Structural Insights into the Incorporation of the Mo Cofactor into Sulfite Oxidase from Site‐Directed Spin Labeling

Mononuclear molybdoenzymes catalyze a broad range of redox reactions and are highly conserved in all kingdoms of life. This study addresses the question of how the Mo cofactor (Moco) is incorporated into the apo form of human sulfite oxidase (hSO) by using site‐directed spin labeling to determine intramolecular distances in the nanometer range. Comparative measurements of the holo and apo forms of hSO enabled the localization of the corresponding structural changes, which are localized to a short loop (residues 263–273) of the Moco‐containing domain. A flap‐like movement of the loop provides access to the Moco binding‐pocket in the apo form of the protein and explains the earlier studies on the in vitro reconstitution of apo‐hSO with Moco. Remarkably, the loop motif can be found in a variety of structurally similar molybdoenzymes among various organisms, thus suggesting a common mechanism of Moco incorporation.     

Production of the Bengamide Class of Marine Natural Products in Myxobacteria: Biosynthesis and Structure–Activity Relationships

The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half‐life in mice and antitumor efficacy in a melanoma mouse model.     

Snapshot location for POD in control of a linear heat equation

In the present work, we study the approximation of a distributed optimal control problem for a linear heat equation with model order reduction based on Proper Orthogonal Decomposition (POD-MOR). We show that snapshot location for control problems is crucial in model reduction. For the determination of the time instances (snapshot locations) we utilize an a-posteriori error control concept which is based on a reformulation of the optimality system of the underlying optimal control problem as a second order in time and fourth order in space elliptic system. Finally, we present a numerical test to illustrate our approach. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Ball milling in organic synthesis: solutions and challenges

During the last decade numerous protocols have been published using the method of ball milling for synthesis all over the field of organic chemistry. However, compared to other methods leaving their marks on the road to sustainable synthesis (e.g. microwave, ultrasound, ionic liquids) chemistry in ball mills is rather underrepresented in the knowledge of organic chemists. Especially, in the last three years the interest in this technique raised continuously, culminating in several high-quality synthetic procedures covering the whole range of organic synthesis. Thus, the present tutorial review will be focused on the highlights using this method of energy transfer and energy dissipation. The central aim is to motivate researchers to take notice of ball mills as chemical reactors, implementing this technique in everyday laboratory use and thus, pave the ground for future activities in this interdisciplinary field of research.     

Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion

In the current study Ibuprofen was embedded in a methacrylate copolymer (Eudragit^® EPO) matrix to produce solid dispersions by hot-melt extrusion (HME) processing. The obtained granules were incorporated in orally disintegrating tablets (ODTs). The tablets were developed by varying the ratio of superdisintegrants such as sodium croscarmellose and crosslinked polyvinylpyrrolidone grades while a direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets which included porosity, hardness, friability and dissolution profiles were further evaluated and compared with Nurofen^® Meltlet ODTs. The taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and improved tablet palatability.     

Rapid identification and semi-quantitative determination of polymer additives by desorption electrospray ionization/time-of-flight mass spectrometry

A fast and simple method for the direct qualitative and semi-quantitative determination of a set of four polymer additives in plastic samples by desorption electrospray ionization time-of-flight mass spectrometry (DESI-TOF-MS) is presented. After evaluation of crucial DESI parameters such as composition of spray solutions and spray voltages, a series of lab-made polypropylene samples containing Chimassorb 81 (2-hydroxy-4-n-octoxybenzophenone), Tinuvin 328 (2-(2-hydroxy-3, 5-ditert-pentylphenyl)-benzotriazole), Tinuvin 326 (2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chloro benzotriazole), and Tinuvin 770 (bis(2,2,6,6,-tetramethyl-4-piperidyl)sebaceate) in concentrations between 0.02% and 0.2% were analyzed, resulting in calibration graphs with R ² better than 0.994. To demonstrate the applicability of the developed method for the investigation of real samples, liners for in-ground swimming pools and polypropylene granules were analyzed with respect to their content in the selected polymer additives. Two alternative methods, both well established in the fields of polymer additive analysis, namely HPLC with UV detection (after previous extraction) and thermodesorption gas chromatography/mass spectrometry have been employed for evaluation of the results from the DESI experiments.