RESUMEN

Nitrate esters hold pivotal roles in pharmaceuticals, energetic materials, and atmospheric processes, motivating the development of efficient synthesis routes. Here, we present a novel catalytic method for the synthesis of nitrates via the direct O-nitration of alcohols, addressing limitations of current traditional methods. Leveraging bench-stable and recoverable N,6-dinitrosaccharin reagent, our catalytic strategy employs magnesium triflate to achieve mild and selective O-nitration of alcohols, offering broad substrate scope and unprecedentedly large functional group tolerance (e.g. alkenes, alkynes, carbonyls). DFT mechanistic studies reveal a dual role of the magnesium catalyst in the activation of both the nitrating reagent and the alcohol substrate. They also unveil a barrierless proton transfer upon formation of a widely-accepted - yet elusive in solution - nitrooxonium ion intermediate. Overall, our work contributes to the development of mild, selective, and sustainable approaches to nitrates synthesis, with potential applications in drug discovery, materials science, and environmental chemistry.

RESUMEN

A simple and efficient strategy has been developed for the synthesis of organic nitrate esters via visible-light-induced multi-component nitrooxylation reactions of α-diazoesters, cyclic ethers, and tert-butyl nitrite under open air atmosphere. This transformation could be conducted under mild and metal-free conditions to provide a number of organic nitrate esters in moderate to good yields using air as the green oxidant.

RESUMEN

Fluorinated graphene contains F atoms with high levels of chemical activity, and the application of fluorinated graphene in energetic materials may greatly contribute to the progress of combustion reactions. However, there is a lack of research on the thermal properties of fluorinated graphene and its application on nitrate esters. In this paper, theoretical calculations and experiments were used to study the thermal properties of fluorinated graphene and its application on nitrate esters. The anaerobicity and poor thermal stability of fluorinated graphene were proved by ab initio molecular dynamics (AIMD) calculations and TG-DSC experiments. The ester weakening effect of fluorinated graphene on nitroglycerin was determined via wavefunction analysis, with the greater the fluorination degree, the stronger the ester weakening effect. The existence of fluorinated graphene can significantly increase the heat dissipation of the composites, which was concluded by TG-DSC experiments and TG-DSC-MS-FTIR. The research in this article provides an important reference for the application of fluorinated graphene in energetic materials.

RESUMEN

Chagas disease is a health problem that affects millions of persons, currently Nifurtimox (Nfx) and Benznidazole (Bz) are the unique drugs to treat it. However, these drugs produce adverse effects and high toxicity, which has motivated the search for new candidate drugs. Based on reports about the extensive biological activity of steroidal nitrate esters, in this study three nitrate esters steroids (1b, 2b and 4b) were synthetized and characterized from Dehydroepiandrosterone (DHEA, 1a), 19-hydroxy-DHEA (2a), and Androst-5-en-3ß,17ß-diol (4a), respectively. In addition, compounds 3a and 3b were obtained by introducing an α-ethynyl and a ß-hydroxyl groups at position 17 of 2b and further nitration of the hydroxyl group. The trypanocidal activity of these steroids was evaluated in vitro against the epimastigote stage of two T. cruzi strains, Ninoa and TH, and their cytotoxicity over J774.2 macrophage cell line was assayed. Compounds 3a, 3b, and 4a shown higher trypanocidal activity than Bz and Nfx against epimastigotes of Ninoa strain, whereas DHEA (1a) and its nitrate derivative 1b showed higher activity than the reference drugs against the TH strain epimastigote. None of the compounds showed activity in the ex vivo assays against the blood trypomastigote of both strains. Interestingly, the selectivity index of Androst-5-en-3ß,17ß-diol 4a was almost twice the value of Nfx and 50 times more than Bz, against Ninoa and TH strains, respectively. Therefore, compound 4a could represent a valuable starting point toward the optimization of steroid derivatives as trypanocidal agents.

Asunto(s)

Deshidroepiandrosterona/farmacología , Nitratos/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Línea Celular , Deshidroepiandrosterona/síntesis química , Deshidroepiandrosterona/química , Relación Dosis-Respuesta a Droga , México , Ratones , Estructura Molecular , Nitratos/síntesis química , Nitratos/química , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Tripanocidas/síntesis química , Tripanocidas/química

RESUMEN

Xylitol is a polyhydric alcohol that may be nitrated to form an explosive (xylitol pentanitrate or XPN). Consequently, forensic and first response personnel may encounter XPN in post-blast residues or as a bulk material. Despite this, key analytical data for XPN that may be used in first response or forensic operations to aid its detection are not yet available in the literature. The present article provides infrared spectrometry, Raman spectrometry, nuclear magnetic resonance spectrometry, chromatography and mass spectrometry data in order to address this knowledge gap.

