A First Principles Density Functional Study of Crystalline FOX‐7 Chemical Decomposition Process under External Pressure

We report on a first principles analysis of chemical decomposition reaction in a crystalline FOX‐7 (1,1‐diamino‐2,2‐dinitroethylene) molecule, which is a good candidate for insensitive energetic materials. Our calculations are based on variable‐cell shape methods under pressure, density functional theory with localized numerical orbital and pseudopotential, together with ab initio biasing molecular dynamics. The calculated crystal structure and equation of state (pressure vs. volume) up to 8 GPa agrees well with the corresponding experimental data. A chemical decomposition by intermolecular hydrogen transfer is found at higher pressure. This decomposition appears to be driven by a weakening in the chemical hardness. This suggests that the molecular HOMO and LUMO orbital energy difference is decreased when intermolecular hydrogen transfers occur, and for the FOX‐7 crystal the band gap is narrowed with increasing external pressure.     

Review on the Reactivity of 1,1‐Diamino‐2,2‐dinitroethylene (FOX‐7)

1,1‐Diamino‐2,2‐dinitroethylene (FOX‐7) is a novel high‐energy insensitive material with good thermal stability and low sensitivity, and exhibits excellent application performance in the field of insensitive ammunitions and solid propellant. Although FOX‐7 is simple in molecular composition and structure, its chemical reactivity is abundant and surprising, including salification reaction, coordination reaction, nucleophilic substitution reaction, acetylate reaction, oxidizing reaction, reduction reaction, electrophilic addition reaction, among other reactions. These reactions are systemically summarized and some reaction mechanisms are analyzed in this review.     

Assessment of Tractable Cysteines for Covalent Targeting by Screening Covalent Fragments

Targeted covalent inhibition and the use of irreversible chemical probes are important strategies in chemical biology and drug discovery. To date, the availability and reactivity of cysteine residues amenable for covalent targeting have been evaluated by proteomic and computational tools. Herein, we present a toolbox of fragments containing a 3,5-bis(trifluoromethyl)phenyl core that was equipped with chemically diverse electrophilic warheads showing a range of reactivities. We characterized the library members for their reactivity, aqueous stability and specificity for nucleophilic amino acids. By screening this library against a set of enzymes amenable for covalent inhibition, we showed that this approach experimentally characterized the accessibility and reactivity of targeted cysteines. Interesting covalent fragment hits were obtained for all investigated cysteine-containing enzymes.     

Covalent and Ionic Insensitive High‐Explosives

Ongoing research into new insensitive energetic materials with low sensitivity toward accidental stimuli, high thermal stability and high performance characteristics is undertaken in many research groups worldwide. In order to obtain promising compounds, which fulfil the sensitivity, stability, and performance requirements, researchers use many different strategies. One of the most promising approaches is the synthesis of novel explosives with tailored physico‐chemical properties. In this review the synthesis and properties of some both covalent (NTO, TEX, FOX‐7, ADNP, DNPPs) and ionic (salts of ANDP and DNPP) insensitive explosives are presented, which are of high interest to this field of research.     

Smokeless GAP‐RDX Composite Rocket Propellants Containing Diaminodinitroethylene (FOX‐7)

Composite rocket propellants prepared from nitramine fillers (RDX or HMX), glycidyl azide polymer (GAP) binder and energetic plasticizers are potential substitutes for smokeless double‐base propellants in some rocket motors. In this work, we report GAP‐RDX propellants, wherein the nitramine filler has been partly or wholly replaced by 1,1‐diamino‐2,2‐dinitroethylene (FOX‐7). These smokeless propellants, containing 60% energetic solids and 15% N‐butyl‐2‐nitratoethylnitramine (BuNENA) energetic plasticizer, exhibited markedly reduced shock sensitivity with increasing content of FOX‐7. Conversely, addition of FOX‐7 reduced the thermochemical performance of the propellants, and samples without nitramine underwent unsteady combustion at lower pressures (no burn rate catalyst was added). The mechanical characteristics were quite modest for all propellant samples, and binder‐filler interactions improved slightly with increasing content of FOX‐7. Overall, FOX‐7 remains an attractive, but less than ideal, substitute for nitramines in smokeless GAP propellants.     

Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays

We investigated the reactions between substituted α,β‐unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS‐CoV M^pro) by etacrynic acid derivatives as well as for the excess toxicity of substituted α,β‐unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4‐addition followed by a ketonization step, and underscores the importance of a base‐catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron‐pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s‐cis conformation leads to higher reactivity than the s‐trans conformation. The computed data explain the trends in measured inhibition potencies of substituted α,β‐unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease.     

Directional Interactions of α‐Particles with FOX‐7. A DFT Study

FOX‐7 is exposed to the effects of α‐particles from selected directions of approach. Various energies and properties of these composite FOX‐7 systems (FOX‐7+α‐particle) are obtained. The effect of α‐particles on FOX‐7 is drastic. The CC double bond turns into a single bond and one of the C NO₂ bonds highly elongates. The approach from the side of amino groups results more stable composite system compared to the approach from the side of nitro groups.     

Theoretical Prediction of Heats of Sublimation of Energetic Materials Using Pseudo‐Atomic Orbital Density Functional Theory Calculations

We present a predictive model for the heats of sublimation of the condensed phases of energetic materials that combine the empirical relations of Politzer with first‐principles density‐functional calculations of the electronic properties of the molecular surfaces. The distinct features of our methodology are the use of numerical pseudo‐atomic orbitals for the quantum mechanical calculation of the electronic charge density, as well as an improved technique for the molecular surface area determination. As applications, we used our model to predict heats of sublimation of energetic molecules CL‐20, HMX, RDX, TNT, FOX‐7, TATB, and LLM‐105, with the Politzer parameters fit based on a set of eight nitro‐aromatic molecules. In comparison with conventional quantum chemistry calculations, our approach is tremendously less computationally demanding, yet it still demonstrates competitive accuracy and predictive power.     

CL-20/FOX-7共晶的分子动力学模拟

依据共晶形成的氢键规则,搭建了7种CL-20/1,1-二氨基-2,2-二硝基乙烯(FOX-7)共晶模型;采用分子动力学(MD)模拟研究了CL-20/FOX-7共晶形成的可能性;通过径向分布函数(RDF)考察了共晶模型内分子的相互作用力;采用X-射线粉末衍射(XRD)模拟分析了共晶模型与纯组分间衍射峰的区别。结果表明,FOX-7和CL-20分子间存在较强的氢键和范德华力,7种共晶模型的结合能大小顺序为:Eb(1 0 1)Eb(1 1-1)E_b(随机晶面)E_b(0 1 1)E_b(0 0 2)E_b(1 1 0)E_b(1 0-1);7种共晶模型的分子间作用力以FOX-7取代CL-20(1 0 1)、(11-1)晶面较强;7种共晶模型的XRD衍射峰相较纯组分CL-20或FOX-7区别较大。据此推测在制备CL-20/FOX-7共晶过程中,FOX-7取代CL-20(1 0 1)晶面的共晶模型易于形成。     

Covalent Small Molecules as Enabling Platforms for Drug Discovery

Covalent drugs have experienced significant renewed interest in drug discovery. This resurgence has been accompanied by a better understanding of the reactivity relationships required to engage selective covalent bonds between nucleophilic proteins and electrophilic small molecules. As a result, researchers have come to the realisation that covalent molecules could also represent useful and novel tools aimed at supporting medicinal chemistry programmes. This review surveys the increasing number of drug discovery platforms employing covalent chemistries, and highlights the utility of these techniques for identifying and characterising small molecules and biological targets.     

Addition of Methyl Radical to Substituted Alkenes: A Theoretical Study of the Reaction Mechanism

Ab initio calculations at the QCISD(T)/6–311G^** level have been carried out to study the addition of the methyl radical to a series of substituted alkenes, and the results analyzed with the aid of the curve-crossing model. It is found that (a) reaction exothermicity is the main factor that dominates reactivity, (b) polar contributions to the transition states are generally small and of minor energetic consequences, and (c) the general observation that π-electron-accepting substituents in the alkene enhance reactivity is a secondary correlation that is a consequence of the effect of these substituents on reaction exothermicity. There is no evidence for the prevalent view that the methyl radical is generally nucleophilic towards alkenes.     

