Non‐thermal plasma‐induced apoptosis in yeast Saccharomyces cerevisiae

The effect of non‐thermal plasma generated by the direct current (DC) corona discharge in the mode of transition spark is studied on a yeast Saccharomyces cerevisiae. The exposure to plasma increases production of reactive oxygen species (ROS) in cells, possibly causing the induction of apoptosis. To clarify the mechanism of apoptosis, its induction is tested not only on a wild strain of S. cerevisiae, but also on mutant strains: A deletion mutant Δyca1 without yeast metacaspase proves that in S. cerevisiae the apoptosis occurs partly by the caspase‐independent pathway. A petite strains with mutation in the mitochondria do not show pronounced ROS formation, but in spite of this, apoptosis is detected. Hence, mitochondrial ROS probably do not play an important role in induction of apoptosis.     

Thiophenylazobenzene: An Alternative Photoisomerization Controlled by Lone-Pair⋅⋅⋅π Interaction

Azoheteroarene photoswitches have attracted attention due to their unique properties. We present the stationary photochromism and ultrafast photoisomerization mechanism of thiophenylazobenzene (TphAB). It demonstrates impressive fatigue resistance and photoisomerization efficiency, and shows favorably separated (E)- and (Z)-isomer absorption bands, allowing for highly selective photoconversion. The (Z)-isomer of TphAB adopts an unusual orthogonal geometry where the thiophenyl group is perfectly perpendicular to the phenyl group. This geometry is stabilized by a rare lone-pair⋅⋅⋅π interaction between the S atom and the phenyl group. The photoisomerization of TphAB occurs on the sub-ps to ps timescale and is governed by this interaction. Therefore, the adoption and disruption of the orthogonal geometry requires significant movement along the inversion reaction coordinates (CNN and NNC angles). Our results establish TphAB as an excellent photoswitch with versatile properties that expand the application possibilities of AB derivatives.     

Catalytically Active Hollow Fiber Membranes with Enzyme-Embedded Metal–Organic Framework Coating

Metal–organic frameworks (MOFs) are suitable enzyme immobilization matrices. Reported here is the in situ biomineralization of glucose oxidase (GOD) into MOF crystals (ZIF-8) by interfacial crystallization. This method is effective for the selective coating of porous polyethersulfone microfiltration hollow fibers on the shell side in a straightforward one-step process. MOF layers with a thickness of 8 μm were synthesized, and fluorescence microscopy and a colorimetric protein assay revealed the successful inclusion of GOD into the ZIF-8 layer with an enzyme concentration of 29±3 μg cm⁻². Enzymatic activity tests revealed that 50 % of the enzyme activity is preserved. Continuous enzymatic reactions, by the permeation of β-d -glucose through the GOD@ZIF-8 membranes, showed a 50 % increased activity compared to batch experiments, emphasizing the importance of the convective transport of educts and products to and from the enzymatic active centers.     

Direct Introduction of an Alkylsulfonamido Group on C-sites of Isomeric Dicarba-closo-dodecaboranes: The Influence of Stereochemistry on Inhibitory Activity against the Cancer-Associated Carbonic Anhydrase IX Isoenzyme

Carbonic anhydrase IX (CA IX), a tumor-associated metalloenzyme, represents a validated target for cancer therapy and diagnostics. Herein, we report the inhibition properties of isomeric families of sulfonamidopropyl-dicarba-closo-dodecaboranes group(s) prepared using a new direct five-step synthesis from the corresponding parent cages. The protocol offers a reliable solution for synthesis of singly and doubly substituted dicarba-closo-dodecaboranes with a different geometric position of carbon atoms. The closo-compounds from the ortho- and meta-series were then degraded to corresponding 11-vertex dicarba-nido-undecaborate(1−) anions. All compounds show in vitro enzymatic activity against CA IX in the low nanomolar or subnanomolar range. This is accompanied by clear isomer dependence of the inhibition constant (K_i) and selectivity towards CA IX. Decreasing trends in K_i and selectivity index (S_I) values are observed with increasing separation of the cage carbon atoms. Interactions of compounds with the active sites of CA IX were explored with X-ray crystallography, and eight high-resolution crystal structures uncovered the structural basis of inhibition potency and selectivity.     

