Lead Structures for New Antibacterials: Stereocontrolled Synthesis of a Bioactive Muraymycin Analogue

Naturally occurring muraymycin nucleoside antibiotics represent a promising class of novel antibacterial agents. The structural complexity suggests the investigation of simplified analogues as potential lead structures, which can then be further optimized towards highly potent antimicrobials. Herein we report studies on muraymycin‐derived potential lead structures lacking an aminoribose motif found in most naturally occurring muraymycins. We have identified a 5′‐defunctionalized motif to be ideal in terms of stability and chemical accessibility and have synthesized a full‐length muraymycin analogue based on this structure using a novel fully stereocontrolled route. The obtained 5′‐deoxy analogue of the natural product muraymycin C4 showed good inhibitory properties towards the bacterial target protein MraY, sufficient pharmacokinetic stability and no cytotoxicity against human cells, thus making it a promising lead for antibacterial drug development.     

The Elusive Ketene (H2CCO) Channel in the Infrared Multiphoton Dissociation of Solid 1,3,5-Trinitro-1,3,5-Triazinane (RDX)

Understanding of the fundamental mechanisms involved in the decomposition of 1,3,5-trinitro-1,3,5-triazinane (RDX) still represents a major challenge for the energetic materials and physical (organic) chemistry communities mainly because multiple competing dissociation channels are likely involved and previous detection methods of the products are not isomer selective. In this study we exploited a microsecond pulsed infrared laser to decompose thin RDX films at 5 K under mild conditions to limit the fragmentation channels. The subliming decomposition products during the temperature programed desorption phase are detected using isomer selective single photoionization time-of-flight mass spectrometry (PI-ReTOF-MS). This technique enables us to assign a product signal at m/z=42 to ketene (H₂CCO), but not to diazomethane (H₂CNN; 42 amu) as speculated previously. Electronic structure calculations support our experimental observations and unravel the decomposition mechanisms of RDX leading eventually to the elusive ketene (H₂CCO) via an exotic, four-membered ring intermediate. This study highlights the necessity to exploit isomer-selective detection schemes to probe the true decomposition products of nitramine-based energetic materials.     

Highly Efficient Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization

Dynamic nuclear polarization (DNP) is a powerful method to enhance the sensitivity of solid-state magnetic nuclear resonance (ssNMR) spectroscopy. However, its biomolecular applications at high magnetic fields (preferably>14 T) have so far been limited by the intrinsically low efficiency of polarizing agents and sample preparation aspects. Herein, we report a new class of trityl-nitroxide biradicals, dubbed SNAPols that combine high DNP efficiency with greatly enhanced hydrophilicity. SNAPol-1, the best compound in the series, shows DNP enhancement factors at 18.8 T of more than 100 in small molecules and globular proteins and also exhibits strong DNP enhancements in membrane proteins and cellular preparations. By integrating optimal sensitivity and high resolution, we expect widespread applications of this new polarizing agent in high-field DNP/ssNMR spectroscopy, especially for complex biomolecules.     

Noncovalent cross-links in context with other structural and functional elements of proteins

Proteins are heteropolymers with evolutionary selected native sequences of residues. These native sequences code for unique and stable 3D structures indispensable for biochemical activity and for proteolysis resistance, the latter which guarantees an appropriate lifetime for the protein in the protease rich cellular environment. Cross-links between residues close in space but far in the primary structure are required to maintain the folded structure of proteins. Some of these cross-links are covalent, most frequently disulfide bonds, but the majority of the cross-links are sets of cooperative noncovalent long-range interactions. In this paper we focus on special clusters of noncovalent long-range interactions: the Stabilization Centers (SCs). The relation between the SCs and secondary structural elements as well as the relation between SCs and functionally important regions of proteins are presented to show a detailed picture of these clusters, which are believed to be primarily responsible for major aspects of protein stability.     

Steam distillation-solid-phase microextraction for the detection of Ephedra sinica in herbal preparations

A new method involving concurrent solid-phase microextraction combined with continuous hydrodistillation of essential oil was developed. This new methodology allowed for the detection by GC-MS of very small amounts of a diagnostic peak for the authentication of Ephedra sinica, in a short period of time and using only small sample sizes. This diagnostic peak was identified as 4-vinylanisole, and elucidated from the chromatographic profile allowed for the identification of a sample as E. sinica among other species investigated in this study. To the best of our knowledge this is the first report on using continuous solid-phase microextraction coupled to hydrodistillation for the investigation of essential oil components, and the first report of 4-vinylanisole as a marker compound for E. sinica. A total of 46 collections representing 21 species of Ephedra were studied.     

Synthesis and characterization of hyperbranched mesoporous silica SBA-15

Branched mesoporous silica SBA-15 materials have been prepared in a simple process using non-ionic surfactant in acidic conditions in the presence of metal ions.     

Fully transitive -groups with finite first Ulm subgroup

An abelian -group is called (fully) transitive if for all with ( ) there exists an automorphism (endomorphism) of which maps onto . It is a long-standing problem of A. L. S. Corner whether there exist non-transitive but fully transitive -groups with finite first Ulm subgroup. In this paper we restrict ourselves to -groups of type , this is to say -groups satisfying . We show that the answer to Corner's question is no if is finite and is of type .

     

Light-induced degradation of the active layer of polymer-based solar cells

Polymer-based organic solar cells are known to offer a poor stability in real use conditions, and the photodegradation of the active organic layer plays an important role in the reduced lifetime of the devices. This paper focuses on the photodegradation of two conjugated polymers used in organic solar cells, namely poly(2-methoxy-5-(3′,7′-dimethyloctyloxy)-1,4-phenylenevinylene (MDMO-PPV) and poly(3-hexyylthiophene) (P3HT), and their blends with [60]PCBM (methano-fullerene[6,6]-phenyl C61-butyric acid methyl ester), a fullerene derivative. MDMO-PPV and P3HT thin films were submitted to photoageing (λ > 300 nm) in the presence and in the absence of oxygen. The mechanisms by which these polymers degrade were elucidated. P3HT, pristine and blended with PCBM, was shown to be much more stable under illumination than MDMO-PPV. The results showed that, if deposited on an inert substrate and well protected from oxygen with a convenient encapsulation, P3HT:PCBM based active layer should be intrinsically stable for several years in use conditions.