Controlled release of DNA from photoresponsive hyperbranched polyglycerols with oligoamine shells

Two photo-responsive core/shell nanoparticles based on hyperbranched polyglycerol (hPG) are synthesized for controlled release of DNA. The shell is composed either of bis-(3-aminopropyl)methylamine (AMPA) or pentaethylenehexamine (PEHA) derivatives and is attached to the hPG core with a photo-responsive o-nitrobenzyl linker. Ethidium bromide displacement assay, gel electrophoresis, DLS, and ζ-potential measurements are performed with these nanoparticles. Photo-responsive changes within the carrier scaffold are investigated by irradiating the polymer solution with 350 nm monochromatic light. Fully covered APMA-shelled carriers are found to complex the DNA at an N/P ratio of 10 with an average size ranging from 54 to 78 nm depending on the degree of functionalization of the core.     

Magnesium imide: synthesis and structure determination of an unconventional alkaline earth imide from decomposition of magnesium amide

Magnesium imide (MgNH) was produced by monitoring the decomposition process of magnesium amide with in situ neutron diffraction. Significant changes in the structure of magnesium amide are detected during heat treatment and eventually result in the formation of crystalline MgNH. A model for the crystal structure of magnesium imide (MgNH) is presented for the first time. Remarkably, magnesium imide offers unique structural features similar to the cyclosilicate class and can be described as a porous solid formed by a sequence of linked chains of face sharing Mg(6)N(6) hexagonal prism clusters.     

Roimatacene: an antibiotic against Gram-negative bacteria isolated from Cystobacter ferrugineus Cb G35 (Myxobacteria)

Roimatacene (1) was isolated from the myxobacterium Cystobacter ferrugineus strain Cb G35 in a bioactivity-guided process, by following the antimicrobial activity against Escherichia coli. Since 1 was extremely sensitive to oxygen, a protective isolation and handling protocol was developed, by utilizing the free radical scavenger 4-ethoxyphenol. The structure of 1 was determined by HRMS, 1D and 2D NMR spectroscopy and chemical derivatization to acetonides and Mosher esters to finally establish the absolute configuration. Methionine and acetate were identified as building blocks in the biosynthesis of 1 by feeding experiments with differently (13)C-labeled precursors. The antimicrobial activity of 1 was determined in a broad screening revealing 1 to inhibit several Gram-negative bacteria.     

Powers of tight Hamilton cycles in randomly perturbed hypergraphs

For k ≥ 2 and r ≥ 1 such that k + r ≥ 4, we prove that, for any α > 0, there exists ε > 0 such that the union of an n‐vertex k‐graph with minimum codegree and a binomial random k‐graph with on the same vertex set contains the rth power of a tight Hamilton cycle with high probability. This result for r = 1 was first proved by McDowell and Mycroft.     

Metabolic studies of tetrazepam based on electrochemical simulation in comparison to in vivo and in vitro methods

During the last 2 years, the knowledge on the metabolic pathway of tetrazepam, a muscle relaxant drug, was expanded by the fact that diazepam was identified as a degradation product of tetrazepam. The present study demonstrates that this metabolic conversion, recently discovered by in vivo studies, can also be predicted on the basis of a purely instrumental method, consisting of an electrochemical cell (EC) coupled to online liquid chromatography (LC) and mass spectrometry (MS). By implementing a new electrochemical cell type into the EC-LC–MS set-up and by an enhanced oxidation potential range up to 2 V, one limitation of the electrochemical metabolism simulation, the hydroxylation of alkanes and alkenes, has been overcome. Instead of commonly used flow-through cell with a porous glassy carbon working electrode, a wall-jet cell with exchangeable electrode material was used for this study. Thereby, the entire metabolic pathway of tetrazepam, in particular including the hydroxylation of the tetrazepam cyclohexenyl moiety, was simulated. The electrochemical results were not only compared to microsomal incubations, but also to in vivo experiments, by analysing urine samples from a patient after tetrazepam delivery. For structure elucidation of the detected metabolites, MS/MS experiments were performed. The comparison of electrochemistry to in vitro as well as to in vivo experiments underlines the high potential of electrochemistry as a fast screening tool in the prediction of metabolic transformations in drug development.     

Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

Background

Proteoglycan (PG) in the extracellular matrix (ECM) of the central nervous system (CNS) may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS)-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA) reactivity, a common reagent used to detect "perineuronal nets" (PNNs) of intact matrix and a marker which is thought to label regions of relative neural stability.

Results

WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA.

Conclusion

In general, a marked discordance was observed in the regional localization between WFA and brevican or the ADAMTS-derived N-terminal fragment of brevican. Functionally, this difference may correspond to regions with varied prevalence for neural stability/plasticity.     

Approaching actinide(+III) hydration from first principles

A systematic computational approach to An(III) hydration on a density-functional level of theory, using quasi-relativistic 5f-in-core pseudopotentials and valence-only basis sets for the An(III) subsystems, is presented. Molecular structures, binding energies, hydration energies, and Gibbs free energies of hydration have been calculated for [An(III)(OH(2))(h)](3+) (h = 7, 8, 9) and [An(III)(OH(2))(h-1) * OH(2)](3+) (h = 8, 9), using large (7s6p5d2f1g)/[6s5p4d2f1g] An(III) and cc-pVQZ O and H basis sets within the COSMO implicit solvation model. An(III) preferred primary hydration numbers are found to be 8 for all An(III) at the gradient-corrected density-functional level of theory. Second-order M?ller-Plesset perturbation theory predicts preferred primary hydration numbers of 9 and 8 for Ac(III)-Md(III) and No(III)-Lr(III), respectively.     

Phase separation of methylalumoxane with diethyl ether

After the addition of diethylether to a solution of methylalumoxane in toluene, phase separation can be observed. The investigation of several phase separation experiments led to an idea of the possible composition of methylalumoxane that could be consisting of a basic element and differently associated trimethylaluminium. Investigations of the system methylalumoxane–diethylether–trimethylaluminium show that diethylether is stronger complexed at methylalumoxane than with trimethylaluminium. A second model of the structure of methylalumoxane allows an attempt to explain the phenomenum of phase separation.