatings of self‐organized TiO2 nanotube layers prepared by atomic layer deposition

We report on the uniform anti‐reflection coating of TiO₂ nanotube layers with a secondary material – indium trioxide (In₂O₃) – by atomic layer deposition (ALD). We provide for the first time the detailed evidence of the ALD deposited coating inside nanotubes for three different tube layers with aspect ratio up to ≈80, which is so far the highest aspect ratio reported for ALD‐processed self‐organized anodic TiO₂ nanotubes. We show that uniform In₂O₃coating of the nanotubes strongly influences the overall reflectance of the layers due to intrinsic properties of In₂O₃. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Designing logical codon reassignment – Expanding the chemistry in biology

Over the last decade, the ability to genetically encode unnatural amino acids (UAAs) has evolved rapidly. The programmed incorporation of UAAs into recombinant proteins relies on the reassignment or suppression of canonical codons with an amino-acyl tRNA synthetase/tRNA (aaRS/tRNA) pair, selective for the UAA of choice. In order to achieve selective incorporation, the aaRS should be selective for the designed tRNA and UAA over the endogenous amino acids and tRNAs. Enhanced selectivity has been achieved by transferring an aaRS/tRNA pair from another kingdom to the organism of interest, and subsequent aaRS evolution to acquire enhanced selectivity for the desired UAA. Today, over 150 non-canonical amino acids have been incorporated using such methods. This enables the introduction of a large variety of structures into proteins, in organisms ranging from prokaryote, yeast and mammalian cells lines to whole animals, enabling the study of protein function at a level that could not previously be achieved. While most research to date has focused on the suppression of ‘non-sense’ codons, recent developments are beginning to open up the possibility of quadruplet codon decoding and the more selective reassignment of sense codons, offering a potentially powerful tool for incorporating multiple amino acids. Here, we aim to provide a focused review of methods for UAA incorporation with an emphasis in particular on the different tRNA synthetase/tRNA pairs exploited or developed, focusing upon the different UAA structures that have been incorporated and the logic behind the design and future creation of such systems. Our hope is that this will help rationalize the design of systems for incorporation of unexplored unnatural amino acids, as well as novel applications for those already known.     

Determination of biogenic amines in food samples using derivatization followed by liquid chromatography/mass spectrometry

A liquid chromatography (LC)/mass spectrometry method was developed for the determination of selected biogenic amines in various fish and other food samples. It is based on a precolumn derivatization of the amines with succinimidylferrocenyl propionate under formation of the respective amides and their reversed-phase liquid-chromatographic separation with subsequent electrospray ionization mass-spectrometric detection. Deuterated putescine, cadaverine, and histamine are added prior to the derivatization as internal standards that are coeluted, thus allowing excellent reproducibility of the analysis to be achieved. Depending on the analyte, the limits of detection were between 1.2 and 19.0 mg/kg, covering between 2 and 3 decades of linearity. The limit of detection and the linear range for histamine are suitable for the surveillance of the only defined European threshold for biogenic amines in fish samples. Compared with the established ortho-phthalaldehyde (OPA)/LC/fluorescence method, the newly developed method allows an unambiguous identification of the biogenic amines by their mass spectra in addition to only retention times, a fivefold acceleration of the separation, and independency from the sample matrix owing to the isotope-labeled internal standards. Various fish, calamari, and salami samples were successfully analyzed with the new method and validated with an independent OPA/LC/fluorescence method.     

The FEAST algorithm for large eigenvalue problems

We consider the eigensolver named FEAST that was introduced by Polizzi in 2009 [1]. This solver, tailored to the (partial) solution of large sparse (generalized) eigenproblems offers good potential for parallelism and showed good robustness in our experiments. We briefly introduce the algorithm, point out some problems and give two examples. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Progress in capillary electrophoresis coupled to matrix-assisted laser desorption/ionization - time of flight mass spectrometry

In this review the most important techniques developed to hyphenate CE to MALDI-TOF-MS are summarized. The principles of the different interfaces and ways to solve the hyphenation problem are explained and discussed in detail. The most important applications especially in the proteomic field are reviewed, and the advantages of CE-MALDI-TOF-MS for the analysis of these compounds compared to other techniques such as ESI-MS are exhaustingly discussed from a critical point of view. CE coupled to MALDI-TOF-MS has started to overpass traditionally used CE-coupling techniques, especially CE-ESI-MS, offering the possibility to analyze samples of interest even weeks after CE analysis and using multiplexing systems for high-sample throughput.     

Substituted pyrazinecarboxamides: synthesis and biological evaluation

Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid) with various ring-substituted aminothiazoles or anilines yielded a series of amides. The syntheses, analytical and spectroscopic data of thirty newly prepared compounds are presented. Structure-activity relationships between the chemical structures and the anti-mycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluated compounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substituted pyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacterium tuberculosis H(37)Rv (54-72% inhibition). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-tert-butyl-6-chloro-N-(4-methyl-1,3-thiazol-2-yl)pyrazine-2-carboxamide (8, MIC =31.25 micromol x mL(-1)). The most active inhibitors of oxygen evolution rate in spinach Molecules 2006, 11,243 chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5-bromo-2-hydroxyphenyl)- pyrazine-2-carboxamide (27, IC(50) = 41.9 micromol x L(-1)) and 5-tert-butyl-6-chloro-N-(1,3- thiazol-2-yl)-pyrazine-2-carboxamide (4, IC50 = 49.5 micromol x L(-1)).     

Fiber-optic flow-through sensor for online monitoring of glucose

A new microdialysis-based glucose-sensing system with an integrated fiber-optic hybrid sensor is presented. Design and dimensions of the cell are adapted for its coupling with commercially available microdialysis techniques, thereby providing a new system for continuous glucose monitoring. The glucose level is detected via oxygen consumption which occurs as a consequence of enzymatic reaction between immobilized glucose oxidase and glucose. The use of gas-permeable Tygon tubing ensures complete and constant air-saturation of the measuring fluid in the cell. Nevertheless, a reference oxygen optode is used to detect and to compensate response changes caused by events like bacterial growth, temperature fluctuations, or failure of the peristaltic pump. In contrast to widely used electrochemical sensors, the response of the microdialysis-based fiber-optic glucose sensor is highly selective, making this sensor approach particularly advantageous for continuous glucose monitoring of patients in intensive care units. The effects of flow rate, pH, temperature, and common interferences on the sensor response are presented and discussed in detail. The sensor is evaluated in vitro using a 3-day continuous test in glucose-spiked plasma. The ability to measure glucose in humans is demonstrated by coupling the flow-through cell and commercially available microdialysis catheter CMA60. A 24-h monitoring test using this setup is successfully applied to a healthy volunteer.     

Heterodyne mixing of laser fields for temporal gating of high-order harmonic generation

The concept of heterodyne mixing of laser fields is theoretically applied to the process of high-harmonic generation to enhance and modulate the kinetic energy of the active electron on subcycle time scales. A very small amount of intensity in the heterodyne field creates a significant modification of the electron kinetic energy, due to its amplification by the strong fundamental field in the kinetic-energy term, in which the heterodyne mixing occurs. Quantum calculations are carried out to verify the predictions of the classical results, demonstrating very good qualitative and quantitative agreement. Applications of the heterodyne-mixing concept are the extension of the harmonic cutoff to higher photon energies and the temporal gating of attosecond pulse production.