Borane Adducts of Aromatic Phosphorus Heterocycles: Synthesis,Crystallographic Characterization and Reactivity of a Phosphinine-B(C6F5)3 Lewis Pair

A phosphinine-borane adduct of a Me₃Si-functionalized phosphinine and the Lewis acid B(C₆F₅)₃ has been synthesized and characterized crystallographically for the first time. The reaction strongly depends on the nature of the substituents in the α-position of the phosphorus heterocycle. In contrast, the reaction of B₂H₆ with various substituted phosphinines leads to an equilibrium between the starting materials and the phosphinine–borane adducts that is determined by the Lewis basicity of the phosphinine. The novel phosphinine borane adduct ( 6 -B(C₆F₅)₃) shows rapid and facile insertion and [4+2] cycloaddition reactivity towards phenylacetylene. A hitherto unknown dihydro-1-phosphabarrelene is formed with styrene. The reaction with an ester provides a new, facile and selective route to 1-R-phosphininium salts. These salts then undergo a [4+2] cycloaddition in the presence of Me₃Si−C≡CH and styrene to cleanly form unprecedented derivatives of 1-R-phosphabarrelenium salts.     

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery**

Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.     

Heavy Chains: Synthesis,Reactivity and Decomposition of Interpnictogen Chains with Terminal Diaryl Bismuth Fragments

In this work, we report the preparation of multiple interpnictogen chain compounds with three consecutive pnictogen atoms and terminal Ar₂Bi fragments (Ar=Ph, Mes). Symmetrical compounds of the form Ar₂Bi−E(tBu)−Bi₂Ar ( 1 : Ar=Ph, E=P; 2 : Ar=Ph, Mes, E=As) as well as ternary interpnictogen compounds of the form Ar₂Bi−E¹(tBu)−E²tBu₂ (Ar=Ph, Mes; 4 : E¹=P, E²=As; 5 : E¹=P, E²=Sb; 6 : E¹=As, E²=P) were prepared. The decomposition in solution at room temperature and under the influence of light was studied for compounds 1 – 6 . The reactivity of 1_Ph and 2_Ph with the small N-heterocyclic carbene 1,3,4,5-tetramethylimidazol-2-ylidene (Me₂IMe) was also studied. In the case of 1_Ph , the formation and consecutive decomposition of Me₂IMe=PtBu ( 8 ) was observed in solution. Hence, it was shown that 1_Ph can react as a “masked phosphinidene”. In the case of 2_Ph , no reaction with Me₂IMe was observed. All isolated compounds were analysed by NMR and IR spectroscopy, mass spectrometry, elemental analysis and single-crystal X-ray diffraction.     

[2+3] Amide Cages by Oxidation of [2+3] Imine Cages – Revisiting Molecular Hosts for Highly Efficient Nitrate Binding

The pollution of groundwater with nitrate is a serious issue because nitrate can cause several diseases such as methemoglobinemia or cancer. Therefore, selective removal of nitrate by efficient binding to supramolecular hosts is highly desired. Here we describe how to make [2+3] amide cages in very high to quantitative yields by applying an optimized Pinnick oxidation protocol for the conversion of corresponding imine cages. By NMR titration experiments of the eight different [2+3] amide cages with nitrate, chloride and hydrogen sulfate we identified one cage with an unprecedented high selectivity towards nitrate binding vs. chloride (S=705) or hydrogensulfate (S>13500) in CD₂Cl₂/CD₃CN (1 : 3). NMR experiments as well as single-crystal structure comparison of host-guest complexes give insight into structure-property-relationships.     

Clickable report tags for identification of modified peptides by mass spectrometry

The identification and quantification of modified peptides are critical for the functional characterization of post-translational protein modifications (PTMs) to elucidate their biological function. Nowadays, quantitative mass spectrometry coupled with various bioinformatic pipelines has been successfully used for the determination of a wide range of PTMs. However, direct characterization of low abundant protein PTMs in bottom-up proteomic workflow remains challenging. Here, we present the synthesis and evaluation of tandem mass spectrometry tags (TMT) which are introduced via click-chemistry into peptides bearing alkyne handles. The fragmentation properties of the two mass tags were validated and used for screening in a model system and analysis of AMPylated proteins. The presented tags provide a valuable tool for diagnostic peak generation to increase confidence in the identification of modified peptides and potentially for direct peptide-PTM quantification from various experimental conditions.     

