Nitro-tetrazole based high performing explosives:Recent overview of synthesis and energetic properties

Heterocyclic skeleton(Azoles)and different energetic groups containing high performing explosives are highly emerged in recent years to meet the challenging requirements of energetic materials in both military and civilian applications with improved performance.For this purpose tetrazole(Azole)is identified as an attractive heterocyclic backbone with energetic functional groups nitro(-NO_(2)),nitrato(-ONO_(2)),nitrimino(-NNO_(2)),and nitramino(eNHeNO_(2))to replace the traditionally used high performing explosives.The tetrazole based compounds having these energetic functional groups demonstrated advanced energetic performance(detonation velocity and pressure),densities,and heat of formation(HOF)and became a potential replacement of traditional energetic compounds such as RDX.This review presents a summary of the recently reported nitro-tetrazole energetic compounds containing poly-nitro,di/mono-nitro,nitrato/nitramino/nitrimino,bridged/bis/di tetrazole and nitro functional groups,describing their preparation methods,advance energetic properties,and further applications as highperforming explosives,especially those reported in the last decade.This review aims to provide a fresh concept for designing nitro-tetrazole based high performing explosives together with major challenges and perspectives.

Theoretical Study on the Intermolecular Interactions of Tetrazole Dimers

Tetrazole monomers （Ⅰ, Ⅱ） and all of their possible stable dimers （1, 2, 3, 4, 5, 6, 7 and 8） were fully optimized by DFT method at the B3LYP/6-311＋＋G^＊＊ level. Among the eight dimers, there were two 1H-tetrazole dimers, three 2H-tetrazole dimers and three hetero dimers of 1H-tetrazole and 2H-tetrazole. Vibrational frequencies were calculated to ascertain that each structure was stable （no imaginary frequencies）. The basis set superposition errors （BSSE） are 2.78, 2.28, 2.97, 2.75, 2.74, 2.18, 1.23 and 3.10 kJ/mol, and the zero point energy （ZPE） corrections for the interaction energies are 4.88, 4.18, 3.87, 3.65, 3.54, 3.22, 2.87 and 4.34 kJ/mol for 1, 2, 3, 4, 5, 6, 7 and 8, respectively. After BSSE and ZPE corrections, the greatest corrected intermolecular interaction energy of the dimers is -43.71 kJ/mol. The charge redistribution mainly occurs on the adjacent N-H…N atoms between submolecules. The charge transfer between two subsystems is very small. Natural bond orbital （NBO） analysis was performed to reveal the origin of the interaction. Based on the statistical thermodynamic method, the standard thermodynamic functions, heat capacities （C^0P）, entropies （S^0T） and thermal corrections to enthalpy （H^0T）, and the changes of thermodynamic properties from monomer to dimer in the temperature range of 200.00 K to 700 K have been obtained. 1H-tetrazole monomer can spontaneously turn into two stable dimers at 298.15 K.

Synthesis and Characterization of the Tetrazole Analogues of α-Amino Acids

The tetrazole analogues have been synthesized from fluorenylmethoxycarbonyl （Fmoc）- protected amino acids by three steps. The structures of the analogues were characterized by HPLC-MS, ^1H NMR and ^13C NMR.

Coordination Assemblies of Cd^(Ⅱ)with 5-(Ethylthio)-1H-tetrazole and Halide Ions:Synthesis,Structure,and Luminescent Properties

Three cadmium（II）-halide complexes with 5-（ethylthio）-1H-tetrazole（Hett） as ligand, namely [Cd_7Cl_2（ett）_（12）（H_2O）_2]_n（1）, [Cd_2（OH）Br（ett）_2]_n（2） and [Cd_2（OH）I（ett）_2]_n（3）, have been hydrothermally synthesized and characterized. Complex 1 was synthesized at pH = 7 and exhibits a 3D supramolecular framework, where the adjacent Cd ions form a tetrahedron unit by ett ligands bridge and the tetrahedron units share vertices to connect each other by ett bridges to form a 2D layer architecture, which is further interlinked by μ_2-Cl to form 3D structures. Complexes 2 and 3 are isostructural, generated at pH = 8.0~9.0, displaying similar 2D networks via ett ligands and different halide ions（Br-in 2, I-in 3, respectively）. In addition, thermal stabilities and luminescent properties of new complexes 1~3 have been studied.

