Novel proresolving aspirin-triggered DHA pathway

Endogenous mechanisms in the resolution of acute inflammation are of interest because excessive inflammation underlies many pathologic abnormalities. We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. The complete stereochemistry of AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated triene system essential for bioactivity were established by matching biological materials with stereochemically pure isomers prepared by organic synthesis. AT-(NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose-dependent fashion whereby neither a Δ(15)-trans-isomer nor DHA was effective. With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. These results indicate that AT-(NPD1/PD1) is a potent anti-inflammatory proresolving molecule.     

Electron tunneling through sensitizer wires bound to proteins

We report a quantitative theoretical analysis of long-range electron transfer through sensitizer wires bound in the active-site channel of cytochrome P450cam. Each sensitizer wire consists of a substrate group with high binding affinity for the enzyme active site connected to a ruthenium-diimine through a bridging aliphatic or aromatic chain. Experiments have revealed a dramatic dependence of electron transfer rates on the chemical composition of both the bridging group and the substrate. Using combined molecular dynamics simulations and electronic coupling calculations, we show that electron tunneling through perfluorinated aromatic bridges is promoted by enhanced superexchange coupling through virtual reduced states. In contrast, electron flow through aliphatic bridges occurs by hole-mediated superexchange. We have found that a small number of wire conformations with strong donor–acceptor couplings can account for the observed electron tunneling rates for sensitizer wires terminated with either ethylbenzene or adamantane. In these instances, the rate is dependent not only on electronic coupling of the donor and acceptor but also on the nuclear motion of the sensitizer wire, necessitating the calculation of average rates over the course of a molecular dynamics simulation. These calculations along with related recent findings have made it possible to analyze the results of many other sensitizer-wire experiments that in turn point to new directions in our attempts to observe reactive intermediates in the catalytic cycles of P450 and other heme enzymes.     

Zur Tryptophanreaktion

Ohne Zusammenfassung     

Die Anwendung des Magnesiums als Reagens

Ohne Zusammenfassung     

Liquid-Phase Epitaxy of (Hg,Cd)Te on CdTe Substrates by a Vertical Dipping Technique

Hg_1−xCd_xTe layers on CdTe substrates were grown from Te-rich melt solutions by a vertical dipping technique using a special quasi-closed system with ground-glass sealing. Results are good reproducibilities of the electrical properties after annealing in Hg-rich atmosphere (p77 ≈ 2 · 10¹⁶ cm⁻³ μ77 ≈ 500 cm² V⁻¹ s⁻¹) and of the x-value, respectively. A horizontal position of the substrate downwards to the melt solution yields, in difference to a vertical one, to homogeneous layer thicknesses. Short meltback steps before growth leads to sharper profiles of composition.