Thin Polymer Films by Oxidative or Reductive Electropolymerization and Their Application in Electrochromic Windows and Thin-Film Sensors.

Electrically conducting and semiconducting polymers represent a special and still very attractive class of functional chromophores, especially due to their unique optical and electronic properties and their broad device application potential. They are potentially suitable as materials for several applications of high future relevance, for example flexible photovoltaic modules, components of displays/screens and batteries, electrochromic windows, or photocatalysts. Therefore, their synthesis and structure elucidation are still intensely investigated. This article will demonstrate the very fruitful interplay of current electropolymerization research and its exploitation for science education issues. Experiments involving the synthesis of conducting polymers and their assembly into functional devices can be used to teach basic chemical and physical principles as well as to motivate students for an innovative and interdisciplinary field of chemistry.

Semisynthetic routes to PF1022H--A precursor for new derivatives of the anthelmintic cyclooctadepsipeptide PF1022A.

The cyclooctadepsipeptide PF1022A and its semisynthetic, commercial analogue emodepside show excellent anthelmintic properties. Bis-hydroxy PF1022 (PF1022H), a minor fermentative side-product represents an interesting precursor for new PF1022 related anthelmintics. We report herein two complementary routes which allow a highly efficient conversion of PF1022A to a regioisomeric mixture consisting mainly of the bis-para isomer PF1022H and the meta-para analogue.

Enantiomerically pure 3-aryl- and 3-hetaryl-2-hydroxypropanoic acids by chemoenzymatic reduction of 2-oxo acids.

Phenyllactic acids are found in numerous natural products as well as in active substances used in medicine or plant protection. Enantiomerically pure phenyllactic acids are available by transition-metal-catalyzed hydrogenations or chemoenzymatic reductions of the corresponding 3-aryl-2-oxopropanoic acids. We show here that d-lactate dehydrogenase from Staphylococcus epidermidis reduces a broad spectrum of 2-oxo acids, which are difficult substrates for transition-metal-catalyzed reactions, with excellent enantioselectivities in a simple experimental setup.

Difluoromethyl ketones: Potent inhibitors of wild type and carbamate-insensitive G119S mutant Anopheles gambiae acetylcholinesterase.

Malaria is a devastating disease in sub-Saharan Africa, and current vector control measures are threatened by emerging resistance mechanisms. With the goal of developing new, selective, resistance-breaking insecticides we explored α-fluorinated methyl ketones as reversible covalent inhibitors of Anopheles gambiae acetylcholinesterase (AgAChE). Trifluoromethyl ketones 5 demonstrated remarkable volatility in microtiter plate assays, but 5c,e-h exhibited potent (1-100 nM) inhibition of wild type (WT) AgAChE and weak inhibition of resistant mutant G119S mutant AgAChE. Fluoromethyl ketones 10c-i exhibited submicromolar to micromolar inhibition of WT AgAChE, but again only weakly inhibited G119S AgAChE. Interestingly, difluoromethyl ketone inhibitors 9c and 9g had single digit nanomolar inhibition of WT AgAChE, and 9g had excellent potency against G119S AgAChE. Approach to steady-state inhibition was quite slow, but after 23 h incubation an IC50 value of 25.1 ± 1.2 nM was measured. We attribute the slow, tight-binding G119S AgAChE inhibition of 9g to a balance of steric size and electrophilicity. However, toxicities of 5g, 9g, and 10g to adult A. gambiae in tarsal contact, fumigation, and injection assays were lower than expected based on WT AgAChE inhibition potency and volatility. Potential toxicity-limiting factors are discussed.

Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity.

The slow delayed rectifier potassium current (IKs ) is formed by the KCNQ1 (Kv 7.1) channel, an ion channel of four α-subunits that modulates KCNE1 ß-subunits. IKs is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac IKs cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates IKs and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved IKs activators as novel therapeutics for the treatment of LQTS.

SeptiFast versus blood culture in clinical routine - A report on 3 years experience.

BACKGROUND: In recent years a multiplex real-time PCR (SeptiFast) has been introduced, allowing detection of 25 common blood pathogens considerably faster than conventional blood culture. METHODS: SeptiFast was applied routinely in addition to blood culture in cases of critically ill patients with fever and other signs of severe systemic infections. In this study data of 470 episodes were retrospectively analysed to assess the impact of various parameters, such as clinical indications, assigning ward and antimicrobial treatment on test outcome using a multivariate logistic model. RESULTS: After exclusion of microorganisms classified as contaminants, the concordance between SeptiFast and blood culture was 85.5%. SeptiFast detected 98 out of 120, while blood culture merely found 63 out of 120 potential pathogens. In comparison to blood culture, SeptiFast showed considerably higher positivity rates in sepsis, pneumonia and febrile immunosuppression and a lower rate in endocarditis. The highest positivity and concordance between tests was shown in patients from the emergency room (P = 0.007). CONCLUSIONS: The results obtained in this study are similar to those from prospective settings confirming the robustness of the SeptiFast assay in routine use. Our data suggest that SeptiFast is a valuable add-on to blood culture and may increase the diagnostic efficiency of a microbiological laboratory.