Syntheses,Crystal Structures and Photoluminescent Properties of Two New 1-D d^10 Metal Complexes Based on Tetrazole 1-Acetato Ligand

Two new tetrazole 1-acetato complexes, [Ag（1-tza）（phen）]∞ （1） and [Cd（1- tza）2（2,2＇-bipy）]∞ （2） （1-Htza = tetrazole 1-acetato, phen = 1,10-phenanthroline, 2,2＇-bipy = 2,2＇-bipyridine）, have been synthesized by solvothermal synthesis and structurally characterized by elemental analyses, IR spectra and single-crystal X-ray diffraction. Complex 1 shows a 1-D chained structure, while the structure of 2 contains two 1-D chains, which is the first 1-tza-based complex containing three different coordination modes of the 1-tza ligand. The aromatic stacking effects play an important role in the formation of supramolecular frameworks of these two complexes. Photoluminescent studies show that the two complexes exhibit efficient luminescence. In addition, optical diffuse reflectance spectra and thermogravimetric analyses of 1 and 2 have also been investigated.

Crystal Structures and Photoluminescence of Two New Tetrazole-based Complexes

The solution reactions of the metal salts with 2,2＇-bipyfidine （2,2＇-bipy） and ethyl tetrazole-5-carboxylate （Hetzc） afforded two new tetrazole-based complexes M（2,2＇-bipy）2（etzc）2 （M=Mn 1, Zn 2）, and their crystal structures were determined by single-crystal X-ray diffraction analyses. Crystallographic data for 1： C28H26MnN12O4, Mr = 649.55, monoclinic, space group C2/c, a= 19.326（15）, b = 11.051（6）, c = 16.388（13）А,β= 117.38（4）° V= 3108（4） А^3, Z= 4, Dc = 1.388 g/cm^3, F（000） = 1340, R = 0.0557 and wR = 0.1269; and those for 2： C28H26ZnN12O4, Mr = 659.98, monoclinic, space group C2/c, a = 19.173（4）, b = 11.006（2）, c = 16.266（4） А, β= 118.11（3）°, V= 3027.4（11） А^3, Z = 4, Dc=1.448 g/cm3, F（000） = 1360, R = 0.0428 and wR = 0.1000. The structures of 1 and 2 are isomorphic and consist of isolated neutral mononuclear units. The metal atoms have highly distorted octahedral coordination environments with two N atoms from two etzc ligands and four N atoms from two 2,2＇-bipy molecules. The isolated mononuclear units are connected by π…π stacking interactions to generate one-dimensional chains. The thermal stability and photoluminescence have also been discussed.

Reaction of Nitrilimines with 2-Aminopicoline, 3-Amino-1,2,4-Triazole, 5-Aminotetrazole and 2-Aminopyrimidine

The reaction of picoline derivatives 3-6 with hydrazonoylhalide 1a produced imidazo[1,2-a]pyridines 7-10, while the reaction of the same picoline derivatives with hydrazonoylhalide 1b afforded imidazo[1,2-a]pyridine-2-ones 11-13. The reaction of 1b, c with 3-amino-1,2,4-triazole 14 produced the acyclic adducts 18 and 19, respectively. Reaction of 1b, 1c with 5-aminotetrazole 20 produced the acyclic products 23 and 24, respectively. Finally, the reaction of 1b with 4, 6-dimethyl-2-aminopyrimidine 27 afforded compound 29 rather than its isomeric structure 28. The structure of the products was confirmed by the different spectroscopic analytical methods including IR, MS, 1HNMR and 13CNMR.

New tetrazole-based organic dyes for dye-sensitized solar cells

A series of new metal-free organic dyes that contain donors with triphenylamine or its derivatives and tetrazole-based acceptors were synthesized and characterized by photophysical, electrochemical, and the- oretical computational methods. They were applied in nanocrystalline TiO2 solar cells （DSSCs）. It is found that the introduction of diphenylamine units as antennas in the as-synthesized dyes could improve photo- voltaic performance compared with phenothiazine and carbazole units as antennas in DSSCs. The dye with （2H-tetrazol-5-yl） acrylonitrile electron acceptor also displayed the highest solar-to-electrical energy conver- sion efficiency.

