Oxidation Step Research Articles

Rh-Catalyzed [4 + 1] Reaction of Cyclopropyl-Capped Dienes (but not Common Dienes) and Carbon Monoxide: Reaction Development and Mechanistic Study.

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) is the most straightforward and easily envisioned cyclization for the synthesis of five-membered carbocycles, which are ubiquitously found in natural products and functional molecules. Unfortunately, no test of this reaction was reported, and consequently, chemists do not know whether such kind of reaction works or not. Herein, we report that the [4 + 1] reaction of common dienes and CO cannot work, at least under the catalysis of [Rh(cod)Cl]2. However, using cyclopropyl-capped dienes (also named allylidenecyclopropanes) as substrates, the corresponding [4 + 1] reaction with CO proceeds smoothly in the presence of [Rh(cod)Cl]2. This [4 + 1] reaction, with a broad scope, provides efficient access to five-membered carbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadducts can be further transformed into other molecules by using the unique chemistry of cyclopropyl groups present in these molecules. The mechanism of this [4 + 1] reaction has been investigated by quantum chemical calculations, uncovering that cyclopropyl-capped dienes are strained dienes and the oxidative cyclization step in the [4 + 1] catalytic cycle can release this (angular) strain both kinetically and thermodynamically. The strain release in this step then propagates to all followed CO coordination/CO insertion/reductive elimination steps in the [4 + 1] catalytic cycle, helping the realization of this cycloaddition reaction. In contrast, common dienes (including cyclobutyl-capped dienes) do not have such advantages and their [4 + 1] reaction suffers from energy penalty in all steps involved in the [4 + 1] catalytic cycle. The reactivity of ene-allenes for the [4 + 1] reaction with CO is also discussed.

Remarkably Selective Binding, Behavior Modification, and Switchable Release of (Bipyridine)3Ru(II) vis-à-vis (Phenanthroline)3Ru(II) by Trimeric Cyclophanes in Water.

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, the more valuable the dream becomes. We now present multianionic trimeric cyclophane receptors with a remarkable ability to bind the iconic (bipyridine)3Ru(II) (with its huge range of applications) while rejecting the nearly equally iconic (phenanthroline)3Ru(II). These receptors not only selectively capture (bipyridine)3Ru(II) but also can be redox-switched to release the guest. 1D- and 2D(ROESY)-NMR spectroscopy, luminescence spectroscopy, and molecular modeling enabled this discovery. This outcome allows the control of these applications, e.g., as a photocatalyst or as a luminescent sensor, by selectively hiding or exposing (bipyridine)3Ru(II). Overall, a 3D nanometric object is selected, picked-up, and dropped-off by a discrete molecular host. The multianionic receptors protect excited states of these metal complexes from phenolate quenchers so that the initial step in photocatalytic phenolate oxidation is retarded by nearly 2 orders of magnitude. This work opens the way for (bipyridine)3Ru(II) to be manipulated in the presence of other functional nano-objects so that many of its applications can be commanded and controlled. We have a cyclophane-based toolkit that can emulate some aspects of proteins that selectively participate in cell signaling and metabolic pathways by changing shape upon environmental commands being received at a location remote from the active site.

How chloride functions to enable proton conduction in photosynthetic water oxidation: Time-resolved kinetics of intermediates (S-states) in vivo and bromide substitution

Chloride (Cl−) is essential for O2 evolution during photosynthetic water oxidation. Two chlorides near the water-oxidizing complex (WOC) in Photosystem II (PSII) structures from Thermosynechococcus elongatus (and T. vulcanus) have been postulated to transfer protons generated from water oxidation. We monitored four criteria: primary charge separation flash yield (P* → P+QA−), rates of water oxidation steps (S-states), rate of proton evolution, and flash O2 yield oscillations by measuring chlorophyll variable fluorescence (P* quenching), pH-sensitive dye changes, and oximetry. Br-substitution slows and destabilizes cellular growth, resulting from lower light-saturated O2 evolution rate (−20 %) and proton release (−36 % ΔpH gradient). The latter implies less ATP production. In Br- cultures, protonogenic S-state transitions (S2 → S3 → S0’) slow with increasing light intensity and during O2/water exchange (S0’ → S0 → S1), while the non-protonogenic S1 → S2 transition is kinetically unaffected. As flash rate increases in Cl− cultures, both rate and extent of acidification of the lumen increase, while charge recombination is suppressed relative to Br−. The Cl− advantage in rapid proton escape from the WOC to lumen is attributed to correlated ion-pair movement of H3O+Cl− in dry water channels vs. separated Br− and H+ ion movement through different regions (>200-fold difference in Bronsted acidities). By contrast, at low flash rates a previously unreported reversal occurs that favors Br− cultures for both proton evolution and less PSII charge recombination. In Br− cultures, slower proton transfer rate is attributed to stronger ion-pairing of Br− with AA residues lining the water channels. Both anions charge-neutralize protons and shepherd them to the lumen using dry aqueous channels.

