Stereoselective Reactions of δ2-Isoxazoline Exo-azaenolates. A Model for Construction of the C-Ring of Sesbanimide A

A Stereoselective aldol reaction between bis(tert-butyldimethylsilyloxy) acetone and an isoxazoline-derived azaenolate is a key step in the construction of a C-ring model of sesbanimide A.     

Photomodulated Azoaldolase: A Model for Light Intervention in Biological Systems?

Azoaldolase is obtained from rabbit muscle aldolase by adding an azo chromophore to a cysteine side chain in each of the four enzyme subunits. The enzyme becomes photosensitive whereas both its catalytic activity and the michaelian kinetics are retained. Chromophore excitation causes E to Z isomerization of the azo bond, and mutually influences the protein-substrate equilibria. The various isomerization and substrate binding equilibria have been investigated under the hypothesis of a cyclic process described by four linked equilibrium constants. The mechanism of the light effect is a continuous adaptation of the specific parameters of the active protein, that is substrate recognition and rate of the catalyzed process. Absorbed light allows the rapid modification of the concentrations of various related molecules, depending on the used frequencies. At present such a mechanism has not been described in photobiology; so azoaldolase can be taken as a model for a possible new mechanism of light regulation of a biological system, based on changes in the molecular recognition by an active protein against its substrate.     

How do azoles inhibit cytochrome P450 enzymes? A density functional study

To examine how azole inhibitors interact with the heme active site of the cytochrome P450 enzymes, we have performed a series of density functional theory studies on azole binding. These are the first density functional studies on azole interactions with a heme center and give fundamental insight into how azoles inhibit the catalytic function of P450 enzymes. Since azoles come in many varieties, we tested three typical azole motifs representing a broad range of azole and azole-type inhibitors: methylimidazolate, methyltriazolate, and pyridine. These structural motifs represent typical azoles, such as econazole, fluconazole, and metyrapone. The calculations show that azole binding is a stepwise mechanism whereby first the water molecule from the resting state of P450 is released from the sixth binding site of the heme to create a pentacoordinated active site followed by coordination of the azole nitrogen to the heme iron. This process leads to the breaking of a hydrogen bond between the resting state water molecule and the approaching inhibitor molecule. Although, formally, the water molecule is released in the first step of the reaction mechanism and a pentacoordinated heme is created, this does not lead to an observed spin state crossing. Thus, we show that release of a water molecule from the resting state of P450 enzymes to create a pentacoordinated heme will lead to a doublet to quartet spin state crossing at an Fe-OH(2) distance of approximately 3.0 A, while the azole substitution process takes place at shorter distances. Azoles bind heme with significantly stronger binding energies than a water molecule, so that these inhibitors block the catalytic cycle of the enzyme and prevent oxygen binding and the catalysis of substrate oxidation. Perturbations within the active site (e.g., a polarized environment) have little effect on the relative energies of azole binding. Studies with an extra hydrogen-bonded ethanol molecule in the model, mimicking the active site of the CYP121 P450, show that the resting state and azole binding structures are close in energy, which may lead to chemical equilibrium between the two structures, as indeed observed with recent protein structural studies that have demonstrated two distinct azole binding mechanisms to P450 heme.     

Which surfactants reduce surface tension faster? A scaling argument for diffusion-controlled adsorption

