Chemoenzymatic Asymmetric Synthesis of Pyridine-Based α-Fluorinated Secondary Alcohols

Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.     

Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism

Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M₁-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M₁ positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.     

Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms

Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases.     

A look behind the curtain: Measuring the complex economic effects of regional structural funds in Germany

This paper investigates the mutual impact channels of Germany's major regional policy instrument (GRW) on regional economic development. Different from earlier studies which have predominately focused on a partial assessment of output effects, we explicitly endogenize the factor inputs of the underlying production function. This allows us to comprehensively assess the role of the GRW in driving per capita output, employment, human and physical capital intensities as well as the region's technological growth. The results from a spatial panel vector autoregressive model show that GRW funding has significant positive effects on regional output, the employment rate and human capital intensity.     

Effect of industrial pollution on the distribution of 137Cs in soil and the soil-to-plant transfer in a pine forest in SW Finland

The objective of this study was to evaluate the effect of industrial pollution on the distribution of radiocaesium in soil and on its transfer from soil to plants. The study was started in September 2000 in four Scots pine stands located at distances of 0.5, 2, 4 and 8 km along a transect running SE from the Cu-Ni smelter at Harjavalta in SW Finland. Annual emissions from the smelter in 1990 were 80 t of Cu, 31 t of Ni and 9000 t of SO(2), and in 1999 these were 5.9, 0.8 and 3400 t, respectively. At each site, soil profiles were sampled with a corer, and samples were separated into litter (L), organic soil layer (O) and mineral soil layers (B, E). Mushrooms, lichens (Cladina spp. and Cetraria islandica), lingonberry (Vaccinium vitis-idaea) and crowberry (Empetrum nigrum) plants were collected at each site, except at a distance of 0.5 km, where only mushrooms were available. In the organic soil layer, 137Cs activity decreased from 8000 Bq/m(2) at a distance of 8 km from the smelter to 1500 Bq/m(2) at a distance of 0.5 km; in litter, 137Cs concentration increased from 6300 Bq/m(2) at 8 km to 14000 Bq/m(2) at 0.5 km. 137Cs activity concentration decreased significantly in plants, mushrooms and lichens as the pollution load increased. In lichens, 137Cs activity decreased from 910 Bq/kg at 8 km to 170 Bq/kg at 2 km, while in lingonberry it decreased from 1470 to 20 Bq/kg and in crowberry from 310 to 20 Bq/kg. Aggregated transfer factors for 137Cs decreased in a similar way in lingonberry from 7.6x10(-2) m(2)/kg at 8 km to 7.7x10(-4) m(2)/kg at 2 km and in crowberry from 1.6x10(-2) to 7.9x10(-4) m(2)/kg.     

Flächendatenbank für die hydrogeologische Karte im bayerischen Bodeninformationssystem

The hydrogeological survey of Bavaria has recently been intensified in order to produce a countrywide hydrogeological map at the scale of 1:50,000 by 2015. The spatial data will be seamfree, reflect the 3D-character of hydrogeological maps and comprehensive search functions will be available for the whole dataset. A spatial database was designed which incorporates the complex relations of rock and groundwater bodies. The underlying relational data model integrates the following main object types: propagation of the upper aquifers and surface layers, rock bodies, structural surfaces together with point data and fault lines, groundwater bodies as well as groundwater surfaces together with point data and the distribution of different types of groundwater potential. The database was developed as an ArcGISextension using the Geodatabase as a relational database. The application of this system supports the mapping process and guarantees a consistent data structure. After integration into the Bavarian Soil Information System, the hydrogeological spatial data will be available for the users in a searchable format.