Computer Modeling of Probable Decomposition Reactions: Cyclonitramines

An approach to computer synthesis and retrosynthesis of organic compounds was formulated, and the CASB (Computer-Assisted Structure Building) software for its computer implementation was created. The approach was evaluated by the example of computer generation of probable routes for reactions of homolytic decomposition. Elementary steps of homolysis reactions were modeled with the use of the “retrosynthetic” method. Each elementary reaction describes fragments that should be present in the structure and structural modifications that should be carried out to obtain reaction products. Target fragments are described in terms of production rules by specifying types of atoms, their formal charges and radical states, numbers of adjacent heteroatoms, hybridizations, etc. All possible intermediates of molecular homolysis reactions are generated by the program in a single step and then used in further search for probable pathways of decomposition during subsequent steps until the given maximum number of steps is achieved. Screening of advantageous pathways for these reactions was based on a set of empirical rules. The results obtained by the suggested approach and the corresponding program were illustrated by the example of some cyclic nitramines (RDX and HMX) and demonstrated good agreement with the experiment.     

In situ generation and screening of a dynamic combinatorial carbohydrate library against concanavalin A

Dynamic combinatorial chemistry (DCC) is a recently introduced approach that is based on the generation of combinatorial libraries by reversible interconversion of the library constituents. In this study, the implementation of such libraries on carbohydrate-lectin interactions was examined. The dynamic carbohydrate libraries were generated from a small set (four or six compounds) of initial carbohydrate dimers through mild disulfide interchange, and selection was performed under two conditions defining either adaptive or pre-equilibrated libraries. Upon initiation, libraries were formed that contained comparable amounts of 10 or 21 individual dimeric species, dynamically interchanging during the scrambling process. They were probed with respect to binding to the plant lectin concanavalin A, either present during library generation or added after equilibration. The libraries could be generated easily both in the presence and absence of the receptor, and a bis-mannose structure was preferentially bound and selected from the mixture. Scrambling of the library in the presence of the receptor resulted in slightly higher yields than when the receptor was added after scrambling, indicating that the receptor to some extent acts as a thermodynamic trap during library generation. The present results illustrate the extention of the DCC approach to carbohydrate recognition groups, the generation of isoenergetic dynamic libraries, and the implementation of either adaptive or pre-equilibrated procedures.     

COMBINED CONDUCTION-MIXED CONVECTION-SURFACE RADIATION FROM A UNIFORMLY HEATED VERTICAL PLATE

The present article reports the results of a numerical study on combined conduction-mixed convection-surface radiation from a vertical plate with uniform internal heat generation. The study considers the governing fluid flow and heat transfer equations without boundary layer approximations. Air is taken to be the cooling medium. Stream function-vorticity formulation, coupled with finite volume method, is used to solve the problem. A computer code has been written for the purpose, and results are validated with available experimental and analytical results for asymptotic limiting cases. In addition to making comprehensive parametric studies, useful correlations for evaluating the nondimensional maximum and average temperatures of the plate and mean friction coefficient are deduced based on a large set of data generated from the code.     

Carbon and nitrogen 1s energy levels in amorphous carbon nitride systems: XPS interpretation using first-principles

A series of carbon nitride structures have been generated, by using a classical potential in a Metropolis Monte Carlo liquid quench procedure. The resulting structures are relaxed further using the density functional theory approach. Structures are generated with various mass densities and varying N/C ratios. X-ray photoelectron spectroscopy (XPS) calculations within the first-principles methodology are performed on the generated amorphous carbon nitride systems. Depending on the carbon bonding configuration, the carbon 1s energies are found to vary from 283 to 288 eV while those of nitrogen are found to range from 397 to 405 eV. Additional calculations on model crystalline systems like nitrogen substituted graphite (nitrogen in trigonal structure) and nitrogen substituted diamond support the finding that the C and N 1s energies are not only sensitive to the coordination number of the atom but also to the interatomic distances. Our calculations based on computer generated structures are a viable alternative for the analysis of XPS spectra and support the interpretation of the N 1s energy at 398.4 eV to correspond to two-coordinated N with at least one sp² C nearest neighbor.     

ASTRO‐FOLD 2.0: An enhanced framework for protein structure prediction

The three‐dimensional (3‐D) structure prediction of proteins, given their amino acid sequence, is addressed using the first principles–based approach ASTRO‐FOLD 2.0. The key features presented are: (1) Secondary structure prediction using a novel optimization‐based consensus approach, (2) β‐sheet topology prediction using mixed‐integer linear optimization (MILP), (3) Residue‐to‐residue contact prediction using a high‐resolution distance‐dependent force field and MILP formulation, (4) Tight dihedral angle and distance bound generation for loop residues using dihedral angle clustering and non‐linear optimization (NLP), (5) 3‐D structure prediction using deterministic global optimization, stochastic conformational space annealing, and the full‐atomistic ECEPP/3 potential, (6) Near‐native structure selection using a traveling salesman problem‐based clustering approach, ICON, and (7) Improved bound generation using chemical shifts of subsets of heavy atoms, generated by SPARTA and CS23D. Computational results of ASTRO‐FOLD 2.0 on 47 blind targets of the recently concluded CASP9 experiment are presented. © 2011 American Institute of Chemical Engineers AIChE J, 2012     

Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation

Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment with small compounds, such as epigallocatechin gallate (EGCG) and dopamine (DA), and a loss of fibril shape and decrease in cytotoxicity were observed. However, the characteristics of intermediate products during the fibril disaggregation process are poorly understood. In this study, we found that cytotoxic Aβ aggregates are generated during a moderate disaggregation process of Aβ fibrils. A cytotoxicity assay revealed that Aβ fibrils incubated with a low concentration of EGCG and DA showed higher cytotoxicity than Aβ fibrils alone. Atomic force microscopy imaging and circular dichroism spectrometry showed that short and narrow protofilaments, which were highly stable in the β-sheet structure, were abundant in these moderately disaggregated samples. These results indicate that toxic Aβ protofilaments are generated during disaggregation from amyloid fibrils, suggesting that disaggregation of Aβ fibrils by small compounds may be one of the possible mechanisms for the generation of toxic Aβ aggregates in the brain.     

连续流动系统中颗粒返混与反应率计算的Monte Carlo方法

本文是作者在前文的基础上,应用Monte Carlo方法与“随机树式结构图”,模拟分析了复杂连续流动系统的随机返混、多粒度颗粒的未反应率、以及颗粒反应的动态行为.仿真模拟的物理概念直观、简单,程序简短,在计算机上能容易地完成.对简单情况,其结果与已知方法的结果相吻合.而该问题的确定型方法或Markov模型是由一组复杂的、难于求解的随机微分方程组构成.该方法的应用有可能为计算连续流动反应器内颗粒的行为提供一种可行途径.     

Systematic management and analysis of fatty acid data from multiple tissue samples

A systematic approach has been developed for the collection and analysis of gas chromatographic (GC) data from multiple fatty acid profiles. The approach was applied to a series of polar and nonpolar tissue lipids generated in animal feeding studies to allow a comparison of mean fatty acid profiles as a function of either dietary regimen or tissue location. The magnitude of the studies, sufficiently large to minimize error from animal variabilities, mandated the use of computer assistance. Nevertheless, manual input was essential due to the complexity of the GC patterns, and was invoked for peak assignment and report editing. The approach discussed here allowed for the consolidation and statistical analysis of data from over 30,000 GC peaks, and generated results in both tabular and graphic formats. It should be extendable to other chromatographic studies of lipid components. Agricultural Research Service, U.S. Department of Agriculture, 600 E. Mermaid Lane.     

Photonic efficiency for methanol photooxidation and hydroxyl radical generation on silica-supported TiO2 photocatalysts

Hydroxyl radical species are considered to be responsible for many oxidation pathways of chemical compounds initiated by advanced oxidation technologies and particularly in heterogeneous photocatalytic processes. However, not many attempts have been made to quantify the generation rate of these species for newly developed photocatalysts, especially for the large number of supported photocatalysts synthesized during the last years. This work focuses on the evaluation of the photonic efficiency for the hydroxyl radical generation on several silica-supported TiO₂ photocatalysts recently developed. The study has been carried out by using methanol as hydroxyl radical scavenger. The influence of the mesoporous structure of the support and of its titania loading on the photonic efficiency of the materials has been analyzed. The importance of diffusional restrictions within the porous structure of the support has also been investigated by using a larger hydroxyl radical scavenger molecule, namely n-butanol.     

Transient heating of an insulated slab by non-uniform heat generation

A general, integral equation has been derived for the transient heating of an insulated slab by heat generation that is variable with distance. Two special cases of the general solution are considered:I. Exponential variation of heat generation rate with distance through the slab, andII. Linear variation of heat generation rate with distance through the slab.For these two cases, computer solutions of the equations were obtained and are presented graphically over a wide range of dimensionless variables.     

Spontaneous polarization of polymer blends

A hypothesis on the formation of a non-equilibrium in electrical respect structure in blend compositions induced by generation of free charge carriers and their entrapment during extrusion has been put forward. The electret-thermal analysis (ETA) commonly employed to study electrical polarization of dielectrics has been for the first time used to analyze structures of multicomponent polymer blends. Blend composites turned to have characteristic spectra of thermally stimulated currents (TSC). Potentialities of the ETA have been studied on the polyamide-polyethylene blends containing a compatibilizer—bimodal polyethylene functionalized by maleic anhydride. Peaks on TSC spectra have been identified for each component content and their distribution in the blend. Thermomechanical processing of the studied blends even using specific intensive mixing methods (static and dynamic mixing) did not result in the formation of any new chemical compounds. A conclusion has been derived that the formation of electrically non-equilibrium structure is naturally intrinsic for polymer blend composites.     

