Mechanistic insights into neurotoxicity induced by anesthetics in the developing brain

Compelling evidence has shown that exposure to anesthetics used in the clinic can cause neurodegeneration in the mammalian developing brain, but the basis of this is not clear. Neurotoxicity induced by exposure to anesthestics in early life involves neuroapoptosis and impairment of neurodevelopmental processes such as neurogenesis, synaptogenesis and immature glial development. These effects may subsequently contribute to behavior abnormalities in later life. In this paper, we reviewed the possible mechanisms of anesthetic-induced neurotoxicity based on new in vitro and in vivo findings. Also, we discussed ways to protect against anesthetic-induced neurotoxicity and their implications for exploring cellular and molecular mechanisms of neuroprotection. These findings help in improving our understanding of developmental neurotoxicology and in avoiding adverse neurological outcomes in anesthesia practice.     

钛硅分子筛TS-1催化环氧丙烷异构反应的机理探究

丙烯氢氧环氧化一步法制备环氧丙烷（PO）相比于传统的PO工业生产方法在经济和环保方面具有不可比拟的优势。Au/TS-1双功能催化剂在该反应中展现出较优的PO性能,针对其中TS-1催化PO开环异构生成副产物进行了研究,结合PO在堵孔TS-1分子筛（TS-1-B）和Au/TS-1-B催化剂上的反应性能和红外表征结果,采用理论计算探究了Ti-Defect位点上丙醛和丙酮的生成路径以及涉及的能量变化。结果显示PO在TS-1上的异构化主要经历碳氧键断裂和氢原子转移重排两个过渡态,以及具有五元环结构的双配位丙氧基物种中间体。相比于丙醛,丙酮由于生成过程中氢原子重排的过渡态能垒较高而具有更低的异构化选择性。所揭示的TS-1上PO吸附及异构化反应机制将为钛基丙烯环氧化催化剂的结构改性以增强PO脱附从而提高PO选择性提供理论依据。     

Mechanistic insights into homogeneous electrocatalytic reaction for energy storage using finite element simulation

The application of homogeneous electrocatalytic reactions in energy storage and conversion has driven surging interests of researchers in exploring the reaction mechanisms of molecular catalysts. In this paper, homogeneous electrocatalytic reaction between hydroxymethylferrocene (HMF) and L-cysteine is intensively investigated by cyclic voltammetry and square wave voltammetry for which, the second-order rate constant (k_ec) of the chemical reaction between HMF⁺ and L-cysteine is determined via a 1D homogeneous electrocatalytic reaction model based on finite element simulation. The corresponding k_ec (1.1 (mol·m^-3)^-1·s^-1) is further verified by linear sweep voltammograms under the same model. Square wave voltammetry parameters including potential frequency (f), increment (E_step) and amplitude (E_SW) have been comprehensively investigated in terms of the voltammetric waveform transition of homogeneous electrocatalytic reaction. Specifically, the effect of potential frequency and increment is in accordance with the potential scan rate in cyclic voltammetry and the increase of pulsed potential amplitude results in a conspicuous split oxidative peaks phenomenon. Moreover, the proposed methodology of k_ec prediction is examined by hydroxyethylferrocene (HEF) and L-cysteine. The present work facilitates the understanding of homogeneous electrocatalytic reaction for energy storage purpose, especially in terms of electrochemical kinetics extraction and flow battery design.     

Mechanistic insights into the structure‐dependent selectivity of catalytic furfural conversion on platinum catalysts

The effects of surface structures on the selectivity of catalytic furfural conversion over platinum (Pt) catalysts in the presence of hydrogen have been studied using first principles density functional theory (DFT) calculations and microkinetic modeling. Three Pt model surface structures, that is, flat Pt(111), stepped Pt(211), and Pt₅₅ cluster are chosen to represent the terrace, step, and corner sites of Pt nanoparticle. DFT results show that the dominant reaction route (hydrogenation or decarbonylation) in furfural conversion depends strongly on the structures (or reactive sites). Using the size‐dependent site distribution rule, our microkinetic modeling results indicate the decarbonylation route prevails over smaller Pt particles less than 1.4 nm while the hydrogenation is the dominant reaction route over larger Pt catalyst particles at T = 473 K and = 93 kPa. This is in good agreement with the reported experimental observations. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3812–3824, 2015     

