Bridge‐Clamp Bis(tetrazine)s with [N]8 π‐Stacking Interactions and Azido‐s‐Aryl Tetrazines: Two Classes of Doubly Clickable Tetrazines

Click chemistry at a tetrazine core is useful for bioorthogonal labeling and crosslinking. Introduced here are two new classes of doubly clickable s‐aryl tetrazines synthesized by Cu‐catalyzed cross‐coupling. Homocoupling of o‐brominated s‐aryl tetrazines leads to bis(tetrazine)s structurally characterized by tetrazine cores arranged face‐to‐face. [N]₈ π‐stacking interactions are essential to the conformation. Upon inverse electron demand Diels–Alder (iEDDA) cycloaddition, the bis(tetrazine)s produce a unique staple structure. The o‐azidation of s‐aryl tetrazines introduces a second proximal intermolecular clickable function that leads to double click chemistry opportunities. The stepwise introduction of fluorophores and then iEDDA cycloaddition, including bioconjugation to antibodies, was achieved on this class of tetrazines. This method extends to (thio)etherification, phosphination, trifluoromethylation and the introduction of various bioactive nitrogen‐based heterocycles.     

Investigation of artifacts caused by deuterium background correction in the determination of phosphorus by electrothermal atomization using high-resolution continuum source atomic absorption spectrometry

The artifacts created in the measurement of phosphorus at the 213.6-nm non-resonance line by electrothermal atomic absorption spectrometry using line source atomic absorption spectrometry (LS AAS) and deuterium lamp background correction (D₂ BC) have been investigated using high-resolution continuum source atomic absorption spectrometry (HR-CS AAS). The absorbance signals and the analytical curves obtained by LS AAS without and with D₂ BC, and with HR-CS AAS without and with automatic correction for continuous background absorption, and also with least-squares background correction for molecular absorption with rotational fine structure were compared. The molecular absorption due to the suboxide PO that exhibits pronounced fine structure could not be corrected by the D₂ BC system, causing significant overcorrection. Among the investigated chemical modifiers, NaF, La, Pd and Pd + Ca, the Pd modifier resulted in the best agreement of the results obtained with LS AAS and HR-CS AAS. However, a 15% to 100% higher sensitivity, expressed as slope of the analytical curve, was obtained for LS AAS compared to HR-CS AAS, depending on the modifier. Although no final proof could be found, the most likely explanation is that this artifact is caused by a yet unidentified phosphorus species that causes a spectrally continuous absorption, which is corrected without problems by HR-CS AAS, but which is not recognized and corrected by the D₂ BC system of LS AAS.     

Exploring structure and dynamics of the diaquotriamminezinc(II) complex by QM/MM MD simulation

The structural and dynamical properties of the cis-(O-Zn-O angle approximately 90 degrees) and trans-(O-Zn-O angle approximately 180 degrees) isomers of the model diaquotriamminezinc(II) complex in aqueous solution have been evaluated using the hybrid quantum mechanical/molecular mechanical molecular dynamics simulation approach at ab initio Hartree-Fock level. In both complexes, the first hydration shell contains five ligands (two water and three ammonia molecules) arranged in a trigonal bipyramidal geometry. In the metastable cis-isomer two different bond lengths of 2.34 and 2.13 A are observed for the Zn-Oax and Zn-Oeq bonds, respectively. The trans-isomer shows the maximum of the Zn-O distance at 2.26 A. The Zn-N bond distances in both cases are approximately 2.12 A. A geometrical transformation of the cis-isomer into the trans-isomer was observed after 11.5 ps of simulation, and the trans-isomer then remained stable throughout the whole simulation time of 30 ps. A comparative study for both isomers has been performed in terms of radial distribution functions, coordination number distributions, angular distribution functions, tilt and theta angle distributions, ligands' mean residence time, ion-ligand stretching frequencies, and the vibrational and librational motions of water ligands. The results are compared with the data for the previously studied zinc-monoamine and -diamine complexes.     

High-resolution NMR spectroscopy under the fume hood

This work reports the possibility to acquire high-resolution (1)H NMR spectra with a fist-sized NMR magnet directly installed under the fume hood. The small NMR sensor based on permanent magnets was used to monitor the trimerization of propionaldehyde catalyzed by indium trichloride in real time by continuously circulating the reaction mixture through the magnet bore in a closed loop with the help of a peristaltic pump. Thanks to the chemical selectivity of NMR spectroscopy the progress of the reaction can be monitored on-line by determining the concentrations of both reactant and product from the area under their respective lines in the NMR spectra as a function of time. This in situ measurement demonstrates that NMR probes can be used in chemistry laboratories, e.g. for reaction optimization, or installed at specific points of interest along industrial process lines. Therefore, it will open the door for the implementation of feedback control based on spectroscopic NMR data.     