Inactivation of vitamin D2 metabolites by human CYP24A1

Vitamin D is found in two forms in humans, D3 produced in the skin and D2 solely from the diet. Both 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) are oxidised and inactivated by CYP24A1, a tightly regulated mitochondrial enzyme that controls serum levels of these secosteroids. The pathways of oxidation of 25(OH)D2 and 1,25(OH)2D2, particularly 25(OH)D2, by human CYP24A1 are not well characterized. The aim of this study was to further elucidate these pathways, and to compare the kinetics of metabolism of 25(OH)D2 and 1,25(OH)2D2 with their vitamin D3 counterparts. We used expressed and partially purified human CYP24A1 with substrates dissolved in the membrane of phospholipid vesicles, to mimic the inner mitochondrial membrane. We found that the major pathways for side chain oxidation of 25(OH)D2 and 1,25(OH)2D2 were identical and that predominant intermediates of 25(OH)D2 metabolism could be converted to the corresponding intermediates in the pathway of 1,25(OH)2D2 oxidation by 1α-hydroxylation by CYP27B1. The initial steps in the CYP24A1-mediated oxidation involved hydroxylation at the C24R position, and another unknown position where the alcohol was oxidised to an aldehyde. The 24R-hydroxylation was followed by hydroxylation at C26 or C28, or cleavage between C24 and C25 to produce the 24-oxo-25,26,27-trinor derivative. All of these products were further oxidised, with 24-oxo-25,26,27-trinor-1(OH)D2 giving a product tentatively identified as 24-oxo-25,26,27-trinor-1,28(OH)2D2. The catalytic efficiency (kcat/Km) of CYP24A1 for initial 25(OH)D2 hydroxylation was similar to that for 25(OH)D3, indicating that they have similar rates of inactivation at low substrate concentrations, supporting that vitamins D2 and D3 are equally effective in maintaining serum 25(OH)D concentrations. In contrast, the kcat/Km value for 1,25(OH)2D3 was almost double that for 1,25(OH)2D2 indicating a lower rate of inactivation of 1,25(OH)2D2 at a low substrate concentration, suggesting that it has increased metabolic stability in vivo.

Facile Chemical Synthesis of Co-Ru-Based Heterometallic Supramolecular Polymer for Electrochemical Oxidation of Bisphenol A: Kinetics Study at the Electrode/Electrolyte Interface.

Regardless of the adverse effects of Bisphenol A (BPA), its use in industry and in day-to-day life is increasing at a higher rate every year. In the present study, a simple and reliable chemical approach was used to develop an efficient BPA sensor based on a Co-Ru-based heterometallic supramolecular polymer (polyCoRu). Surface morphology and elemental analysis were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Furthermore, functional group analysis was accomplished by Fourier transform infrared spectroscopy (FT-IR). UV-vis spectroscopy was used to confirm the complexation in the ratio of 0.5:0.5:1 (metal 1/metal 2/ligand). Electrochemical characterization of the synthesized polyCoRu was conducted using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analyses. The study identified two distinct linear dynamic ranges for the detection of BPA, 0.197-2.94 and 3.5-17.72 μM. The regression equation was utilized to determine the sensitivity and limit of detection (LOD), resulting in values of 0.6 μA cm-2 μM-1 and 0.02 μM (S/N = 3), respectively. The kinetics of BPA oxidation at the polyCoRu/GCE were investigated to evaluate the heterogeneous rate constant (k), charge transfer coefficient (α), and the number of electrons transferred during the oxidation and rate-determining step. A probable electrochemical reaction mechanism has been presented for further comprehending the phenomena occurring at the electrode surface. The practical applicability of the fabricated electrode was analyzed using tap water, resulting in a high percentage of recovery ranging from 96 to 105%. Furthermore, the reproducibility and stability data demonstrated the excellent performance of polyCoRu/GCE.