Electrochemical and Quantum Chemical Studies of 5-Substituted Tetrazoles as Corrosion Inhibitors for Copper in Aerated 0.5 M H₂SO₄Solution

Two 5-substituted tetrazoles, 5-(2-thienyl)-1,2,3,4-tetrazole (2-THTT) and 5-(4-pyridyl)-1,2,3,4-tetrazole (4-PYTT), as copper corrosion inhibitors in aerated 0.5 M H2SO4 solution were studied by using potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and quantum chemical calculation. Polarization curves indicate that inhibition efficiencies of tetrazoles increase with increasing inhibitors concentration. The electrochemical results show that the inhibition efficiency of 2-THTT is higher than that of 4-PYTT. Inhibition efficiency of 2-THTT reached 98.9% at very low concentrations (0.25 mM) by EIS, which makes 2-THTT an efficient inhibitor in aerated 0.5 M H2SO4 solution. The adsorption of 5-substituted tetrazoles on copper surface obeys the Langmuir isotherm. All the computed quantum chemical parameters are found to correlate well with experimental inhibition efficiencies of inhibitors.

Design, Synthesis and Biological Activity of Tetrazole-bearing Uric Acid Transporter 1 Inhibitors

Systematic structure-activity relationship（SAR） exploration of a moderately active tetrazole-bearmg lesinurad-based hit If led to the discovery of a potent uric acid transporter I（URAT1） inhibitor li, which possessed a novel molecular skeleton and was 11-fold more potent than the parent lesinurad against human URAT1 in-vitro （IC50=0.66 gmol/L for li vs. 7.18 μmol/L for lesinurad）.

Synthesis of tetrazole containing 1,2,3-thiadiazole derivatives via U-4CR and their anti-TMV activity

A series of novel tetrazole containing 1,2,3-thiadiazole derivatives were designed and synthesized via Ugi reaction. Their structures were confirmed by melting points, IR, 1H NMR, and HRMS （ESI）. Preliminary bioassay indicated that most target compounds exhibited very good direct anti-TMV activity at 100 μg/mL, which was equal to or higher than that of ribavirin. Among them, compounds 4b, 4c and 4i also showed equivalent protection effect to ribavirin in vivo at 100 μg/mL.

Hydrothermal synthesis method of 5-(4'-methylbiphenyl-2-yl)-1H-tetrazole

A clean and saIe synthesis method of 5-（4＇-methylbiphenyl-2-yl）-1H-tetrazole was round： under hydrothermal conditions, 1.2 equiv, of 4＇-methylbiphenyl-2-carbonitrile react with 1 equiv, of sodium azide in a mixed solvent of propane-1,2-diol/H2O, with 1.5 equiv, of ammonium chloride and 0.2 equiv. of ammonium fluoride as catalyst. After simple post-processing, the yield can be improved to 95%, and the purity of the product is 99% without further recrystaUization.

Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

A novel series of diaryl biuret derivatives containing a tetrazole moiety was designed and synthesized.All the target compounds were evaluated for their in vitro antitumor activity against HT-29,HepG2,MCF-7 and A549 cells by MTT assay.Most of them exhibited obvious antitumor activity,and four of them(4a,4c,4h and 7a)were superior to sorafenib in general.Among them,Compound 4h displayed more potent activity than sorafenib in all tested cancer cells.Compound 4c exhibited the most outstanding activity in inhibition of growth of HepG2 cells(IC50=0.55 μmol/L).Further,they both revealed favorable metabolic stability in in vitro assay.Compounds 4c and 4h are promising candidates for further development.

