Aryl Pyrazoles from Photocatalytic Cycloadditions of Arenediazonium.

A photocatalytic synthesis of 1,5-diaryl pyrazoles from arenediazoniums and arylcyclopropanols is reported. The reaction proceeded under mild conditions (rt, 20 min) with catalytic [Ru(bpy)3]2+ under blue-light irradiation and exhibited compatibility with several functional groups (e.g., I, SF5, SO2NH2, N3, CN) and perfect levels of regiocontrol. Mechanistic studies (luminescence spectroscopy, CV, DFT, radical trapping, quantum yield determination) documented an initial oxidative quenching of the excited photocatalyst and the operation of a radical-chain mechanism.

Combined Photoredox and Iron Catalysis for the Cyclotrimerization of Alkynes.

Successful combinations of visible-light photocatalysis with metal catalysis have recently enabled the development of hitherto unknown chemical reactions. Dual mechanisms from merging metal-free photocatalysts and earth-abundant metal catalysts are still in their infancy. We report a photo-organo-iron-catalyzed cyclotrimerization of alkynes by photoredox activation of a ligand-free Fe catalyst. The reaction operates under very mild conditions (visible light, 20 °C, 1 h) with 1-2 mol % loading of the three catalysts (dye, amine, FeCl2 ).

S100B Serum Level is Independent of Moderate Alcohol Intoxication. / S100B-Serumniveau ist unabhängig von moderatem Alkoholkonsum.

OBJECTIVE: In Germany, among patients with minor head injury (MHI), the incidence of coexisting alcohol intoxication is indicated up to 50%. The neurological symptoms of patients with MHI may be caused or altered by alcohol intoxication, this could mislead to further, potential harmful, diagnostic steps or to misinterpretation of the symptoms and to non-execution of necessary treatments. In order to decide which patients need further diagnostics by CCT, S100B has been proposed as a potential selection criterion. On the other hand, studies have hypothesized that alcohol intoxication may lead to elevated S100B serum levels. Therefore, the present study aims to investigate the relationship between the blood ethyl alcohol concentration and the S100B serum concentration in an experimental setting in young human adult volunteers. METHODS: In a cohort of 58 healthy volunteers, serum S100B concentration and blood ethyl alcohol concentration were measured before and after liberately drinking alcohol. The study was approved by the local Ethics Committee of the Medical Faculty Mannheim (Ethics Committee II, AZ 2012-272 N-MA). Instantaneous analysis of the samples was carried out using state-of-the art automated measuring systems. (Analyzer Cobas e411, Roche and Analyzer Dimension Vista 1500, Siemens). RESULTS: After drinking, alcohol levels ranged from 0,23 to 1,92 g/l. The S100B value ranged from to 0,021 to 0,115 µg/l after alcohol consumption (S100B standard value < 0,11 µg/l). By calculating the Pearson correlation of empirical correlation after drinking alcohol with r = 0.01181, a correlation between serum S100B concentration and ethyl alcohol concentration is not probable. The S100B concentrations were independent on the alcohol intake in low to medium alcohol levels. CONCLUSION: A relevant alcohol blood concentration (~ 1 g/l), in otherwise healthy volunteers, does not affect the serum concentration of S100B. S100B may be a useful brain injury marker in low to moderate drunken patients.

Dichromatic Photocatalytic Substitutions of Aryl Halides with a Small Organic Dye.

Photocatalytic bond activations are generally limited by the photon energy and the efficiency of energy and electron transfer processes. Direct two-photon processes provide sufficient energy but the ultra-short lifetimes of the excited states prohibit chemical reactions. The commercial dye 9,10-dicyanoanthracene enabled photocatalytic aromatic substitutions of non-activated aryl halides. This reaction operates under VIS-irradiation via sequential photonic, electronic, and photonic activation of the simple organic dye. The resultant highly reducing excited photocatalyst anion readily effected C-H, C-C, C-P, C-S, and C-B bond formations. Detailed synthetic, spectroscopic, and theoretical studies support a biphotonic catalytic mechanism.

Electrochemiluminescence Bioassays with a Water-Soluble Luminol Derivative Can Outperform Fluorescence Assays.

The most efficient and commonly used electrochemiluminescence (ECL) emitters are luminol, [Ru(bpy)3 ]2+ , and derivatives thereof. Luminol stands out due to its low excitation potential, but applications are limited by its insolubility under physiological conditions. The water-soluble m-carboxy luminol was synthesized in 15 % yield and exhibited high solubility under physiological conditions and afforded a four-fold ECL signal increase (vs. luminol). Entrapment in DNA-tagged liposomes enabled a DNA assay with a detection limit of 3.2 pmol L-1 , which is 150 times lower than the corresponding fluorescence approach. This remarkable sensitivity gain and the low excitation potential establish m-carboxy luminol as a superior ECL probe with direct relevance to chemiluminescence and enzymatic bioanalytical approaches.