A cold start-up method with combining chemical-looping combustion and catalytic combustion for a methanol reformer

The cold start-up time is crucial for an on-line methanol reformer. The light-off temperatures of methanol, H2 and CO catalytic combustion, the light-off temperatures of methanol decomposition and methanol steam reforming, and the light-off temperatures reducing oxidative copper-based catalysts/oxygen carriers (CCOCs) with methanol, H2 and CO were measured. According to these results, a novel cold start-up method with combining chemical-looping combustion and catalytic combustion (CLC&CC) over CCOCs was proposed in this paper. Firstly, the air is introduced into the reformer and the reformer is heated from the ambient temperature to the light-off temperatures of methanol catalytic combustion with the oxidation reaction heat of the reductive CCOCs, here a part of reductive CCOCs is transformed to oxidative CCOCs. Then, air and methanol are introduced into the reformer and the reformer is further heated to the required temperature with the heat of methanol catalytic combustion and the reduction heat of oxidative CCOCs. By decreasing the end temperature of the air oxidation step as low as its light-off temperature, the oxidation amount of reductive CCOCs, that is, the metallic Cu is greatly decreased, thus, the influence of a cold start-up on CCOCs is limited. Through 200 times cold start-up based on this method, the methanol steam reforming conversion was kept near 100%, while the cold start-up time decreased from 65 s to 62 s. This was in accordance with the characterization results that the dispersion of active substance of metallic Cu in CCOCs was significantly improved through the cold start-up.

Acidosis attenuates CPT-I-supported bioenergetics as a potential mechanism limiting lipid oxidation

Fuel interactions in contracting muscle represent a complex interplay between enzymes regulating carbohydrate and fatty acid catabolism, converging in the mitochondrial matrix. While increasing exercise intensity promotes carbohydrate use at the expense of fatty acid oxidation, the mechanisms underlying this effect remain poorly elucidated. As a potential explanation, we investigated whether exercise-induced reductions in intramuscular pH (acidosis) attenuate carnitine palmitoyltransferase-I (CPT-I)-supported bioenergetics, the rate-limiting step for fatty acid oxidation within mitochondria. Specifically, we assessed the effect of a physiologically relevant reduction in pH (pH 7.2 versus 6.8) on single and mixed substrate respiratory responses in murine skeletal muscle isolated mitochondria and permeabilized fibers. While pH did not influence oxidative phosphorylation stoichiometry (ADP/O ratios), coupling efficiency, oxygen affinity, or ADP respiratory responses, acidosis impaired lipid bioenergetics by attenuating respiration with L-carnitine and palmitoyl-CoA, while enhancing the inhibitory effect of malonyl-CoA on CPT-I. These acidotic effects were largely retained following a single bout of intense exercise. At rest, pyruvate and succinate-supported respiration were also impaired by acidosis. However, providing more pyruvate and ADP at pH 6.8 to model increases in glycolytic flux and ATP turnover with intense exercise overcame the acidotic attenuation of carbohydrate-linked oxidative phosphorylation. Importantly, this situation is fundamentally different from lipids where CPT-I substrate sensitivity and availability is impaired at higher power outputs suggesting lipid metabolism may be more susceptible to the effects of acidosis, possibly contributing to fuel shifts with increasing exercise intensity.

Thermally Methanol Oxidation via the Mn1@Co3O4(111) Facet: Non-CO Reaction Pathway.

