ChemInform Abstract: A New Naturally‐Occurring Nanoporous Copper Sheet‐Silicate with 6482 Cages Related to Synthetic “CuSH” Phases.

The structure of a new naturally‐occurring nanoporous copper silicate of formula Na₂CaCu₂Si₈O₂₀ ·H₂O is reported and its relations to synthetic nanoporous, so‐called CuSH phases is discussed.     

Using chemical probes to investigate the sub-inhibitory effects of azithromycin

The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.     

Biomimetic total synthesis of malbrancheamide and malbrancheamide B

The biomimetic total syntheses of both malbrancheamide and malbrancheamide B are reported. The synthesis of the two monochloro species enabled the structure of malbrancheamide B to be unambiguously assigned. The syntheses each feature an intramolecular Diels-Alder reaction of a 5-hydroxypyrazin-2(1H)-one to construct the bicyclo[2.2.2]diazaoctane core, which has also been proposed as the biosynthetic route to these compounds.     

Salts of methylated 5-aminotetrazoles with energetic anions

1-methyl-5-aminotetrazole (4, MAT) can easily be protonated by strong acids, yielding known but largely uninvestigated 1-methyl-5-aminotetrazolium nitrate (4a) and perchlorate (4b). Methylation, rather than protonation, of 4 with iodomethane followed by the exchange of the iodide (5a) for nitrate (5b), perchlorate (5c), azide (5d), and dinitramide (5e) yields a new family of energetic methylated aminotetrazole salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray structure determination. Compounds 4a, 4b, and 5c crystallize in the monoclinic space group P2(1)/n, whereas compounds 5b and 5e crystallize in the orthorhombic space group P2(1)2(1)2(1) and 5d in the orthorhombic Fddd. Initial safety testing (impact, friction, and electrostatic sensitivity) and thermal stability measurements (DSC) were also carried out. The MAT salts all exhibit good thermal stabilities (decomposition above 150 degrees C). The constant volume energies of combustion (DeltacU) of 4a, 5b, 5d, and 5e were determined to be -2510(10) cal/g, -3190(30) cal/g, -4500(100) cal/g, and -2570(70) cal/g, respectively, experimentally using oxygen bomb calorimetry. From the experimentally determined density, chemical composition and energies of formation (back calculated from the heats of combustion), the detonation pressures and velocities of 4a (8100 m/s, 25.6 GPa), 5b (7500 m/s, 20.2 GPa), 5d (8200 m/s, 21.7 GPa), and 5e (7500 m/s, 21.2 GPa) were predicted using the EXPLO5 code.     

Carborane Substituents Promote Direct Electrophilic Insertion over Reduction–Metalation Reactions

Two‐electron reduction of 1,1′‐bis(o‐carborane) followed by reaction with [Ru(η‐mes)Cl₂]₂ affords [8‐(1′‐1′,2′‐closo‐C₂B₁₀H₁₁)‐4‐(η‐mes)‐4,1,8‐closo‐RuC₂B₁₀H₁₁]. Subsequent two‐electron reduction of this species and treatment with [Ru(η‐arene)Cl₂]₂ results in the 14‐vertex/12‐vertex species [1‐(η‐mes)‐9‐(1′‐1′,2′‐closo‐C₂B₁₀H₁₁)‐13‐(η‐arene)‐1,13,2,9‐closo‐Ru₂C₂B₁₀H₁₁] by direct electrophilic insertion, promoted by the carborane substituent in the 13‐vertex/12‐vertex precursor. When arene=mesitylene (mes), the diruthenium species is fluxional in solution at room temperature in a process that makes the metal–ligand fragments equivalent. A unique mechanism for this fluxionality is proposed and is shown to be fully consistent with the observed fluxionality or nonfluxionality of a series of previously reported 14‐vertex dicobaltacarboranes.