Mechanistic insights into aqueous phase propanol dehydration in H‐ZSM‐5 zeolite

Aqueous phase dehydration of 1‐propanol over H‐ZSM‐5 zeolite was investigated using density functional theory (DFT) calculations. The water molecules in the zeolite pores prefer to aggregate via the hydrogen bonding network and be protonated at the Brønsted acidic sites (BAS). Two typical configurations, i.e., dispersed and clustered, of water molecules were identified by ab initio molecular dynamics simulations of the mimicking aqueous phase H‐ZSM‐5 unit cell with 20 water molecules per unit cell. DFT calculated Gibbs free energies suggest that the dimeric propanol–propanol, the propanol–water, and the trimeric propanol–propanol–water complexes are formed at high propanol concentrations in aqueous phase, which provide a kinetically feasible dehydration reaction channel of 1‐propanol to propene. The calculation results indicate that the propanol dehydration via the unimolecular mechanism becomes kinetically discouraged due to the enhanced stability of the protonated dimeric propanol and the protonated water cluster acting as the BAS site for alcohol dehydration. © 2016 American Institute of Chemical Engineers AIChE J, 63: 172–184, 2017     

Mechanistic insights into the selective hydrogenation of resorcinol to 1,3-cyclohexanedione over Pd/rGO catalyst through DFT calculation

In our previous work, graphene-supported Pd catalyst (Pd/rGO) exhibited higher activity and selectivity for the liquid phase selective hydrogenation of resorcinol to 1,3-cyclohexanedione compared with other catalysts. In the present study, further experimental and theoretical investigations were conducted to reveal the reaction mechanism and the catalytic mechanism of Pd/rGO for resorcinol hydrogenation. The effects of graphene nanosheet and the solvent on the reaction were investigated, and the pathway for resorcinol hydrogenation was proposed supported by density functional theory (DFT) calculations. The results showed that the excellent selectivity of Pd/rGO to 1,3-cyclohexanedione was attributed to the strong π–π and p–π interactions between the graphene nanosheet and the benzene ring as well as hydroxyl in resorcinol molecule, which was in agreement with our previous speculation. In weak polar aprotic solvents, solvation free energy had less impact to the π–π and p–π interactions mentioned above. In strong polar aprotic solvents and polar protic solvents, however, the influence of solvation free energy was much greater, which led to the decrease in the conversion of resorcinol and the selectivity to 1,3-cyclohexanedione.     

Mechanistic insight into the methanol-to-hydrocarbons reaction

For nearly 30 years, it has been known that methanol may be converted to a mixture of hydrocarbons and water over protonated zeolites. During this time, a large amount of work has been carried out to obtain an understanding of the reaction mechanism involved [C.D. Chang, Catal. Rev. 25 (1983) 1; M. Stöcker, Micropor. Mesopor. Mater. 29 (1999) 3; C.D. Chang, Shape-selective catalysis: chemicals synthesis and hydrocarbon processing, in: C. Song, J.M. Garcés, Y. Sugi, (Eds.), ACS Symposium Series, vol. 738, Washington, DC, 2000; J.F. Haw, Phys. Chem. Chem. Phys. 4 (2002) 5431; J.F. Haw, W. Song, D.M. Marcus, J.B. Nicholas, Acc. Chem. Res. 36 (5) (2003) 317]. We here aim at presenting some major contributions to today's rather unified view on the MTH reaction mechanism, and, based on this detailed knowledge, to point at possible options for optimizing the performance of MTH catalysts.     

Reactive alloy melt infiltration for SiC composite matrices: Mechanistic insights

A comparative study of reactive melt infiltration using Si and Si‐Y alloys is presented to provide insight into the governing processes that control the effectiveness of the melt interaction with a carbonaceous preform and the temperature capability of the SiC matrix for ceramic matrix composites. Through experiments on two substantially different scales of capillaries in porous graphite tubes using Si and Si‐Y alloys, the current study has characterized the phenomena that play a role in the infiltration of the melt and its reaction with the preform. It is shown that (i) the interface reaction controls wetting in both large and small capillaries and the climb rate is enhanced by the presence of Y; (ii) reaction choking occurs at critical throats within the pore network, usually behind the infiltration front; and (iii) different residual silicides can form during reaction and upon cooling. A potential mechanism for SiC growth is described, and the implications for the interplay between SiC growth and infiltration are discussed.     