Decomposition Mechanism of 5,5′-Bis(tetrazole)-1,1′-dioIate(TKX-50) Anion Initiated by Intramolecular Oxygen Transfer

Density functional theory calculations at the B3LYP/6-31+G^** and B3LYP/6-311++G ^** levels were perfonned on thermal decomposition of 5,5′-bis(tetrazole)-1 ,r-diolate(TKX-50) anion with an intramolecular oxygen transfer being an initial step. Tlie results show that the intramolecular oxygen transfers are the rate-limiting steps for the decomposition of title anion with activation energies being in the range of 287-328 kJ/mol. Judged by the nucleus- independent chemical shift values, the formation of antiaromatic ring in transition state or the decrease of aromaticity of the tetrazole ring of the reactant makes somewhat contribution to the high potential energies of the rate-limiting transition states. However, the activation energies of the following N2 elimination tlirough various pathways are in a low range of 136-166 kJ/mol. The tetrazole ring acts as an electron donor or acceptor in difierent pathways to assist the bond nipture or group elimination. The rate constants in a temperature range of 500-2000 K for all the intramolecular oxygen transferring reactions were obtained. The corresponding linear relationships between InA and 1/T were established.

Theoretical study on tetrazole and its derivatives (3) MP2 and thermodynamic calculations of amino derivatives of tetrazole

Fully optimized geometries and electronic structures of amino derivatives of tetrazole are obtained at MP2/6-31G* level. The tetrazole rings are planar and aromatic for all the amino derivatives of tetrazole. The amino group is not co-planar with the ring and its conformation is mainly determined by the lone pair electronic repulsion between the substituents and the ring. N(4) atom is more negatively charged and is the most probable coordination site. The energy gaps between LUMOs and HOMOs of 2H-aminotetrazoles and C-aminotetrazole neutrals are smaller than those of the corresponding 1H-isomers and N-aminotetrazole neutrals respectively. The IR frequencies, thermodynamic properties and temperature-dependent functions for heat capacities in the fom (a + bT + cT2) in the 300–1000K range are reported.

Kv1.5蛋白在内毒素致血管内皮细胞损伤中的作用机制

目的研究Kv1.5蛋白在内毒素致血管内皮细胞损伤中的作用机制。方法体外培养人脐静脉内皮细胞(HUVECs),给予脂多糖(LPS)刺激建立脓毒症模型,并分为:空白对照组、LPS组、LPS+Kv1.5蛋白通道特异性阻滞剂MT1(250nmol/L)组及LPS+MT2(500nmol/L)组,DAPI染色免疫荧光观察各组HUVECs凋亡情况,Western blot检测Caspase-3及Bcl-2蛋白的表达,RT-PCR检测Caspase-3及Bcl-2基因的表达。结果 DAPI染色免疫荧光显示,LPS组内皮细胞核固缩、凋亡小体形成,凋亡小体形成率由空白对照组的(4.2±0.7)%增加至(26.7±0.8)%(P<0.01),而250nmol/L、500nmol/L MT预处理后,凋亡小体形成率从LPS组(26.7±0.8)%分别下降至(12.4±1.0)%、(8.5±0.9)%(均P<0.01);Western blot检测结果显示,LPS组较空白对照组Bcl-2蛋白表达减少、Caspase-3蛋白表达增加(均P<0.01),给予500nmol/L MT预处理后,与LPS组比较,Bcl-2蛋白表达上调、Caspase-3蛋白表达下调(均P<0.01);RT-PCR检测结果显示,LPS组较空白对照组Bcl-2mRNA表达下调、Caspase-3mRNA表达上调(均P<0.01),给予500nmol/L MT预处理后,与LPS组比较,Bcl-2mRNA表达上调、Caspase-3mRNA表达下调(均P<0.01)。结论Kv1.5介导脓毒症相关内皮细胞损伤可能与线粒体凋亡途径有关。

Recent advances on the nitrogen-rich 1,2,4-oxadiazole-azoles-based energetic materials

This review covers recent advances in the synthesis and energetic performance of nitrogen-rich 1,2,4-oxadiazole-azoles-based energetic materials.These materials comprise of 1,2,4-oxadiazole subunit as a key structural motif linked to different nitrogen-rich or nitrogen-oxygen azoles:tetrazole,furazan,furoxan,1,3,4-oxadiazole,pyrazole,and triazole.Particular attention is devoted to the introduction of various energetic groups including nitro,nitramino,azo,azoxy,dinitromethyl,trinitroethyl moieties,and their combination.The physicochemical and available performance parameters including density,decomposition temperature,heat of formation,detonation pressure,detonation velocity,impact sensitivity,and friction sensitivity of typical energetic compounds are also provided and analyzed.Eventually,it was obtained that several screened compounds exhibit superior detonation properties and outstanding insensitivities,which can be classified as a new family of high-performance energetic materials.Additionally,1,2,4-oxadiazole-azoles-based energetic materials still have many thorough works to further exploited and studied,expecting to get very promising insensitive high explosives for practical application and industrialization.