Delocalized π‐electrons in 2‐oxazoline rings resulting in negatively charged nitrogen atoms: revealing the selectivity during the initiation of cationic ring‐opening polymerizations

The inventory of the single‐crystal X‐ray structures of aliphatic and aromatic 2‐oxazolines, namely 2‐nonyl‐2‐oxazoline, 2,2′‐tetramethylenebis(2‐oxazoline) and 2‐phenyl‐2‐oxazoline, reveals significant delocalization of π‐electrons along the N? C? O segment. The delocalization of π‐electrons is stabilized by inductive and resonance contributions of the side‐chains; in 2‐phenyl‐2‐oxazoline, also π‐arene interactions between the benzene ring and the C? N and the C? O bond stabilize the crystalline phase. This delocalization gives a partial negative charge to the nitrogen atom and a partial positive charge to the oxygen atom. The partial negative charge of the nitrogen atom makes this atom the exclusive reaction partner also for highly reactive non‐selective cations, which explains the regioselectivity of electrophilic attacks in cationic ring‐opening polymerizations. Copyright © 2011 Society of Chemical Industry     

Ionocovalency and applications 1. Ionocovalency model and orbital hybrid scales

Ionocovalency (IC), a quantitative dual nature of the atom, is defined and correlated with quantum-mechanical potential to describe quantitatively the dual properties of the bond. Orbiotal hybrid IC model scale, IC, and IC electronegativity scale, X(IC), are proposed, wherein the ionicity and the covalent radius are determined by spectroscopy. Being composed of the ionic function I and the covalent function C, the model describes quantitatively the dual properties of bond strengths, charge density and ionic potential. Based on the atomic electron configuration and the various quantum-mechanical built-up dual parameters, the model formed a Dual Method of the multiple-functional prediction, which has much more versatile and exceptional applications than traditional electronegativity scales and molecular properties. Hydrogen has unconventional values of IC and X(IC), lower than that of boron. The IC model can agree fairly well with the data of bond properties and satisfactorily explain chemical observations of elements throughout the Periodic Table.     

Hydrocarbon Selective Oxidation on Vanadium Phosphorus Oxide Catalysts: Insights from Electronic Structure Calculations

The ability of the vanadium phosphorus oxide (VPO) catalyst to selectively activate n-butane and then perform subsequent selective oxidation to maleic anhydride was investigated using electronic structure calculations. Both active site cluster models and periodic surface models, including explicit consideration of surface relaxation and hydration, led to the same qualitative conclusions about the reactivity of the (VO)₂P₂O₇ (1 0 0) surface in substrate adsorption and oxidation. Density functional theory (DFT) reactivity indices and Density of States (DOS) plots show that, whether stoichiometric or phosphorus-enriched, strained or relaxed, bare or hydrated, covalent reactivity at the (1 0 0) surface is controlled by vanadium species, their dual acid–base attack giving selective activation of n-butane via methylene C–H bond cleavage. 1-butene is predicted to chemisorb at the surface using a π-cation complex, the strength of which makes 1-butene an unlikely intermediate in the production of maleic anhydride from n-butane. Coordinatively-unsaturated surface P–O and in-plane P–O–V oxygen species are the most nucleophilic surface oxygens, which may explain the surface-enrichment in phosphorus always seen in industrial catalysts for maleic anhydride synthesis and also recent in situ microscopy images of surface oxygen transfer to n-butane. The resistance of the maleic anhydride selective oxidation product to further transformation was shown to be dependent on its orientation in the active site, and simulation of surface hydration indicated that dissociative adsorption of water may serve to regenerate the catalyst, replenishing its supply of selective nucleophilic oxygen species for mild oxidation.     

Functionalisation of lyocell. Part 1: Amination of lyocell with m-phenylenediaminesulphonic acid derivatives

A series of four colourless, water-soluble agents, based on m -phenylenediaminesulphonic acid, and designed to aminate lyocell, have been synthesised. Each agent carried one or two aromatic amino groups ortho to a water solubilising sulphonic acid group, together with one or two electrophilic groups. The electrophilic groups studied were dichlorotriazinyl, monochlorotriazinyl, vinylsulphonyl and triazinyl betaine. The agents were applied to lyocell by padding techniques, and neutral-exhaustion dyeing of the aminated fibres, with low, medium and high reactivity reactive dyes, in the presence of salt, were performed. Only the high reactivity dichlorotriazinyl dye gave encouraging results. The aminated fabrics, containing aromatic amino groups with an o -sulphonic acid, were insufficiently nucleophilic to allow significant covalent bonding with the low/medium reactivity dyes at both 60 and 80 °C.     

