Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade

Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of styrene derivatives leading to chiral substituted 1,2-azido alcohols via enzymatic asymmetric epoxidation, followed by regioselective azidolysis, affording the azido alcohols with up to two contiguous stereogenic centers. A newly isolated two-component flavoprotein styrene monooxygenase StyA proved to be highly selective for epoxidation with a nicotinamide coenzyme biomimetic as a practical reductant. Coupled with azide as a nucleophile for regioselective ring opening, this chemo-enzymatic cascade produced highly enantioenriched aromatic α-azido alcohols with up to >99% conversion. A bi-enzymatic counterpart with halohydrin dehalogenase-catalyzed azidolysis afforded the alternative β-azido alcohol isomers with up to 94% diastereomeric excess. We anticipate our biocatalytic cascade to be a starting point for more practical production of these chiral compounds with two-component flavoprotein monooxygenases. A one-pot enzymatic cascade for the asymmetric azidohydroxylation of styrenes leads to chiral 1,2-azido alcohols with up to two stereocenters

Zum Zusammenhang zwischen Rational-Emotiver Theorie und Attributionstheorie: Irrationale Gedanken als Determinanten depressogener Ursachenzuschreibungen und maladaptiver Emotionen

Die Rational-Emotive Theorie (RET) nach Ellis sowie die Attributionstheorien betrachten Kognitionen als notwendige und hinreichende Bedingungen bestimmter Emotionen. Zudem beinhalten beide Theoriekomplexe spezifische Darstellungen von Kognitionen, die der psychischen Gesundheit abträglich sind: Diese sind in der RET durch irrationale Gedanken („ich muss unbedingt...“) in der Attributionstheorie insbesondere durch den depressogenen Attributionsstil gekennzeichnet. Auf der Grundlage dieser theoretischen Gemeinsamkeiten überprüft eine experimentelle Fragebogenstudie mittels unterschiedlicher Szenarien in permutierten Darbietungen, inwiefern irrational („ich muss unbedingt...“) und rational („ich möchte gerne...“) denkenden Stimuluspersonen unterschiedliche Emotionen, Kausalattributionen und Verhaltensweisen zugeschrieben werden. Es zeigt sich, dass adaptive Emotionen bei rational denkenden und maladaptive Emotionen bei irrational denkenden Personen vermutet werden. Hinsichtlich der Dimensionen Stabilität, Lokation und Globalität ergeben sich für irrational im Unterschied zu den rational Denkenden signifikante und konsistente depressogene Attributionsmuster. Zudem wird bei den irrationalen Denkern tendenziell eine stärkere wahrgenommene Kontrollierbarkeit vermutet. Bezüglich zukünftiger Verhaltensweisen werden überwiegend bei rational denkenden Personen produktive Verhaltensresultate vermutet. Zusätzlich erhobene Einschätzungen bestätigen eine höhere Funktionalität adaptiver Emotionen

The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII.

In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas

Charakterisierung des elektrochemischen Mikroanalysesystems ELMAS

Am Forschungszentrum Karlsruhe wurde im Rahmen des Projekts Mikrosystemtechnik das modular aufgebaute elektrochemische Mikroanalysesystem ELMAS unter Verwendung von ISFET-Mikrosensoren und gasfördernden Mikromembranpumpen entwickelt. Der Lösungstransport erfolgt indirekt über die Druckänderungen im Luft- volumen, das sich über der Lösung im Vorratsbehälter befindet. Die pH-ISFETs zeigen ein schnelles Ansprechverhalten und mit Flußraten von 200-300 µl/min sind Zykluszeiten für die Messung und Sensorkalibrierung von 30-60 s realisierbar. Bei Erhöhung der Flußraten sinkt die Zykluszeit, der Lösungsverbrauch hingegen nimmt zu. Für eine Messung sind ca. 50 µl Analyt und maximal 70 µl Kalibrierlösung erforderlich. Aufgrund des Gaspuffers im Vorratsgefäß ist der Fluidstrom gegenüber den Schaltsignalen der Pumpen um 5 s verzögert

A Thermosensitive, Chitosan-Based Hydrogel as Delivery System for Antibacterial Liposomes to Surgical Site Infections

Prophylaxis and the treatment of surgical site infections (SSIs) with antibiotics frequently fail due to the antibiotic resistance of bacteria and the ability of bacteria to reside in biofilms (i.e., bacterial clusters in a protective matrix). Therefore, alternative antibacterial treatments are required to combat biofilm infections. The combination of diethyldithiocarbamate (DDC−) and copper ions (Cu2+) exhibited antibiofilm activity against the staphylococci species associated with SSIs; however, the formation of a water-insoluble Cu(DDC)2 complex limits its application to SSIs. Here, we describe the development and antibiofilm activity of an injectable gel containing a liposomal formulation of Cu(DDC)2 and Cu2+ (lipogel). Lyophilized liposomes were incorporated into a mixture of chitosan (CS) and beta-glycerophosphate (βGP), and the thermosensitive gelling properties of CS-βGP and the lipogel were determined. The liposomes remained stable after lyophilization over six months at 4–6 °C and −20 °C. The sol-gel transition of the gel and lipogel occurred between 33 and 39 °C, independently of sterilization or storage at −20 °C. CS-βGP is biocompatible and the liposomes were released over time. The lipogel prevented biofilm formation over 2 days and killed 98.7% of the methicillin-resistant Staphylococcus aureus and 99.9% of the Staphylococcus epidermidis biofilms. Therefore, the lipogel is a promising new prophylaxis and treatment strategy for local application to SSIs.Laurine Kaul, Clara E. Grundmann, Monika Köll-Weber, Hanna Löffler, Artur Weiz, Andrew C. W. Zannettino, Katharina Richter, and Regine Süs