Consider the example of surfactant adsorbing from an infinite solution to a freshly formed planar interface. There is an implicit length scale in this problem, the adsorption depth h, which is the depth depleted to supply the interface with the absorbed surfactant. From a mass balance, h can be shown to be the ratio of the equilibrium surface concentration gamma eq to the bulk concentration C infinity. The characteristic time scale for diffusion to the interface is tau D = h2/D, where D is the diffusivity of the surfactant in solution. The significance of this time scale is demonstrated by numerically integrating the equations governing diffusion-controlled adsorption to a planar interface. The surface tension equilibrates within 1-10 times tau D regardless of bulk concentration, even for surfactants with strong interactions. Dynamic surface tension data obtained by pendant bubble method are rescaled using tau D to scale time. For high enough bulk concentrations, the re-normalized surface tension evolutions nearly superpose, demonstrating that tau D is indeed the relevant time scale for this process. Surface tension evolutions for a variety of surfactants are compared. Those with the smallest values for tau D equilibrate fastest. Since diffusion coefficients vary only weakly for surfactants of similar size, the differences in the equilibration times for various surfactant solutions can be attributed to their differing adsorption depths. These depth are determined by the equilibrium adsorption isotherms, allowing tau D to be calculated a priori from equilibrium surface tension data, and surfactant solutions to be sorted in terms of which will reduce the surface tension more rapidly. Finally, trends predicted by tau D to gauge what surfactant properties are required for rapid surface tension reduction are discussed. These trends are shown to be in agreement with guiding principles that have been suggested from prior structure-property studies.     

Is Glyceryl Trinitrate,a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?

Oxidative stress induced by well-known toxins including ferric nitrilotriacetate (Fe-NTA), carbon tetrachloride (CCl₄) and thioacetamide (TAA) has been attributed to causing tissue injury in the liver and kidney. In this study, the effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester (l-NAME), a nitric oxide inhibitor on TAA-induced hepatic oxidative stress, GSH and GSH-dependent enzymes, serum transaminases and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [³H]-thymidine incorporation in rats were examined. The animals were divided into seven groups consisting of six healthy rats per group. The six rats were injected intraperitoneally with TAA to evaluate its toxic effect, improvement in its toxic effect if any, or worsening in its toxic effect if any, when given in combination with GTN or l-NAME. The single necrogenic dose of TAA administration caused a significant change in the levels of both hepatic and serum enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (GGT), glucose 6-phosphate dehydrogenase (G6PD), alanine aminotransferase (AST) and aspartate aminotransferase (ALT). In addition, treatment with TAA also augmented malondialdehyde (MDA), ornithine decarboxylase (ODC) activity and [³H]-thymidine incorporation in rats liver. Concomitantly, TAA treatment depleted the levels of GSH. However, most of these changes were alleviated by the treatment of animals with GTN dose-dependently. The protective effect of GTN against TAA was also confirmed histopathologically. The present data confirmed our earlier findings with other oxidants including Fe-NTA and CCl₄. The GTN showed no change whatsoever when administered alone, however when it was given along with TAA then it showed protection thereby contributing towards defending the role against oxidants-induced organ toxicity. Overall, GTN may contribute to protection against TAA-induced oxidative stress, toxicity, and proliferative response in the liver, according to our findings.     

How Is Oxygen Incorporated into Oxides? A Comprehensive Kinetic Study of a Simple Solid‐State Reaction with SrTiO3 as a Model Material

The kinetics of stoichiometry change of an oxide--a prototype of a simple solid-state reaction and a process of substantial technological relevance--is studied and analyzed in great detail. Oxygen incorporation into strontium titanate was chosen as a model process. The complete reaction can be phenomenologically and mechanistically understood beginning with the surface reaction and ending with the transport in the perovskite. Key elements are a detailed knowledge of the defect chemistry of the perovskite as well as the application of a variety of experimental and theoretical tools, many of them evolving from this study. The importance of the reaction and transport steps for (electro)chemical applications is emphasized.     

A Self‐Improved Water‐Oxidation Catalyst: Is One Site Really Enough?

The homogeneous catalysis of water oxidation by transition‐metal complexes has experienced spectacular development over the last five years. Practical energy‐conversion schemes, however, require robust catalysts with large turnover frequencies. Herein we introduce a new oxidatively rugged and powerful dinuclear water‐oxidation catalyst that is generated by self‐assembly from a mononuclear catalyst during the catalytic process. Our kinetic and DFT computational analysis shows that two interconnected catalytic cycles coexist while the mononuclear system is slowly and irreversibly converted into the more stable dinuclear system: an extremely robust water‐oxidation catalyst that does not decompose over extended periods of time.     

A Self‐Improved Water‐Oxidation Catalyst: Is One Site Really Enough?