Degradation of organophosphorus compounds adsorbed in carbon sorbent pores

A study has been performed on the development of an effective process for exhaustive decomposition of organophosphorus compounds (OPC) via their adsorption in carbon sorbent (CS) pores followed by microwave-induced destruction. It has been found that OPC adsorbed in CS pores with an optimal combination of pore structure and the composition of mineral inclusions undergo fast degradation in the space of sorbent pores during microwave treatment and the mineral components of CSs exhibit a catalytic activity, accelerating the degradation process. It has been shown that the designed process for the effective decomposition of OPC is a fundamentally new approach ensuring the exhaustive detoxification of compounds that pose environmental problems.     

Computer Simulation of Decomposition Mechanisms for CL‐20, Hydrazine,and Their Binary System

An approach to simulate thermal destruction processes of energetic materials has been developed. It is based on the classification of structural features for nitro compounds and the experimental data regarding their decomposition mechanisms. This approach consists of the mathematical simulation of thermal decomposition mechanisms to predict the likely reactions that may occur during the destruction of organic compounds. On the basis of contemporary experimental data on the decomposition of energetic materials from various chemical classes, a set of semi‐empirical rules for modeling possible reaction pathways has been formulated. These rules allow the generation of a whole set of possible decomposition mechanisms for substances at different steps of their destruction. In this study, the suggested methodology is applied to 2,4,6,8,10,12‐hexanitro‐2,4,6,8,10,12‐hexaazaisowurtzitane (CL‐20) and hydrazine and to their binary energetic mixture. It has been shown that thermal decomposition of the binary system consists in decompositions of the separate compounds at the initial stage with subsequent collisions and interactions of the resultant intermediates and decomposition products at different stages. In addition to some experimentally found decomposition products, our simulation showed some other possible compounds among the final products.     

微机励磁系统在硫酸装置余热发电中的应用

励磁调节是发电装置的重要控制设备,随着微电子技术和计算机技术的飞速发展,微机励磁控制在硫酸装置余热发电中得到了应用.介绍其主要功能、特点和在300 kt/a硫磺制酸装置余热发电系统中的配置情况,运行证实该技术投资少、功能全、结构简单、维护方便、运行可靠性高、动态性能指标优良,值得推广.     

Relating the generation of dynamic strain energy to crack propagation in polymers

With many fracture research studies, there is a need to compare frequently experimental findings and modeling simulations. One example is when studying the relationships between crack velocity and dynamic strain energy generated in polymers. It helps in these cases if the same computer can perform the modeling simulations as used to capture and process experimental data. Personal computer (PC)–size machines are often used to capture experimental data, and a fracture simulation model has been devised that can be hosted on a personal computer. In this study, the model is used with the frozen tongue experimental technique to research steady state crack propagation in medium‐density polyethylene (MDPE). This is to study the generation of dynamic strain energy in the material and the factors affecting its availability to the crack tip. This includes the effects of changes in the material's properties immediately about the crack tip, the conditions that determine the threshold to just maintain crack propagation, and the conditions that determine the relationship between crack velocity and strain energy up to the limiting crack velocity.     

Synthesis,Structure–Activity Relationship Studies,and ADMET Properties of 3‐Aminocyclohex‐2‐en‐1‐ones as Chemokine Receptor 2 (CXCR2) Antagonists

Herein we describe the synthesis and structure–activity relationships of 3‐aminocyclohex‐2‐en‐1‐one derivatives as novel chemokine receptor 2 (CXCR2) antagonists. Thirteen out of 44 derivatives were found to inhibit CXCR2 downstream signaling in a Tango assay specific for CXCR2, with IC₅₀ values less than 10 μm . In silico ADMET prediction suggests that all active compounds possess drug‐like properties. None of these compounds show significant cytotoxicity, suggesting their potential application in inflammatory mediated diseases. A structure–activity relationship (SAR) map has been generated to gain better understanding of their binding mechanism to guide further optimization of these new CXCR2 antagonists.     

Covalent Allosteric Inhibitors of Akt Generated Using a Click Fragment Approach

Akt is a protein kinase that has been implicated in the progression of cancerous tumours. A number of covalent allosteric Akt inhibitors are known, and based on these scaffolds, a small library of novel potential covalent allosteric imidazopyridine-based inhibitors was designed. The envisaged compounds were synthesised, with click chemistry enabling a modular approach to a number of the target compounds. The binding modes, potencies and antiproliferative activities of these synthesised compounds were explored, thereby furthering the structure activity relationship knowledge of this class of Akt inhibitors. Three novel covalent inhibitors were identified, exhibiting moderate activity against Akt1 and various cancer cell lines, potentially paving the way for future covalent allosteric inhibitors with improved properties.     

A new technique for the study of reactive species generated during the initial stages of polymer photodegradation

Summary A low temperature ESR technique has been developed for the observation of free radical intermediates generated in clear polymer films during photolysis by UV light under nitrogen. The technique is simple and reproducible, and can be used for polymers having glass transition temperatures at or about room temperature without the need to employ spin traps. The generation of free radicals can be monitored and quantified during exposure, and the radical yields obtained can then be correlated with the chemical structure of the polymer to provide a rapid predictive evaluation of the exterior durability of the polymer.