Co3O4, as the support of single-atom catalysts, is effective in electron-structure modulation to get distinct methanol adsorption behaviors and adjustable reaction pathways for the methanol oxidation reaction. Herein, we considered the facets that constitute a Co vacancy of the Co3O4(111) facet and a foreign metal atom M (M = Fe, Ni, Cu, Ru, Rh, Pd, Ag, Os, Ir, Pt, Au, Mn) leading to single-atom catalysts. The Mn1@Co3O4(111) facet is the facet considered the most favorable among all of the possible terminations. Oxygen adsorption, decomposition, and its co-adsorption with methanol are the vital steps of methanol oxidation at the exposed Mn1@Co3O4(111) facet, giving rise to the stable configuration: two O* and one CH3OH* adsorbates. Then, the Mn1@Co3O4(111) facet activates the O-H and C-H bonds within CH3OH*, advances CH3O* → H2CO* → HCOO* → COO*, and releases the products H2, H2O, and CO2 consecutively.

High activity of CuO/#-Fe2O3 for low temperature CO oxidation: Effect of support crystal types in catalyst design

A series of Fe2O3 supported CuO catalysts were synthesized to investigate the effect of crystal types on CO oxidation performance of CuO/Fe2O3. The catalysts were characterized with BET surface area, XRD, Raman, O2-TPD, H2-TPR, XPS and in situ DRIFTS. The results showed that the crystal types had significant impact on the performance of CuO/Fe2O3, and the CuO/γ-Fe2O3 catalyst exhibited higher catalytic activity, which corresponding to 98.5% CO conversion at 180 °C. Besides, CuO/γ-Fe2O3 displayed better reducibility, which improved the redox cycle between Fe2+ and Fe3+ species. Furthermore, the pathway of CO oxidation on CuO/Fe2O3 followed L-H mechanism. Large amount of Fe2+ species and oxygen vacancies on CuO/γ-Fe2O3 increased the oxygen activation ability, which provided more reactive oxygen species to promote the rate-determining step in CO oxidation. Moreover, carbonate species on CuO/α-Fe2O3 were prone to accumulate, which resulted in the covering of active sites on catalyst surface and inhibited the adsorption and activation of CO and O2.

Understanding Formation and Roles of NiII Aryl Amido and NiIII Aryl Amido Intermediates in Ni-Catalyzed Electrochemical Aryl Amination Reactions.

Ni-catalyzed electrochemical aryl amination (e-amination) is an attractive, emerging approach to building C-N bonds. Here, we report in-depth experimental and computational studies that examined the mechanism of Ni-catalyzed e-amination reactions. Key NiII-amine dibromide and NiII aryl amido intermediates were chemically synthesized and characterized. The combination of experiments and DFT calculations suggest (1) there is coordination of an amine to the NiII catalyst before the cathodic reduction and oxidative addition steps, (2) a stable NiII aryl amido intermediate is produced from the cathodic half-reaction, a critical step in controlling the selectivity between cross-coupling and undesired homo-coupling reaction pathways, (3) the diazabicycloundecene additive shifts the aryl halide oxidative addition mechanism from a NiI-based pathway to a Ni0-based pathway, and (4) redox-active bromide in the supporting electrolyte functions as a redox mediator to promote the oxidation of the stable NiII aryl amido intermediate to a NiIII aryl amido intermediate. Subsequently, the NiIII aryl amido intermediate undergoes facile reductive elimination to provide a C-N cross-coupling product at room temperature. Overall, our results provide new fundamental understandings about this e-amination reaction and guidance for further development of other Ni-catalyzed electrosynthetic reactions such as C-C and C-O cross-couplings.

Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis.

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one of the most prevalent synthetic precursors to azetidines. Herein, we report an electrocatalytic method for intramolecular hydroamination of allylic sulfonamides to access azetidines for the first time. The merger of cobalt catalysis and electricity enables the regioselective generation of key carbocationic intermediates, which could directly undergo intramolecular C-N bond formation. The mechanistic investigations including electrochemical kinetic analysis suggest that either the catalyst regeneration by nucleophilic cyclization or the second electrochemical oxidation to access the carbocationic intermediate is involved in the rate-determining step (RDS) of our electrochemical protocol and highlight the ability of electrochemistry in providing ideal means to mediate catalyst oxidation.