Aromatic Chlorosulfonylation by Photoredox Catalysis.

Visible-light photoredox catalysis enables the efficient synthesis of arenesulfonyl chlorides from anilines. The new protocol involves the convenient in situ preparation of arenediazonium salts (from anilines) and the reactive gases SO2 and HCl (from aqueous SOCl2 ). The photocatalytic chlorosulfonylation operates at mild conditions (room temperature, acetonitrile/water) with low catalyst loading. Various functional groups are tolerated (e.g., halides, azides, nitro groups, CF3 , SF5 , esters, heteroarenes). Theoretical and experimental studies support a photoredox-catalysis mechanism.

Macromol. Rapid Commun. 10/2016.

Back Cover: Sustainable polyamides with side groups and stereocenters are synthesized starting from L-menthone. This terpenoid ketone is transformed in a one-step synthesis into a chiral lactam, which is then polymerized via ring-opening polymerization (ROP). The beneficial properties of these polymers are thus introduced via the structure and chirality of the lactam monomer. Further details can be found in the article by M. Winnacker*, M. Neumeier, X. Zhang, C. M. Papadakis, and B. Rieger on page 851.

Sustainable Chiral Polyamides with High Melting Temperature via Enhanced Anionic Polymerization of a Menthone-Derived Lactam.

Polyamides are very important polymers that find applications from commodities up to the automotive and biomedical sectors, and their impact is continuously growing. The synthesis of structurally significant, chiral, and sustainable polyamides is described via a new, convenient, and solvent-free anionic polymerization of a biobased ε-lactam, which is obtained from the renewable terpenoid ketone l-menthone in a one-step synthesis. These polyamides are shown to have outstanding structural and thermal properties, which are thus introduced via the structure and chirality of the natural lactam monomer and which are discussed and compared with those of petroleum-based, established, and commercial polyamide Nylon-6. X-ray data reveal a remarkable degree of crystallinity in these green polymers and emphasize the impact of their structural features on the resulting properties.

41.8 degrees C whole body hyperthermia as an adjunct to chemotherapy induces prolonged T cell activation in patients with various malignant diseases.

Whole body hyperthermia (WBH) has been used as an adjunct to radio-/chemotherapy in patients with various malignant diseases. Although clear evidence is still missing, it has been hypothesized that an activation of the immune system might contribute to the therapeutic effect of WBH. To examine whether a treatment with 60-minute 41.8 degrees C WBH as an adjunct to chemotherapy (WBH-CT) induces an activation of T cells, blood samples were collected at numerous time points before and up to 48 h post-treatment. The aim of this study was to examine the effect of WBH-CT on the expression of a broad range of activation markers on peripheral blood lymphocytes (PBL), on serum cytokines and intracellular cytokine levels in T cells, and the capacity of these cells to proliferate. Immediately after 41.8 degrees C WBH-CT treatment, a drastic increase in peripheral natural killer (NK) cells ( P<0.05) and CD56+ cytotoxic T lymphocytes (CTL; P<0.01) in the patients' peripheral blood was observed. At 5 h post-treatment, the percentages of both effector cell types had returned to baseline levels. This transient phenomenon was accompanied by a short period of reduced T cell activity, indicated by diminished serum levels of soluble interleukin-2 receptors (sIL-2R) at 3 h post-WBH-CT ( P<0.05) and decreased lymphocytic proliferation at the same point in time. This first phase was followed by a marked but short-lived increase in the patients' serum levels of interleukin-6 (IL-6; P<0.01) during the first 5 h following treatment, with a subsequent decrease to baseline levels at 24 h and significantly increased serum levels of tumor necrosis factor-alpha (TNF-alpha) at 0 h ( P<0.01), 3 h ( P<0.05), 5 h ( P<0.05) and 24 h ( P<0.01) post-WBH-CT. The third phase of the immunological consequences of WBH-CT consisted of an increase in the percentage of peripheral cytotoxic T lymphocytes (CTL) expressing CD56, reaching a maximum at 48 h post-WBH ( P<0.01). Furthermore, the percentage of CD4+ T cells expressing the T cell activation marker CD69 increased nearly two-fold over time, reaching its maximum at 48 h ( P<0.05). As an additional marker for T cell activation, serum levels of sIL-2R increased markedly ( P<0.01), reaching maximum levels at the same point in time. Elevated intracellular concentrations of interferon-gamma (IFN-gamma) and/or TNF-alpha in CD8+ T cells were found in 4 out of 5 patients at 24 h post-WBH-CT. Since similar changes were not observed in patients receiving chemotherapy alone, this is the first study to provide evidence for prolonged WBH-CT-induced activation of human T cells.