Mechanistic Insight into Permeation of Plasma-Generated Species from Vacuum into Water Bulk

Due to their potential benefits, cold atmospheric plasmas (CAPs), as biotechnological tools, have been used for various purposes, especially in medical and agricultural applications. The main effect of CAP is associated with reactive oxygen and nitrogen species (RONS). In order to deliver these RONS to the target, direct or indirect treatment approaches have been employed. The indirect method is put into practice via plasma-activated water (PAW). Despite many studies being available in the field, the permeation mechanisms of RONS into water at the molecular level still remain elusive. Here, we performed molecular dynamics simulations to study the permeation of RONS from vacuum into the water interface and bulk. The calculated free energy profiles unravel the most favourable accumulation positions of RONS. Our results, therefore, provide fundamental insights into PAW and RONS chemistry to increase the efficiency of PAW in biological applications.     

NMR analysis of cbEGF domains gives new insights into the structural consequences of a P1148A substitution in fibrillin-1

Fibrillin-1 is a modular glycoprotein and a major component of the 10- 12nm microfibrils of the extracellular matrix. Mutations in the fibrillin-1(FBN 1) gene result in the connective tissue disease the Marfan syndrome(MFS) and related disorders. The calcium binding EGF- like (cbEGF) domainis the predominant structural motif of the protein and >70% of mutationsleading to MFS disrupt this domain. A missense mutation which changes aproline to alanine (P1148A) in cbEGF domain 13 has been associated with anumber of fibrillin disorders including MFS and Shprintzen-Goldbergsyndrome. However, it has also been described as a polymorphism. In thisstudy comparative NMR analyses on wild-type and mutant forms ofcovalently-linked fibrillin cbEGF domain pairs have been performed toinvestigate the structural consequences of this substitution. A comparisonof the two-dimensional NOESY spectra of the wild-type and mutant forms ofcbEGF domains 12 & 13 and cbEGF domains 13 & 14 indicated that theproline to alanine amino acid change does not introduce a significantstructural defect into cbEGF domain 13 or the adjacent domains and mostlikely represents a polymorphism. These results demonstrate how, in thecase of a protein with a well defined domain organisation such asfibrillin-1, comparative NMR analyses can be used to substantiate geneticevidence for the polymorphic status of an amino acid.     

Catalysis and mechanistic insights into sirtuin activation

SIRT1 is a member of the Sir2 family of NAD(+)-dependent protein deacetylases. The central role of SIRT1 in multiple metabolic and age-related pathways has pushed SIRT1 to the forefront to discover small-molecule activators. Promising compounds, including resveratrol and SRT1720 have been reported, however, whether these compounds are direct activators and the mechanism by which they activate remains poorly defined. This review examines the current debate surrounding purported activators, and will focus on the assays used in screening compounds, sirtuin catalysis, and the mechanistic basis for their actions. We discuss the potential pathways of SIRT1 activation that could be exploited for the development of novel therapeutics for treating type II diabetes, neurodegeneration, and diseases associated with aging.     

New insights into dye chemistry and physics

A review of the academic dye research performed by the Port Sunlight group and its coworkers over the past 15 years is presented. The work is focused on three areas: (1) substrate structure; (2) dye interactions in aqueous solution and on substrates; (3) dye degradation and products. For substrates, a detailed model of the nanoenvironment experienced by chemicals within cellulose fibre is given, showing the different environments and remarkable mobility of absorbed chemicals. Advanced nuclear magnetic resonance diffusion measurements provide the complex pathways by which compounds find their way in and out of the fibre. For dye interaction, detailed theoretical and experimental studies are reported on three model dye systems, the anionic monoazo dye Orange II, the bisazo anionic dye CI Direct Blue 1, and cationic monoazo thiazolium dyes, providing a comprehensive picture of their structure. A quantitative mechanism of dye binding to cellulose is shown. Resonance Raman provides an effective forensic tool for dye identification, even from single fibres. The products and kinetics of Orange II dye degradation by one‐electron reduction in aqueous solution is given, with the identification of an indophenol dye end‐product. In cellulosic materials the reduction mechanism is similar to solution, when the higher microviscosity is accounted for. Hydrolysis of thiazolium dyes occurs at both aromatic rings of the dye but on different timescales. Measurement and calculations of the electronic structures of one‐electron‐reduced and ‐oxidised dyes are presented. The mechanism of photooxidation by sunlight of azo dyes in cotton is delineated.     

Novel insights into siderophore formation in myxobacteria

The myxochelins are catecholate-type siderophores produced by a number of myxobacterial strains, and their corresponding biosynthetic gene clusters have been identified in Stigmatella aurantiaca Sg a15, and Sorangium cellulosum So ce56; the latter being presented in this work. Biochemical and genetic studies described here further clarify myxochelin biosynthesis. In addition to the myxochelin A biosynthetic complex, the aminotransferase MxcL is required in order to form myxochelin B, starting from 2,3-dihydroxy benzoic acid and L-lysine. Additionally, the substrate specificity of the myxochelin A biosynthetic complex was analyzed in vitro; this led to the formation of novel myxochelin derivatives. Furthermore, MxcD was over-expressed and its function as an active isochorismic acid synthase in Escherichia coli was verified by complementation studies, as was activity in vitro. The organization of the myxochelin gene cluster of S. cellulosum So ce56 was compared to that of the Sg a15 gene cluster. The comparison revealed that although the organization of the biosynthetic genes is completely different, the biosynthesis is most probably extremely similar.     

Mechanistic Insights into the Link between Obesity and Prostate Cancer

Obesity is a pandemic of increasing worldwide prevalence. There is evidence of an association between obesity and the risk of prostate cancer from observational studies, and different biologic mechanisms have been proposed. The chronic low-level inflammation within the adipose tissue in obesity results in oxidative stress, activation of inflammatory cytokines, deregulation of adipokines signaling, and increased circulating levels of insulin and insulin-like growth factors (IGF). These mechanisms may be involved in epithelial to mesenchymal transformation into a malignant phenotype that promotes invasiveness, aggressiveness, and metastatic potential of prostate cancer. A thorough understanding of these mechanisms may be valuable in the development of effective prostate cancer prevention strategies and treatments. This review provides an overview of these mechanisms.     

Mechanistic Studies into Metal‐Catalyzed Aldoxime to Amide Rearrangements

The metal‐catalyzed rearrangement of aldoximes into primary amides is a completely atom economical synthetic method for the preparation of one of the most important functional groups in chemistry. There have been several reports of various metals successfully catalyzing this reaction, however, there are conflicting views as to the mechanism involved. Herein we report new experimental evidence to support the mechanism and whether this is universal to all catalysts reported or metal specific. We also describe our further studies into the mechanism of the nickel‐catalyzed acylation of amines with aldoximes.     

New insights into rubber-clay nanocomposites by AFM imaging

In the present study, topographic and phase imaging in tapping mode atomic force microscopy was performed to investigate the size of clay platelets, the polymer-filler interface, pull-off and contact forces between the sample and the tip, power spectral density, fractal dimension and spatial distribution of the nanoclays [unmodified (Cloisite NA) and modified clay (Cloisite 20A)] in the terpolymer of vinylidene fluoride, hexafluoropropylene and tetrafluoroethylene (fluoroelastomer). The phase images of the above nanocomposites elucidated that the width of clay particles was lower in the case of the unmodified clay filled system. Interestingly, the polymer was able to exfoliate both the unmodified and modified clays. This phenomenon was supported by transmission electron microscopy and X-ray diffraction studies. The results obtained from the section analysis and the histogram of the filler distribution further supported the above findings. The surface roughness was less in the case of the unmodified clay based nanocomposite, as determined from roughness, power spectral density and fractal analysis. The study also indicated an improved particle distribution in the case of the unmodified clay filled samples. The results were explained with the help of thermodynamics and soft-hard acid base theory.     

New insights into tricalcium silicate hydration in paste

The knowledge of the aqueous phase composition during the hydration of tricalcium silicate (C₃S) is a key issue for the understanding of cement hydration. A new in situ method of computing calcium ion concentration from the measurement of the electrical conductivity on paste was coupled to isothermal calorimetry and BET measurements to get new insights on the early hydration of C₃S. Ion concentrations of the aqueous phase are mainly dependent on the degree of hydration and the water to C₃S ratio. In the case of C₃S paste, the calcium and silicon concentrations determined at low degrees of hydration can be related to the equilibrium curve of C-S-H having C/S = 1.27 and named C_1.27SH_y. It is expected that C_1.27SH_y thermodynamically controls the aqueous phase composition at this early stage. Indeed, the formation of C_1.27SH_y is quasi-immediate when C₃S is in contact with water inducing a very rapid increase of the specific surface area that remains constant during the induction period. At higher degrees of hydration, the aqueous phase composition departs from the C_1.27SH_y equilibrium curve. C_1.27SH_y appears to be a metastable C-S-H that could be related to an intermediate phase previously reported. The quasi-immediate precipitation of C_1.27SH_y on C₃S surface explains why calcium and silicon concentrations remain low during early hydration even though C₃S is strongly undersaturated. This also agrees with the control of the end of the induction period by the nucleation and growth of more stable C-S-H.