An Alliance of Polynitrogen Heterocycles: Novel Energetic Tetrazinedioxide-Hydroxytetrazole-Based Materials.

Energetic materials constitute one of the most important subtypes of functional materials used for various applications. A promising approach for the construction of novel thermally stable high-energy materials is based on an assembly of polynitrogen biheterocyclic scaffolds. Herein, we report on the design and synthesis of a new series of high-nitrogen energetic salts comprising the C-C linked 6-aminotetrazinedioxide and hydroxytetrazole frameworks. Synthesized materials were thoroughly characterized by IR and multinuclear NMR spectroscopy, elemental analysis, single-crystal X-ray diffraction and differential scanning calorimetry. As a result of a vast amount of the formed intra- and intermolecular hydrogen bonds, prepared ammonium and amino-1,2,4-triazolium salts are thermally stable and have good densities of 1.75-1.78 g·cm-3. All synthesized compounds show high detonation performance, reaching that of benchmark RDX. At the same time, as compared to RDX, investigated salts are less friction sensitive due to the formed net of hydrogen bonds. Overall, reported functional materials represent a novel perspective subclass of secondary explosives and unveil further opportunities for an assembly of biheterocyclic next-generation energetic materials.

Nitro-, Cyano-, and Methylfuroxans, and Their Bis-Derivatives: From Green Primary to Melt-Cast Explosives.

In the present work, we studied in detail the thermochemistry, thermal stability, mechanical sensitivity, and detonation performance for 20 nitro-, cyano-, and methyl derivatives of 1,2,5-oxadiazole-2-oxide (furoxan), along with their bis-derivatives. For all species studied, we also determined the reliable values of the gas-phase formation enthalpies using highly accurate multilevel procedures W2-F12 and/or W1-F12 in conjunction with the atomization energy approach and isodesmic reactions with the domain-based local pair natural orbital (DLPNO) modifications of the coupled-cluster techniques. Apart from this, we proposed reliable benchmark values of the formation enthalpies of furoxan and a number of its (azo)bis-derivatives. Additionally, we reported the previously unknown crystal structure of 3-cyano-4-nitrofuroxan. Among the monocyclic compounds, 3-nitro-4-cyclopropyl and dicyano derivatives of furoxan outperformed trinitrotoluene, a benchmark melt-cast explosive, exhibited decent thermal stability (decomposition temperature >200 °C) and insensitivity to mechanical stimuli while having notable volatility and low melting points. In turn, 4,4'-azobis-dicarbamoyl furoxan is proposed as a substitute of pentaerythritol tetranitrate, a benchmark brisant high explosive. Finally, the application prospects of 3,3'-azobis-dinitro furoxan, one of the most powerful energetic materials synthesized up to date, are limited due to the tremendously high mechanical sensitivity of this compound. Overall, the investigated derivatives of furoxan comprise multipurpose green energetic materials, including primary, secondary, melt-cast, low-sensitive explosives, and an energetic liquid.

Direct Synthesis of N-(1,2,5-Oxadiazolyl)hydrazones through a Diazotization/Reduction/Condensation Cascade.

A straightforward synthesis of a series of previously unknown N-(1,2,5-oxadiazolyl)hydrazones through the diazotization/reduction/condensation cascade of amino-1,2,5-oxadiazoles was accomplished. The described protocol was suitable for a wide array of target hydrazones, which were prepared in good to high yields under smooth reaction conditions with very good functional group tolerance. Importantly, the presented approach unveils a direct route to in situ generation of previously inaccessible (1,2,5-oxadiazolyl)hydrazines. In addition, a first example of the ionic structure incorporating a protonated hydrazone motif linked to the 1,2,5-oxadiazole 2-oxide subunit was synthesized, indicating the stability of prepared compounds toward acid-promoted hydrolysis. Overall, this method provides a direct access to the isosteric analogues of drug candidates for treatment of various neglected diseases, thus enabling their potential application in medicinal chemistry and drug design.

Straightforward Access to the Nitric Oxide Donor Azasydnone Scaffold by Cascade Reactions of Amines.

A novel one-pot cascade method for the assembly of valuable NO-donor azasydnone scaffold has been developed. The construction strategy involves a diazotization/azo coupling/elimination/double rearrangement cascade sequence of readily available amines. The current protocol enables the generation of a diverse array of azasydnones, including previously hardly accessible heteroaryl substituted azasydnones (25 examples, 70-97 % yield) with a good functional group tolerance under very mild conditions. Preliminary NO-releasing studies revealed an ability of azasydnones to produce NO in a wide range of concentrations. This method provides a new approach to nitrogen-oxygen heterocycles with potential applications in medicine and material science.

Nanodiamond-chymotrypsin and nanodiamond-papain conjugates, their synthesis and activity and visualization of their interaction with cells using optical and electron microscopy.

Two novel conjugates of detonation nanodiamonds (dNDs) with the proteolytic enzymes chymotrypsin and papain were synthesized. The synthesis was performed via functionalization of the dNDs' surface with acidic/alkali treatment followed by carbodiimide-mediated protein binding. Covalent binding of the enzymes was confirmed by Fourier transform infrared spectrographic analysis and high-performance liquid chromatography (HPLC) amino acid analysis. HPLC also proved the preservation of the enzymes' composition during synthesis. The same assay was used to determine the binding ratios. The ratios were 12% (mass to mass) for chymotrypsin and 7.4% for papain. The enzymatic activity of the conjugates was measured using chromogenic substrates and appeared to be approximately 40% of that of the native enzymes. The optimum pH values and stability under various conditions were determined. The sizes of resulting particles were measured using dynamic light scattering and direct electron microscopic observation. The enzyme conjugates were shown to be prone to aggregation, resulting in micrometer-sized particles. The ζ-potentials were measured and found to be positive for the conjugates. The conjugated enzymes were tested for biological activity using an in vitro model of cultured transformed human epithelial cells (HeLa cell line). It was shown that dND-conjugated enzymes effectively bind to the surface of the cells and that enzymes attack exposed proteins on the plasma membrane, including cell adhesion molecules. Incubation with conjugated enzymes results in morphological changes of the cells but does not affect cell viability, as judged by monitoring the cell division index and conducting ultrastructural studies. dNDs are internalized by the cells via endocytosis, being enclosed in forming coated vesicles by chance, and they accumulate in single membrane-bound vacuoles, presumably late endosomes/phagosomes, along with multimembranous onionlike structures. The authors propose a model of a stepwise conjugate binding to the cell membrane and gradual release of the enzymes.