The homogeneous catalysis of water oxidation by transition‐metal complexes has experienced spectacular development over the last five years. Practical energy‐conversion schemes, however, require robust catalysts with large turnover frequencies. Herein we introduce a new oxidatively rugged and powerful dinuclear water‐oxidation catalyst that is generated by self‐assembly from a mononuclear catalyst during the catalytic process. Our kinetic and DFT computational analysis shows that two interconnected catalytic cycles coexist while the mononuclear system is slowly and irreversibly converted into the more stable dinuclear system: an extremely robust water‐oxidation catalyst that does not decompose over extended periods of time.     

Long‐Chain Branching with Metallocene Catalysts: Is a Purely Kinetic Mechanism for Terminal Branching Sufficient?

Rate constants for long‐chain branch formation during ethylene polymerization with metallocene catalysts were estimated and compared to polymerization rate constants for long α‐olefins. Unexpectedly, these branching constants were found to be comparable to the reactivity ratios of much shorter α‐olefins. Micromixing effects or a parallel mechanism for long‐chain branch generation are proposed as possible explanations for this finding.

Comparison between the α‐olefin and branching incorporation rate constants, normalized by the propagation rate constant (the values estimated from ref. 1 are subject to a significant uncertainty because the reaction conditions are not provided. A 10 wt.‐% polymer fraction in the reactor was assumed to estimate these values).     

Is the 1 J PSe Coupling Constant a Reliable Probe for the Basicity of Phosphines? A 31P NMR Study

Abstract

The influence of different heteroaryl and functionalized aryl substituents on the electron-donating ability and basicity of the phosphorus atoms in heteroaryl phosphines and diphosphines has been determined by the use of the direct ¹J_PSe coupling constants of the corresponding selenides. The generality of the use of ³¹P–⁷⁷Se spin–spin coupling constants as probe for the basicity of phosphines is discussed as well as the scope and limits of this concept.

GRAPHICAL ABSTRACT      

Pretreatment,Anaerobic Codigestion,or Both? Which Is More Suitable for the Enhancement of Methane Production from Agricultural Waste?

Pretreatment and codigestion are proven to be effective strategies for the enhancement of the anaerobic digestion of lignocellulosic residues. The purpose of this study is to evaluate the effects of pretreatment and codigestion on methane production and the hydrolysis rate in the anaerobic digestion of agricultural wastes (AWs). Thermal and different thermochemical pretreatments were applied on AWs. Sewage sludge (SS) was selected as a cosubstrate. Biochemical methane potential tests were performed by mixing SS with raw and pretreated AWs at different mixing ratios. Hydrolysis rates were estimated by the best fit obtained with the first-order kinetic model. As a result of the experimental and kinetic studies, the best strategy was determined to be thermochemical pretreatment with sodium hydroxide (NaOH). This strategy resulted in a maximum enhancement in the anaerobic digestion of AWs, a 56% increase in methane production, an 81.90% increase in the hydrolysis rate and a 79.63% decrease in the technical digestion time compared to raw AWs. On the other hand, anaerobic codigestion (AcoD) with SS was determined to be ineffective when it came to the enhancement of methane production and the hydrolysis rate. The most suitable mixing ratio was determined to be 80:20 (Aws/SS) for the AcoD of the studied AWs with SS in order to obtain the highest possible methane production without any antagonistic effect.     

Gold for C?C Coupling Reactions: A Swiss‐Army‐Knife Catalyst?

For organic chemists, the construction of C C bonds is the most essential aspect of the assembly of molecules. Transition‐metal‐catalyzed coupling reactions have evolved as one of the key tools for this task. Lately, gold has also emerged as a catalyst for this kind of transformation. Gold, with its special properties as a mild carbophilic π Lewis acid, its ability to insert into C H bonds, and, as discovered recently, its ability to undergo redox transformations, offers the opportunity to apply all this potent proficiency for the construction of compounds in an efficient and economical way. This Minireview critically presents the C C coupling reactions enabled by gold catalysts to encourage further research activities in this promising area of oxidation/reduction gold catalysts.