Vitamin B12-derivatives-enzyme cofactors and ligands of proteins and nucleic acids

B(12)-cofactors play important roles in the metabolism of microorganisms, animals and humans. Microorganisms are the only natural sources of B(12)-derivatives, and the latter are "vitamins" for other B(12)-requiring organisms. Some B(12)-dependent enzymes catalyze complex isomerisation reactions, such as methylmalonyl-CoA mutase. They need coenzyme B(12), an organometallic B(12)-derivative, to induce enzymatic radical reactions. Another group of widely relevant enzymes catalyzes the transfer of methyl groups, such as methionine synthase, which uses methylcobalamin as cofactor. This tutorial review covers structure and reactivity of B(12)-derivatives and structural aspects of their interactions with proteins and nucleotides, which are crucial for the efficient catalysis by the important B(12)-dependent enzymes, and for achieving and regulating uptake and transport of B(12)-derivatives.     

Electrospray Post-Ionization Mass Spectrometry of Electrosurgical Aerosols

The feasibility of electrospray (ES) ionization of aerosols generated by electrosurgical disintegration methods was investigated. Although electrosurgery itself was demonstrated to produce gaseous ions, post-ionization methods were implemented to enhance the ion yield, especially in those cases when the ion current produced by the applied electrosurgical method is not sufficient for MS analysis. Post-ionization was implemented by mounting an ES emitter onto a Venturi pump, which is used for ion transfer. The effect of various parameters including geometry, high voltage setting, flow parameters, and solvent composition was investigated in detail. Experimental setups were optimized accordingly. ES post-ionization was found to yield spectra similar to those obtained by the REIMS technique, featuring predominantly lipid-type species. Signal enhancement was 20- to 50-fold compared with electrosurgical disintegration in positive mode, while no improvement was observed in negative mode. ES post-ionization was also demonstrated to allow the detection of non-lipid type species in the electrosurgical aerosol, including drug molecules. Since the tissue specificity of the MS data was preserved in the ES post-ionization setup, feasibility of tissue identification was demonstrated using different electrosurgical methods.     

Determination of cadmium and lead in beverages after leaching from pewter cups using graphite furnace atomic absorption spectrometry

Two simple methods have been developed to determine cadmium and lead in different kinds of beverages and vinegar leached from pewter cups produced in Brazil. Leaching experiments have been carried out with different solutions: beer, sugar cane spirit, red and white wine, vinegar and a 3% acetic acid solution. The solutions were kept in cups with and without solder for 24 h. Lead and cadmium have been determined using graphite furnace atomic absorption spectrometry with deuterium background correction. The limits of detection were 0.05 and 1.4 μg L⁻¹, and the characteristic mass was 1.0 pg and 19 pg for Cd and Pb, respectively. With the developed methods it was possible to determine accurately cadmium and lead by direct analysis in these liquids and to evaluate the leaching of these metals from pewter cups. The results presented in this work show that pewter cups are not cadmium- and lead-free; this point goes against the manufacturers’ declaration that their products are lead-free.     

Determination of fluorine in tea using high-resolution molecular absorption spectrometry with electrothermal vaporization of the calcium mono-fluoride CaF

High-resolution continuum source molecular absorption of the calcium mono-fluoride molecule CaF in a graphite furnace has been used to determine fluorine in tea after acid digestion, alkaline solubilization and preparation of a conventional aqueous infusion. The strongest absorption ‘line’ of the CaF molecule is at 606.440 nm, which is part of the rotational fine structure of the X²Σ⁺ − A²Π electronic transition; it has a bond dissociation energy of 529 kJ mol⁻¹, which is comparable with other molecules used for fluorine determination. One advantage of using Ca as the molecule-forming reagent is that spectral interferences are extremely unlikely in the spectral range of its strongest absorption. Another advantage is that Ca acts both as molecule forming reagent and chemical modifier, so that no other reagent has to be added, making the method very simple. The only disadvantage is that Ca has a somewhat negative influence on the graphite tube lifetime. The limit of detection was found to be 0.16 mg L⁻¹ F, corresponding to 1.6 ng F absolute, and the calibration curve was linear in the range between 0.5 and 25 mg L⁻¹ with a correlation coefficient of R = 0.9994. The results obtained for a certified tea reference material were in agreement with the certified value on a 95% confidence level. There was also no difference between the results obtained after an acid digestion and an alkaline solubilization for 10 tea samples, based on a paired t-test. The values found in the 10 samples ranged between 42 μg g⁻¹ and 87 μg g⁻¹ F; the tea infusions contained between 21 μg g⁻¹ and 56 μg g⁻¹ F, with an extraction rate between 48% and 74%.