Optimization of Caged Electrophiles for Improved Monitoring of Cysteine Reactivity in Living Cells

Cysteine residues play critical roles in protein function and are susceptible to numerous post‐translational modifications (PTMs) that serve to modulate the activity and localization of diverse proteins. Many of these PTMs are highly transient and labile, thus necessitating methods to study these modifications directly within the context of living cells. We previously reported a caged electrophilic probe, CBK1, that can be activated by UV for temporally controlled covalent modification of cysteine residues in living cells. To improve upon the number of cysteine residues identified in cellular cysteine‐profiling studies, the reactivity and uncaging efficiency of a panel of caged electrophiles were explored. We identified an optimized caged electrophilic probe, CIK4, that affords significantly improved coverage of cellular cysteine residues. The broader proteome coverage afforded by CIK4 renders it a useful tool for the biological investigation of cysteine‐reactivity changes and PTMs directly within living cells and highlights design elements that are critical to optimizing photoactivatable chemical probes for cellular labeling.     

Photofading of azo dyes: a theoretical study

The light fastness of a number of azo dyes has been investigated using all-valence molecular orbital methods, AM1 and PM3. The results of molecular orbital calculations are used to obtain both highest occupied molecular orbital and lowest unoccupied molecular orbital frontier electron density, which, respectively, can account for the propensity of the electrophilic and nucleophilic attack at a particular atom in a molecule. The highest occupied molecular orbital and lowest unoccupied molecular orbital superdelocalisability have also been obtained to explain the order of light fastness values in different dyes of a particular series. In addition, attempts have been made to correlate the light fastness values with the difference in energy of the highest occupied molecular orbital of the dye and the lowest unoccupied molecular orbital of the singlet oxygen.     

溶剂对FOX-7晶体相变和热性能的影响

采用重结晶法在二甲基甲酰胺(DMF)/H2O、二甲基亚砜(DMS)O/H2O和N-甲基吡咯烷酮(NMP)/H2O等不同溶剂体系中得到FOX-7晶体,用扫描电子显微镜(SEM)测试晶体的形貌、变温X-射线粉末衍射(XRD)分析晶型和相变、差示扫描量热仪(DSC)测试其热性能。结果表明,不同溶剂重结晶得到的FOX-7晶体形貌有较大差别,在DMSO/H2O溶剂中得到的晶体质量要优于其他两种;3种溶剂中得到FOX-7晶体的晶型和相变过程相同,即常温下FOX-7的晶型为α晶型,在120℃时,FOX-7完成α→β相变,至185℃时,完成β→γ相变;重结晶的FOX-7晶体5s爆发点温度提高了4~9℃,说明热稳定性增强。     

甲卡西酮光谱性质的密度泛函模拟与指认

采用密度泛函理论的DFT/B3LYP方法和6-311+G(d,p)基组,对甲卡西酮(C10H13NO)的UV-Vis光谱,ECD光谱,IR光谱,拉曼光谱,1HNMR光谱和荧光光谱进行了理论模拟和指认。自然电荷计算表明,胺基N和甲基C原子很可能是其发挥药理活性的亲电和亲核反应中心。     

Understanding the Rate‐Limiting Step of Glycogenolysis by Using QM/MM Calculations on Human Glycogen Phosphorylase

Liver glycogen phosphorylase (GP) is a key enzyme for human health, as its increased activity is associated with type 2 diabetes. The GP catalytic mechanism has been explored by quantum mechanics/molecular mechanics (QM/MM) methods. Herein, we propose a mechanism that proceeds by three steps: 1) it begins with transfer of a hydrogen atom from the phosphate group of the pyridoxal 5′‐phosphate (HPO₄^2?‐PLP) cofactor to the phosphate substrate; 2) the glycosidic linkage is then cleaved through protonation of the glycosidic oxygen atom by a hydroxy group of the inorganic phosphate group; and 3) an oxygen atom of the phosphate performs a nucleophilic attack on the anomeric carbon atom of glucose, concomitant with the return of a proton from phosphate to PO₄^3?‐PLP, which finally leads to formation of the glucose‐1‐phosphate product and recovers the initial state of the PLP cofactor. The glycosidic bond cleavage and nucleophilic attack from the phosphate group to the glycosyl molecule have the highest activation free energies. The structural properties of the hereby characterized transition states could be very useful in structure‐based drug design studies against liver GP.