RESUMEN

Herein, the synthesis and characterization of a hypervalent-iodine-based reagent that enables a direct and selective nitrooxylation of enolizable C-H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy-to-handle, and delivers the nitrooxy (-ONO2 ) group under mild reaction conditions. Activation of the reagent by Brønsted and Lewis acids was demonstrated in the synthesis of nitrooxylated ß-keto esters, 1,3-diketones, and malonates, while its activity under photoredox catalysis was shown in the synthesis of nitrooxylated oxindoles. Detailed mechanistic studies including pulse radiolysis, Stern-Volmer quenching studies, and UV/Vis spectroelectrochemistry reveal a unique single-electron-transfer (SET)-induced concerted mechanistic pathway not reliant upon generation of the nitrate radical.

RESUMEN

The nitrate esters are important components of double-base propellants. Aromatic amines are recommended as the stabilizers to delay the decomposition of nitrate esters and increase their storage time. The decomposition mechanisms of alkyl, alkoxy dinitrate, and poly-fluoride nitrate esters and the stabilizing effect of aromatic amines including new designed phenols are studied at the level of B3LYP/6-31G**. Alkyl and alkoxyl dinitrate esters are likely to be transformed by hydrogen abstraction, which is consistent with that of mononitrate and trinitrate esters. However, for poly-fluoride nitrate esters, NO2 catalyzed self-decomposition is preferred. In addition, comparing with mononitrate and trinitrate esters, the order of their stability is mononitrates > dinitrates > trinitrates. Poly-fluoride nitrate esters have a poorer stability than non-fluorinated nitrate esters. Comparing with parent nitrate esters, the stability of new designed poly-fluoride oxygen-containing nitrate esters is slightly improved. Aromatic amines including new designed phenols are effective stabilizers of nitrate esters, especially when introduced hydroxyl in the para position, can enhance the effects of stabilizers. The rate constants for the decomposition of nitrate esters and the bimolecular reaction between stabilizers and NO2 are calculated by using traditional transition state theory. Graphical abstractComparison between the reaction energy barrier of nitrate esters and stabilizers with NO2.

RESUMEN

Nitrate esters-based propellant (NEBP) belongs to the main classes of energetic materials being used in civilian and military applications. These NEBPs are not highly stable, and during aging, some of their functional characteristics may change, what can lead to serious safety problems. A thorough analytical characterization of NEBP is of fundamental importance to provide an adequate support for their stability and safe life assessment. Moreover, in order to safely store and fully exploit these energetic materials, accurate analytical techniques and strategies are indispensable to efficiently judge their properties during aging. Although various methodologies have been developed worldwide to evaluate the aging behavior of NEBP, the characterization is not a simple task and often involves the combination of several techniques, whose results have to be evaluated together. This review sought to evaluate existing analytical techniques which can be utilized for a suitable analysis of NEBP stability and aging, evidencing their respective advantages and shortcomings. The employment of each examined technique is described and discussed by relevant examples from the literature.

Asunto(s)

Propelentes de Aerosoles/análisis , Ésteres/análisis , Sustancias Explosivas/análisis , Nitratos/análisis , Cromatografía , Técnicas Electroquímicas , Análisis Espectral

RESUMEN

We compared the effectiveness of different molecular surface electrostatic potential (MESP)-based methods for calculating the density of CHNO explosives. Densities computed for 221 CHNO explosives of different chemical nature and functional groups and compared with the experimental values. The CHNO explosives in this work are divided into seven groups as group I nitrate-esters, group II nitramines, group III azides, group IV energetic materials containing benzene ring, group V energetic materials containing caged and strained rings, group VI energetic materials containing heterocyclic backbone, and group VII are the energetic materials containing fused ring. The computed densities using molecular volume method, Lee method, Kim method, Politzer method, and Rice method judged with experimental data indicates that Politzer and Rice method can be applied for the prediction of density. This study will be useful in selecting an MESP-based approach for the density estimation and directing research efforts towards the development of new CHNO explosives. Graphical Abstract The effectiveness of different molecular surface electrostatic potential (MESP)-based methods such as Lee method, Kim method, Politzer method, and Rice method for calculating the density of 221 CHNO explosives is assessed. The CHNO explosives are divided into seven groups as nitrate-esters, nitramines, azides, energetic materials containing- benzene ring, -caged and strained rings, -heterocyclic backbone, and -fused ring.

RESUMEN

Four heteroaromatic compounds bearing nitrate esters were selected using a virtual-screening procedure as putative sterol 14α-demethylase (CYP51) Candida albicans inhibitors. Compounds were examined for their inhibition on C. albicans growth and biofilm formation as well as for their toxicity. NMR spectroscopy studies, in silico docking, and molecular dynamics simulations were used to investigate further the selectivity of these compounds to fungal CYP51. All compounds exhibited good antimicrobial properties, indicated with low minimal inhibitory concentrations and ability to inhibit formation of fungal biofilm. Moreover, all of the compounds had the ability to inhibit growth of C. albicans cells. N-(2-Nitrooxyethyl)-1Η-indole-2-carboxamide was the only compound with selectivity on C. albicans CYP51 that did not exhibit cytotoxic effect on cells isolated from liver and should be further investigated for selective application in new leads for the treatment of candidiasis.