Structure of Zinc and Nickel Histidine Complexes in Solution Revealed by Molecular Dynamics and Raman Optical Activity

The histidine residue has an exceptional affinity for metals, but solution structure of its complexes are difficult to study. For zinc and nickel complexes, Raman and Raman optical activity (ROA) spectroscopy methods to investigate the link between spectral shapes and the geometry were used. The spectra were recorded and interpreted on the basis of ionic equilibria, molecular dynamics, ab initio molecular dynamics, and density functional theory. For zwitterionic histidine the dominant tautomer was determined by the decomposition of experimental spectra into calculated subspectra. An octahedral structure was found to prevail for the ZnHis₂ complex in solution, in contrast to a tetrahedral arrangement in the crystal phase. The solution geometry of NiHis₂ is more similar to the octahedral structure found by X-ray. The Raman and ROA structural determinations of metal complexes are dependent on extensive computations, but reveal unique information about the studied systems.     

Studies on the collision‐induced dissociation of adipoR agonists after electrospray ionization and their implementation in sports drug testing

AdipoR agonists are small, orally active molecules capable of mimicking the protein adiponectin, which represents an adipokine with antidiabetic and antiatherogenic effects. Two adiponectin receptors were reported in the literature referred to as adipoR1 and adipoR2. Activation of these receptors stimulates mitochondrial biogenesis and results in an improved oxidative metabolism (via adipoR1) and increased insulin sensitivity (via adipoR2). Hence, adipoR agonists are potentially performance enhancing substances and targets of proactive and preventive anti‐doping measures. In this study, two adipoR agonists termed AdipoRon and 112254 as well as two isotopically labeled internal standards (ISTDs) were synthesized in three‐step reactions. The products were fully characterized by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) computation. Collision‐induced dissociation pathways following electrospray ionization were suggested based on the determined elemental compositions of product ions, comparison to product ions derived from labeled analogs (ISTDs), H/D‐exchange experiments and the results of DFT calculations. The most abundant product ions were found at m/z 174, tentatively assigned to protonated 1‐benzyl‐1,2,3,4‐tetrahydropyridine for AdipoRon, and m/z 207, suggested as protonated 1‐(4‐methoxybenzyl)piperazine, for 112254. Notably, the loss of the heterocyclic ring (i.e. piperazine and piperidine, respectively) in a supposedly intramolecular elimination reaction was observed in both cases. A qualitative determination of both AdipoR agonists in human plasma was established and fully validated for doping control purposes. Validation items such as recovery (86–89%), specificity, linearity, lower limit of detection (1 ng/ml), intraday (3–18%) and interday (5–16%) precision as well as ion suppression or enhancement were determined. Based on these findings adipoR agonists can be implemented in sports drug testing procedures. Copyright © 2015 John Wiley & Sons, Ltd.     

Encapsulation of Functional Organic Compounds in Nanoglass for Optically Anisotropic Coatings

A novel approach is presented for the encapsulation of organic functional molecules between two sheets of 1 nm thin silicate layers, which like glass are transparent and chemically stable. An ordered heterostructure with organic interlayers strictly alternating with osmotically swelling sodium interlayers can be spontaneously delaminated into double stacks with the organic interlayers sandwiched between two silicate layers. The double stacks show high aspect ratios of >1000 (typical lateral extension 5000 nm, thickness 4.5 nm). This newly developed technique can be used to mask hydrophobic functional molecules and render them completely dispersible in water. The combination of the structural anisotropy of the silicate layers and a preferred orientation of molecules confined in the interlayer space allows polymer nanocomposite films to be cast with a well‐defined orientation of the encapsulated molecules, thus rendering the optical properties of the nanocoatings anisotropic.     

One‐Step Synthesis of a [20]Silafullerane with an Endohedral Chloride Ion

Silicon analogues of the most prominent carbon nanostructures, namely, hollow spheroidals such as C₆₀ and the fullerene family, have been unknown to date. Herein we show that discrete Si₂₀ dodecahedra, stabilized by an endohedral guest and valence saturation, are accessible in preparative yields through a chloride‐induced disproportionation reaction of hexachlorodisilane in the presence of tri(n‐butyl)amine. X‐ray crystallography revealed that each silicon dodecahedron contains an endohedral chloride ion that imparts a net negative charge. Eight chloro substituents and twelve trichlorosilyl groups are attached to the surface of each cluster in a strictly regioregular arrangement, a thermodynamically preferred substitution pattern according to quantum‐chemical assessment. Our results demonstrate that the wet‐chemical self‐assembly of a complex, monodisperse Si nanostructure is possible under mild conditions starting from simple Si₂ building blocks.