Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus

Glucose can modify proteins in human blood, forming early glycation products (e.g., Amadori compounds), which can slowly degrade to advanced glycation endproducts (AGEs). AGEs contribute significantly to complications of diabetes mellitus and, thus, represent markers of advanced disease stages. They are, however, currently unsuitable for early diagnosis and therapeutic monitoring. Here, we report sensitive strategies to identify and relatively quantify protein glycation sites in human plasma samples obtained from type 2 diabetes mellitus (T2DM) patients and age-matched nondiabetic individuals using a bottom-up approach. Specifically, Amadori peptides were enriched from tryptic digests by boronic acid affinity chromatography, separated by reversed-phase chromatography, and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori peptides studied here were 20 peptides resembling 19 glycation sites in six human proteins detected at statistically significantly higher levels in T2DM than in the normoglycemic controls. Four positions appeared to be unique for T2DM within the detection limit. All 19 glycation sites represent promising new biomarker candidates for early diagnosis of T2DM and adequate therapeutic control, as they may indicate early metabolic changes preceding T2DM. Graphical Abstract

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On vibrations in non-linear,forced, friction-excited systems

To accelerate the development of non-linear, friction-excited systems, i.e. automotive friction brakes, novel test procedures are being developed. These include the study of the system's forced vibrations. However, there is a lack of knowledge concerning feasible test procedures, the assessment of the gathered data, and the possible vibration phenomena. In this context, the contribution at hand discusses vibrations in non-linear, forced, friction-excited systems. In the pre-flutter regime proposed criteria for identification of parameter regions in which limit cycle oscillations can occur are challenged. In the post-flutter regime frequency spectra for different excitation conditions are studied. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Insights on the Lewis Superacid Al(OTeF5)3: Solvent Adducts,Characterization and Properties**

Preparation and characterization of the dimeric Lewis superacid [Al(OTeF₅)₃]₂ and various solvent adducts is presented. The latter range from thermally stable adducts to highly reactive, weakly bound species. DFT calculations on the ligand affinity of these Lewis acids were performed in order to rank their remaining Lewis acidity. An experimental proof of the Lewis acidity is provided by the reaction of solvent-adducts of Al(OTeF₅)₃ with [PPh₄][SbF₆] and OPEt₃, respectively. Furthermore, their reactivity towards chloride and pentafluoroorthotellurate salts as well as (CH₃)₃SiCl and (CH₃)₃SiF is shown. This includes the formation of the dianion [Al(OTeF₅)₅]²⁻.     

Diamond electrode facilitated electrosynthesis of water and wastewater treatment oxidants

While diamond electrodes have been commonly used to generate ^?OH to treat a variety of persistent water and wastewater micropollutants, mass transfer limitations and the non-selective, short-lived nature of the ^?OH restrict the degradation to the solution at, or near, the electrode surface. However, diamond electrodes can generate oxidizing species that facilitate micropollutant degradation in the bulk water solution. These include persulfate, sulfate radicals, peroxodiphosphate, ferrate, permanganate, reactive chlorine species, hydrogen peroxide, and ozone, which have been reported during electrochemical treatment of water with diamond electrodes. Although still restricted to specialized applications, recent studies, summarized in this review, have proven the electrogeneration of these additional oxidant species to be effective. They have shown the adaptability and potential of diamond electrode-based water treatment to mitigate the presence of micropollutants in water.     

Mechanochemically Triggered Topology Changes in Expanded Porphyrins

A hitherto unexplored class of molecules for molecular force probe applications are expanded porphyrins. This work proves that mechanical force is an effective stimulus to trigger the interconversion between Hückel and Möbius topologies in [28]hexaphyrin, making these expanded porphyrins suitable to act as conformational mechanophores operating at mild (sub-1 nN ) force conditions. A straightforward approach based on distance matrices is proposed for the selection of pulling scenarios that promote either the planar Hückel topology or the three lowest lying Möbius topologies. This approach is supported by quantum mechanochemical calculations. Force distribution analyses reveal that [28]hexaphyrin selectively allocates the external mechanical energy to molecular regions that trigger Hückel–Möbius interconversions, explaining why certain pulling scenarios favor the Hückel two-sided topology and others favor Möbius single-sided topologies. The meso-substitution pattern on [28]hexaphyrin determines whether the energy difference between the different topologies can be overcome by mechanical activation.     