Synthesis, Crystal Structure, and Biological Activity of N-((1-cyclohexyl-1H-tetrazol-5-yl)(5-methyl-1,2,3- thiadiazol-4-yl)methyl)-4-nitrobenzenamine

The title compound N-（（1-cyclohexyl-lH-tetrazol-5-yl）（5-methyl-l,2,3-thiadia- zol-4-yl） methyl）-4-nitrobenzenamine （C17H20N8O2S, Mr = 400.47） was synthesized via Ugi four- components condensation reaction （U-4CR）, and its structure was characterized by IR, aH NMR, high-resolution mass spectrometry and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group Pna21 with a = 20.390（2）, b = 12.9660（14）, c = 6.9399（8） A,β = 90.00°, Z = 4, V= 1834.7（3）A3, Mr = 400.47, Dc = 1.450 g/cm3, μ= 0.210 mm-1, F（000） = 840, R = 0.0348 and wR = 0.0717. X-ray analysis reveals that the dihedral angles formed between the thiadiazole and tetrazole rings, the benzene and tetrazole rings and the thiadiazole and benzene rings are 62.59, 86.73 and 70.07°, respectively. Three intermolecular hydrogen bonds N（1）-H（2）...N（6）, C（4）-H（4B）...O（2） and C（17）-H（17）...N（3） are observed. Bioassay shows that the title compound has antifungal and antivirus activities against tobacco mosaic virus.

Three New Zn(Ⅱ) Coordination Compounds Based on the in-situ Formed Tetrazolate Ligand: Syntheses, Crystal Structures and Luminescence Properties

Reactions of 2-（2-benzoimidazolyl）acetonitrile and Na N3 with Zn SO4 or Zn Cl2 in the presence of nicotinic acid in the mixture of Et OH/H2 O afforded a mononuclear compound [Zn（L1）2]（1） and a 1-D polymer [Zn（L1）Cl]n（2）, respectively（L1 = 5-[（benzoimidazolyl）methyl]-1H-tetrazolate）. However, in the similar condition except that imidazole was added instead of nicotinic acid, the reaction afforded a 1-D compound [Zn（L1）2]n（3） featuring triply helical chains via the π-π stacking of ligands. They are characterized by elemental analysis and IR, and their structures have been determined by X-ray crystallography. Thermal stability of these compounds was measured by TGA and their luminescent properties were investigated at room temperature.

Chemical design and characterization of cellulosic derivatives containing high-nitrogen functional groups:Towards the next generation of energetic biopolymers

In this research,a promising class of insensitive and high-energy dense biopolymers,which contain nitrogen-rich 1H-tetrazol-1-yl acetate and nitrate ester functional groups,was successfully synthesized through tetrazole derivatization and nitration of cellulose and its micro-sized derivative(TNCN and TCMCN).Their molecular structures,physicochemical properties,thermal behaviors,mechanical sensitivities and detonation performances were studied and compared to those of the corresponding nitrocellulose and nitrated micro-sized cellulose(NCN and CMCN).The developed energetic TNCN and TCMCN exhibited insensitive character with excellent features such as density of 1.710 g/cm3and 1.726 g/cm3,nitrogen content of 20.95%and 22.59%,and detonation velocity of 7552 m/s and 7786 m/s,respectively,and thereby demonstrate their potential applications as new generation of energetic biopolymers to substitute the common NCN.Furthermore,thermal results showed that the designed nitrated and chemical modified cellulosic biopolymers displayed good thermal stability with multistep decomposition mechanism.These results enrich future prospects for the design of promising insensitive and high-energy dense cellulose-rich materials and commence a new chapter in this field.