Metal Assisted Synthesis of Cationic Sulfidobismuth Cubanes in Ionic Liquids

Bi₂S₃ was dissolved in the presence of either AuCl/PtCl₂ or AgCl in the ionic liquids [BMIm]Cl ⋅ xAlCl₃ (BMIm=1-n-butyl-3-methylimidazolium; x=4–4.3) through annealing the mixtures at 180 or 200 °C. Upon cooling to room temperature, orange, air-sensitive crystals of [BMIm](Bi₄S₄)[AlCl₄]₅ ( 1 ) or Ag(Bi₇S₈)[S(AlCl₃)₃]₂[AlCl₄]₂ ( 2 ) precipitated, respectively. 1 did not form in the absence of AuCl/PtCl₂, suggesting an essential role of the metal cations. X-ray diffraction on single-crystals of 1 revealed a monoclinic crystal structure that contains (Bi₄S₄)⁴⁺ heterocubanes and [AlCl₄]⁻ tetrahedra as well as [BMIm]⁺ cations. The intercalation of the ionic liquid was confirmed via solid state NMR spectroscopy, revealing unusual coupling behavior. The crystal structure of 2 consists of (Bi₇S₈)⁵⁺ spiro-dicubanes, [S(AlCl₃)₃]²⁻ tetrahedra triples, isolated [AlCl₄]⁻ tetrahedra, and heavily disordered silver(I) cations. No cation ordering took place in 2 upon slow cooling to 100 K.     

Arene Ruthenium(II) Complexes Bearing the κ-P or κ-P,κ-S Ph2P(CH2)3SPh Ligand

Neutral [Ru(η⁶-arene)Cl₂{Ph₂P(CH₂)₃SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthalene: 2a, 2c and 2d) and cationic [Ru(η⁶-arene)Cl(Ph₂P(CH₂)₃SPh-κP,κS)]X complexes (arene = mesitylene, 1,4-dihydronaphthalene; X = Cl: 3b, 3e; arene = benzene, mesitylene, indane, 1,2,3,4-tetrahydronaphthalene, and 1,4-dihydronaphthalene; X = PF₆: 4a–4e) complexes were prepared and characterized by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy and also by single-crystal X-ray diffraction analyses. The stability of the complexes has been investigated in DMSO. Complexes have been assessed for their cytotoxic activity against 518A2, 8505C, A253, MCF-7 and SW480 cell lines. Generally, complexes exhibited activity in the lower micromolar range; moreover, they are found to be more active than cisplatin. For the most active ruthenium(II) complex, 4b, bearing mesitylene as ligand, the mechanism of action against 8505C cisplatin resistant cell line was determined. Complex 4b induced apoptosis accompanied by caspase activation.     

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.     

Turbulence transition and the edge of chaos in pipe flow

The linear stability of pipe flow implies that only perturbations of sufficient strength will trigger the transition to turbulence. In order to determine this threshold in perturbation amplitude we study the edge of chaos which separates perturbations that decay towards the laminar profile and perturbations that trigger turbulence. Using the lifetime as an indicator and methods developed in Skufca et al., Phys. Rev. Lett. 96, 174101 (2006), we show that superimposed on an overall 1/Re scaling predicted and studied previously there are small, nonmonotonic variations reflecting folds in the edge of chaos. By tracing the motion in the edge we find that it is formed by the stable manifold of a unique flow field that is dominated by a pair of downstream vortices, asymmetrically placed towards the wall. The flow field that generates the edge of chaos shows intrinsic chaotic dynamics.     

Line tension at fluid membrane domain boundaries measured by micropipette aspiration

Line tension is a determinant of fluid phase domain formation kinetics and morphology in lipid bilayer membranes, which are models for biological membrane heterogeneity. We describe the first direct measurement of this line tension by micropipette aspiration. Our data are analyzed with a model that does not rely on independently measured (and composition dependent) secondary parameters, such as bending stiffness or membrane viscosities. Line tension is strongly composition dependent and decreases towards a critical consolute point in a quasiternary room temperature phase diagram.