Asunto(s)

Inhibidores de 14 alfa Desmetilasa/síntesis química , Amidas/síntesis química , Antifúngicos/síntesis química , Candida albicans/enzimología , Ésteres/química , Indoles/síntesis química , Inhibidores de 14 alfa Desmetilasa/farmacología , Inhibidores de 14 alfa Desmetilasa/toxicidad , Amidas/farmacología , Amidas/toxicidad , Animales , Antifúngicos/farmacología , Antifúngicos/toxicidad , Biopelículas/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Ésteres/farmacología , Humanos , Indoles/farmacología , Indoles/toxicidad , Hígado/citología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Unión Proteica , Esterol 14-Desmetilasa/metabolismo , Relación Estructura-Actividad , Porcinos

RESUMEN

The propellants of nitrate esters can be stabilized by some aromatic amines practically. To probe the mechanism of this phenomenon, we performed DFT calculations on: (1) The decompositions of nitrate esters (with and without the catalysis of NO2) and (2) the reaction between the stabilizers and the nitro dioxide (NO2 is released during the storage of nitrate esters). The structures on the reaction paths (reactants, intermediates and products) were optimized at the (U)B3LYP/6-31G** level. It was shown that NO2 lowers the activation energy barrier in the decomposition of nitrate ester by 11.82-17.86kJ/mol and efficiently catalyzes the rupture of ONO2 bond. However, the aromatic amines, typical stabilizers for nitrate esters, can easily eliminate NO2 with activation barriers as low as 27-113kJ/mol (with one exception of 128kJ/mol). These values are, for most cases, lower or much lower than the activation energy barriers for reactions between nitrate esters and NO2 (127-137kJ/mol). Consequently, the stabilizers can block the NO2 catalysis for the decompositions of nitrate esters.

RESUMEN

A mixture of explosives was analyzed by gas chromatography (GC) linked to ultraviolet (UV) spectrophotometry that enabled detection in the range of 178-330 nm. The gas-phase UV spectra of 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), ethylene glycol dinitrate (EGDN), glycerine trinitrate (NG, nitroglycerine), triacetone triperoxide (TATP), and pentaerythritol tetranitrate (PETN) were successfully recorded. The most interesting aspect of the current application is that it enabled simultaneous detection of both the target analyte and its decomposition products. At suitable elevated temperatures of the transfer line between the GC instrument and the UV detector, a partial decomposition was accomplished. Detection was made in real time and resulted in overlaid spectra of the mother compound and its decomposition product. Hence, the presented approach added another level to the qualitative identification of the explosives in comparison with traditional methods that relies only on the detection of the target analyte. As expected, the decomposition product of EGDN, NG, and PETN was NO, while TATP degraded to acetone. DNT and TNT did not exhibit any decomposition at the temperatures used.

RESUMEN

Preclinical Research A new series of 1,3-dimethylxanthine derivatives bearing 8-(2-nitroaryl) residue was synthesized and evaluated for affinity for recombinant human adenosine receptors subtypes. Nitrate esters of 7-substituted-1,3-dimethyl-8-phenylxanthines were also synthesized and tested. Introducing a nitro substituent at the 2-position of the 8-substituted phenyl ring resulted in generally low affinity for adenosine receptors (ARs), selectivity toward the A2A subtype was enhanced in some of the compounds. 8-(4-Cyclopentyloxy-5-methoxy-2-nitrophenyl)-1,3-dimethylxanthine (9e) proved to be a potent compound among the 2-nitrophenyl substituted xanthines exhibiting a Ki = 1 µM at human A2A ARs with at least 30 fold selectivity versus human A1 and A2B ARs. Replacement of 8-chloropropoxy phenyl with 8-nitrooxypropoxy phenyl resulted in a negligible change in binding affinity of the 8-substituted xanthines for various AR subtypes. Drug Dev Res 77 : 241-250, 2016. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2B/metabolismo , Xantinas/metabolismo , Humanos , Ligandos , Unión Proteica , Relación Estructura-Actividad , Xantinas/síntesis química , Xantinas/química

RESUMEN

We have prepared energetic nitrate ester derivatives of 1,2,4,5-tetrazine and 1,2,4-triazolo[4,3-b]-[1,2,4,5]-tetrazine ring systems as model compounds to study the electrochemical behavior of tetrazines in the presence of explosive groups. The model compounds showed lower thermal stabilities relative to PETN (pentaerythritol tetranitrate), but slightly improved mechanical sensitivities. The presence of electron-rich amine donors leads to a cathodic shift of the tetrazine redox potentials relative to those of previously reported tetrazine explosives. At these potentials, electron-rich tetrazines with either covalently bound or co-dissolved nitrate ester groups are irreversibly reduced. Effectively, changes in the electronic structure of tetrazines affect their electrochemical response to the presence of nitrate ester groups. Thus, it may be possible to develop tetrazine-based electrochemical sensors for the detection of specific explosives and electrocatalysts for their disposal.

RESUMEN

This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 °C for the by-products investigated here enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives.