Slag Properties in the Primary Production Process of Mn-Ferroalloys

The thermodynamic and kinetic properties of the carbothermic reduction of MnO in the five-component slag, MnO-SiO2-CaO-MgO-Al2O3, is critical in the production process of Mn-ferroalloys. While the reduction rate is mainly dependent on the presence of a solid MnO phase in the slag for Mn-Fe-alloys, the rate for the Mn-Si-Fe alloys has two distinct steps, a slow step followed by a fast step. The extent of the slow step has been shown to be dependent on the S content in the slag. The thermo-physical properties of viscosity, density, interfacial tension and electrical resistivity is reviewed, and these properties are mainly determined by the total basicity.

Understanding the reaction mechanism of the regioselective piperidinolysis of aryl 1-(2,4-dinitronaphthyl) ethers in DMSO: Kinetic and DFT studies

Reactions of aryl 1-(2,4-dinitronaphthyl) ethers with piperidine in dimethyl sulfoxide at 25oC resulted in substitution of the aryloxy group at the ipso carbon atom. The reaction was measured spectrophotochemically and the kinetic studies suggested that the titled reaction is accurately third order. The mechanism is began by fast nucleophilic attack of piperidine on C1 to form zwitterion intermediate (I) followed by deprotonation of zwitterion intermediate (I) to the Meisenheimer ion (II) in a slow step, that is, SB catalysis. The regular variation of activation parameters suggested that the reaction proceeded through a common mechanism. The Hammett equation using reaction constant σo values and Brønsted coefficient value showed that the reaction is poorly dependent on aryloxy substituent and the reaction was significantly associative and Meisenheimer intermediate-like. The mechanism of piperidinolysis has been theoretically investigated using density functional theory method using B3LYP/6-311G(d,p) computational level. The combination between experimental and computational studies predicts what mechanism is followed either through uncatalyzed or catalyzed reaction pathways, that is, SB and SB-GA. The global parameters of the reactants, the proposed activated complexes, and the local Fukui function analysis explained that C1 carbon atom is the most electrophilic center of ether. Also, kinetics and theoretical calculation of activation energies indicated that the mechanism of the piperidinolysis passed through a two-step mechanism and the proton transfer process was the rate determining step.

Brønsted Acid Catalysis in the Oxidation of Purine Based Alkaloids by Mn(VII) in Aqueous Acetonitrile and Sodium Fluoride Medium: A Kinetic Approach

Brønsted acid (HClO4, H2SO4) catalyzed Mn(VII) oxidation of purine alkaloids such as caffeine, theophylline and theobromine in aqueous acetonitrile and sodium fluoride medium revealed first order kinetics in both [(Mn(VII)] and [Alkaloid] at constant acidity and temperature. Sodium fluoride was added to the reaction mixture in order to avoid/suppress auto catalytic reaction due to the generation of Mn(III) and Mn(IV) species during the course of Mn(VII) oxidations in acidic solutions. An increase in the Brønsted acids (HClO4, H2SO4) concentration accelerated the rate of oxidation. Rate enhancements observed here in are analyzed by Zucker-Hammett, Bunnett and Bunnett-Olsen criteria of acidity functions. On the basis of observed Bunnett-Olsen criteria of acidity functions, the most plausible mechanism has been proposed with the involvement of water molecule in the slow step (as proton transferring agent).

Kinetics of cytochrome P450 3A4 inhibition by heterocyclic drugs defines a general sequential multi-step binding process

Cytochrome P450 (P450, CYP) 3A4 is the enzyme most involved in the metabolism of drugs and can also oxidize numerous steroids. This enzyme is also involved in one-half of pharmacokinetic drug-drug interactions, but details of the exact mechanisms of P450 3A4 inhibition are still unclear in many cases. Ketoconazole, clotrimazole, ritonavir, indinavir, and itraconazole are strong inhibitors; analysis of the kinetics of reversal of inhibition with the model substrate 7-benzoyl (OBz) quinoline showed lag phases in several cases, consistent with multiple structures of P450 3A4 inhibitor complexes. Lags in the onset of inhibition were observed when inhibitors were added to P450 3A4 in 7-OBz quinoline O-debenzylation reactions, and similar patterns were observed for inhibition of testosterone 6β-hydroxylation by ritonavir and indinavir. Upon mixing with inhibitors, P450 3A4 showed rapid binding as judged by a spectral shift with at least partial high-spin iron character, followed by a slower conversion to a low-spin iron-nitrogen complex. The changes were best described by two intermediate complexes, one being a partial high-spin form and the second another intermediate, with half-lives of seconds. The kinetics could be modeled in a system involving initial loose binding of inhibitor, followed by a slow step leading to a tighter complex on a multi-second time scale. Although some more complex possibilities cannot be dismissed, these results describe a system in which conformationally distinct forms of P450 3A4 bind inhibitors rapidly and two distinct P450-inhibitor complexes exist enroute to the final enzyme-inhibitor complex with full inhibitory activity.

Histidine adsorption onto modified montmorillonite under prebiotic chemistry conditions: a thermodynamic and kinetic study

The origin of life from inanimate matter is still an open question, and our knowledge is still very limited. In this sense, prebiotic chemistry seeks to study and understand how chemical reactions may have contributed to the origin of life. Minerals are of great relevance to prebiotic chemistry, as they may have preconcentrated precursors of biomolecules or biomolecules from diluted solutions, provided protection for biomolecules against UV radiation and hydrolysis, catalysing their reactions and played the role of a primitive genetic code. Montmorillonite, a prebiotic mineral, was shown to be able to adsorb adenine and later also histidine. In addition, histidine adsorption did not displace adenine from the montmorillonite. Kinetic experiments showed that using a whole period of time (7 days) it was not possible to adjust the data to any mathematical kinetic model. Thus, the data were separated into four different adsorption ranges: range 1 (0–60 min), range 2 (60–4320 min), range 3 (4320–7200 min) and range 4 (7200–10 080 min). Range 1 showed adsorption that was too fast, meaning no variations in the adsorption data, and the data of range 3 did not fit in any model used in this work. Thus, range 2 (60–4320 min) and range 4 (7200–10 080 min) were analysed. The adsorption kinetics of histidine adsorption indicated two reaction steps, a quick step (60–4320 min), following the pseudo-first-order model, followed by a slower step (7200–10 080 min) of the pseudo-second order. With these results, isotherms were constructed with times of 1 h and 7 days. The results of the quick step (1 h) showed a reaction that was not thermodynamically favoured. For this time range, Gibbs energy values obtained ranged between 5 and 10 kJ mol−1 at temperatures of 20, 35 and 50°C, and the adsorption occurred due to the balance shift of increase in histidine concentrations. The isotherms of the slow step (7 days) presented negative values, showing a more favourable reaction with Gibbs energy values ranging between −5 and −11 kJ mol−1. The mathematical modelling of the data indicates that seawater ions are crucial in the adsorption process. Thus, the study provided essential information for prebiotic chemistry, showing that time and the reaction medium should always be taken into account.

Estudo teórico da formação da isatina e de seus derivados dimetoxilados pelo método Sandmeyer

Isatin has been attracted the researchers attention due the structural versatility and can be used to synthesized other molecules with pharmacological activities. The Sandmeyer method is one of the most common methods for the synthesis of this molecule. Where the reaction with from aniline with chloral hydrate and hydroxyl amine occurs with good yield. When the same reaction is performed with dimethoxylated aniline show low yield or is not observed experimentally. These observations motivate this work and the justification for these facts are given in terms of thermodynamic parameters and by the intermediaries formed during the reactions. In this study, two steps with great relevance in the synthetic route were analyzed: the nucleophilic attack and the cyclization. For this, electronic structure calculations were carried out using the functional B3LYP and the base set 6-311+G(d). In all the three cases investigated were idenfied a transition state in nucleophilic attack. This result is not reported in the literature. The energy barriers found show that this step is determinant to kinetic reaction because can be considered the slow step (barrier energy around 38 kcal mol-1). Ciclization step was highly spontaneous in all the cases studied.

KIF3A accelerates KIF3C within the kinesin-2 heterodimer to generate symmetrical phosphate release rates for each processive step

Heterodimeric KIF3AC is a mammalian kinesin-2 that is highly expressed in the central nervous system and is associated with vesicles in neurons. KIF3AC is an intriguing member of the kinesin-2 family because the intrinsic kinetics of KIF3A and KIF3C when expressed as homodimers and analyzed in vitro are distinctively different from each other. For example, the single-molecule velocities of the engineered homodimers KIF3AA and KIF3CC are 293 nm/s and 7.5 nm/s, respectively, whereas KIF3AC has a velocity of 186 nm/s. These results led us to hypothesize that heterodimerization alters the intrinsic catalytic properties of the two heads, and an earlier computational analysis predicted that processive steps would alternate between a fast step for KIF3A followed by a slow step for KIF3C resulting in asymmetric stepping. To test this hypothesis directly, we measured the presteady-state kinetics of phosphate release for KIF3AC, KIF3AA, and KIF3CC followed by computational modeling of the KIF3AC phosphate release transients. The results reveal that KIF3A and KIF3C retain their intrinsic ATP binding and hydrolysis kinetics. Yet within KIF3AC, KIF3A activates the rate of phosphate release for KIF3C such that the coupled steps of phosphate release and dissociation from the microtubule become more similar for KIF3A and KIF3C. These coupled steps are the rate-limiting transition for the ATPase cycle suggesting that within KIF3AC, the stepping kinetics are similar for each head during the processive run. Future work will be directed to define how these properties enable KIF3AC to achieve its physiological functions.

A computational study of the SNAr reaction of 2-ethoxy-3,5-dinitropyridine and 2-methoxy-3,5-dinitropyridine with piperidine

A computational study of the chemical kinetics and thermodynamics study of the SNAr between 3,5-dinitroethoxypyridine 1a and 3,5-dinitromethoxypyridine 1b with piperidine 2 in the gas phase is reported using hybrid density functional theory method B3PW91 and 6–31G(d,p) basis set. The reaction was modeled via both the catalyzed and base-catalyzed pathways which proceeded with the initial attack of the nucleophile 2 on the substrates 1 to yield the Meisenheimer complex intermediate that is stabilized with hydrogen bonding. Calculations show that the reaction goes via the formation and decomposition of a Meisenheimer complex, which was observed to be stabilized by hydrogen bonding. Along the uncatalyzed pathway, the decomposition of the Meisenheimer complex was the slow step and requires about 28 kcal/mol. This barrier was reduced to about 14.8 kcal/mol with the intervention of the base catalyst, thus making the formation of the Meisenheimer complex rate determining. All reactions were calculated to be exothermic, about −6.5 kcal/mol and −0.6 kcal/mol, respectively, for the reaction of 1a and 1b with 2.

Mechanism and kinetics of copper complexes binding to the influenza A M2 channel

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases in contrast to the single phase found for amantadine block of WT M2. Here we evaluate the mechanism of block by copper adamantyl iminodiacitate (Cu(AMT-IDA)) and copper cyclooctyl iminodiacitate (Cu(CO-IDA)) complexes and address whether the complexes can covalently bind to one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper-complex binding within the channel and the slow step in the current block is the covalent bond formation between copper complex and histidine. Isothermal titration calorimetry (ITC) indicates that a single imidazole binds strongly to the copper complexes. Structural optimization using density functional theory (DFT) reveals that the complexes fit inside the channel and project the Cu(II) towards the His37 cluster allowing one imidazole to form a covalent bond with the Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant in spite of some crowding in the binding site by the glutamates.

Evidence Regarding Automatic Processing Computerized Tasks Designed For Health Interventions in Real-World Settings Among Adults: Systematic Scoping Review

Background Dual process theories propose that the brain uses 2 types of thinking to influence behavior: automatic processing and reflective processing. Automatic processing is fast, immediate, nonconscious, and unintentional, whereas reflective processing focuses on logical reasoning, and it is slow, step by step, and intentional. Most digital psychological health interventions tend to solely target the reflective system, although the automatic processing pathway can have strong influences on behavior. Laboratory-based research has highlighted that automatic processing tasks can create behavior change; however, there are substantial gaps in the field on the design, implementation, and delivery of automatic processing tasks in real-world settings. It is important to identify and summarize the existing literature in this area to inform the translation of laboratory-based research to real-world settings. Objective This scoping review aims to explore the effectiveness of automatic training tasks, types of training tasks commonly used, mode of delivery, and impacts of gamification on automatic processing tasks designed for digital psychological health interventions in real-world settings among adults. Methods The scoping review methodology proposed by Arskey and O’Malley and Colquhoun was applied. A scoping review was chosen because of the novelty of the digital automatic processing field and to encompass a broad review of the existing evidence base. Electronic databases and gray literature databases were searched with the search terms “automatic processing,” “computerised technologies,” “health intervention,” “real-world,” and “adults” and synonyms of these words. The search was up to date until September 2018. A manual search was also completed on the reference lists of the included studies. Results A total of 14 studies met all inclusion criteria. There was a wide variety of health conditions targeted, with the most prevalent being alcohol abuse followed by social anxiety. Attention bias modification tasks were the most prevalent type of automatic processing task, and the majority of tasks were most commonly delivered over the web via a personal computer. Of the 14 studies included in the review, 8 demonstrated significant changes to automatic processes and 4 demonstrated significant behavioral changes as a result of changed automatic processes. Conclusions This is the first review to synthesize the evidence on automatic processing tasks in real-world settings targeting adults. This review has highlighted promising, albeit limited, research demonstrating that automatic processing tasks may be used effectively in a real-world setting to influence behavior change.