Inorganic–Organic Heteropolyacid–Gold(I) Hybrids: Structures and Catalytic Applications

Gold(I)‐polyoxometalate hybrid complexes 1 – 4 ([PPh₃AuMeCN]_xH_4?xSiW₁₂O₄₀, x=1–4) were synthesized and characterized. The structure of the primary gold(I)–polyoxometalate 1 (x=1) was fully ascertained by XRD, FTIR, ³¹P and ²⁹Si magic‐angle spinning (MAS) NMR, mass spectroscopy, and SEM–energy dispersive X‐ray spectroscopy (EDX) techniques. Moreover, this complex exhibited better catalytic activity and selectivity compared with standard, homogeneous, gold catalysts in the new rearrangement of propargylic gem‐diesters.     

A Straightforward Approach towards Cyclic Photoactivatable Tubulysin Derivatives

The development of a new photolabile protecting group containing an additional allyl functionality allows the synthesis of cyclic photoactivatable natural products. Cyclization occurs between the allyl moiety in the protecting group and a second double bond in the target molecule by means of ring‐closing metathesis. Cyclization should increase the metabolic stability towards proteases. On the other hand, the conformational change should cause diminished biological activity. As illustrated for tubulysin derivatives, cyclic and photoactivatable drug candidates can easily be obtained in only two steps from simple building blocks through Ugi reaction and ring‐closing metathesis. The photolabile protecting group is introduced by means of the isocyanide component during the Ugi reaction.     

SrIr9In18 – A Structurally Complex Intermetallic Compound with Sr@Ir4In12, Ir@In8 and Ir@In9 Building Units

Single crystals of SrIr₉In₁₈ were obtained by induction melting of the elements in a glassy carbon crucible followed by annealing at 1070 K. SrIr₉In₁₈ was structurally characterized by X-ray powder and single crystal diffraction: P4 m2, a = 811.21(5), c = 854.49(5) pm, wR₂ = 0.0511, 1223 F² values, and 46 variables. The structure is of a new type. The basic building units are Ir@In₈ (distorted square-prismatic, square anti-prismatic and bicapped trigonal prismatic coordination) and Ir@In₉ (distorted trigonal prismatic coordination) polyhedra, which condense to a three-dimensional network, which leaves large cavities for the strontium cations, which are coordinated to four iridium and twelve indium atoms. The [Ir₉In₁₈]^2– polyanionic network is stabilized through Ir–In (267–290 pm) and In–In (302–354 pm) bonding.     

Specific interaction of desthiobiotin lipids and water-soluble biotin compounds with streptavidin

As shown for biotin lipids (Ref. 1), the formation of perfect 2-D crystalline streptavidin domains can also be observed in the plane of desthiobiotin lipid monolayers. The binding constant of streptavidin with desthiobiotin (K_a = 5·10¹³ mol⁻¹) is lower than that with biotin (K_a = 10¹⁵ mol⁻¹) (Ref. 2). By adding free biotin into the subphase a competitive replacement and a detaching of the streptavidin domains from the desthiobiotin lipid monolayer takes place. Streptavidin domains built at receptor lipid monolayers are still functional. As could be shown, there are two biotin binding sites at each protein molecule that are fully accessible to biotin (Ref. 1). This can be proven by the interaction with biotinylated ferritin and fluoresceinated biotin. Further coupling of an anti-FITC-antibody can proceed and a second protein layer can be formed. Using a bifunctional biotin linker a second crystalline streptavidin layer underneath the first one can be obtained.