Self-supported ultrathin NiCo layered double hydroxides nanosheets electrode for efficient electrosynthesis of formate

Electrochemical CO2 reduction into energy-carrying compounds, such as formate, is of great importance for carbon neutrality, which however suffers from high electrical energy input and liquid products crossover. Herein, we fabricated self-supported ultrathin NiCo layered double hydroxides (LDHs) electrodes as anode for methanol electrooxidation to achieve a high formate production rate (5.89 mmol h−1 cm−2) coupled with CO2 electro-reduction at the cathode. A total formate faradic efficiency of both anode for methanol oxidation and cathode for CO2 reduction can reach up to 188% driven by a low cell potential of only 2.06 V at 100 mA cm−2 in membrane-electrode assembly (MEA). Physical characterizations demonstrated that Ni3+ species, formed on the electrochemical oxidation of Ni-containing hydroxide, acted as catalytically active species for the oxidation of methanol to formate. Furthermore, DFT calculations revealed that ultrathin LDHs were beneficial for the formation of Ni3+ in hydroxides and introducing oxygen vacancy in NiCo-LDH could decrease the energy barrier of the rate-determining step for methanol oxidation. This work presents a promising approach for fabricating advanced electrodes towards electrocatalytic reactions.

Studying the mechanism and impact of H2O-rich atmosphere on N oxidation during ammonia combustion and ammonia-coal co-combustion

Carbon-free fuel ammonia and coal co-combustion, an effective way to reduce thermal power CO2 emissions, has attracted more and more attention in recent years. Due to the hydrogen-rich property of ammonia, more H2O is generated during combustion, and the high H2O atmosphere significantly affects the NOx formation. Therefore, it is necessary to explore the oxidation path of N in the combustion of ammonia and its coupling coal in the H2O atmosphere. In this study, quantum chemistry theory and transition state theory are used to investigate the influence mechanism of H2O atmosphere on the oxidation of ammonia and fuel-N in the ammonia-coal co-combustion. The results show that the presence of OH in the H2O atmosphere promotes the formation of NH2 and NH, which is conducive to their oxidation to HNO and NO. The condition without OH is conducive to the oxidation of ammonia to HNO, and the presence of OH promotes the further oxidation of HNO to NO in the co-combustion of ammonia and coal. The H2O atmosphere reduces the energy barrier value of rate-determing step for ammonia and coal char oxidation during co-combustion, and increases the oxidation rate of ammonia-N and char-N. This work reveals the molecular mechanism by which H2O atmosphere promotes the combination of OH and O2 to generate HO2, and discovers the temperature conditions for HO2 formation. This study provides theoretical support for the development of N oxidation mechanism in the ammonia-coal co-combustion.

Increasing CO2 gasification rates of longan-seed char by a technique of char pre-oxidation

A simple and effective technique was presented to increase the longan-seed char gasification rate during CO2 activation by pre-oxidizing the char with air. The kinetics of char gasification was studied in a thermogravimetric analyzer (TGA) for the temperatures of 850–950 °C for char samples being oxidized in a tube furnace at the temperatures of 250, 280, and 300 °C. It was found that the gasification rate of the oxidized char was about twice higher than that of the non-oxidized char. The increase in the char reactivity for CO2 gasification is due to the increasing number of reaction sites caused by the disruption of functional group bonding created during the oxidation step. Additionally, the increase in the oxidation temperature gave rise to the increase in the char reactivity but the maximum temperature was limited by the ignition temperature of the longan-seed char. Four gasification kinetic models were tested against the experimental rate data and it was discovered that the modified volume reaction model (MVRM) provided the best description of the gasification conversion. The pre-exponential factor and the activation energy of the gasification reaction were determined from the Arrhenius equation. The estimated activation energy was found to be in the range of 156.87–218.98 kJ/mol and decreased with the increase of char oxidation temperature.

Biosynthesis and biotechnological production of the anti-obesity agent celastrol.

Obesity is a major health risk still lacking effective pharmacological treatment. A potent anti-obesity agent, celastrol, has been identified in the roots of Tripterygium wilfordii. However, an efficient synthetic method is required to better explore its biological utility. Here we elucidate the 11 missing steps for the celastrol biosynthetic route to enable its de novo biosynthesis in yeast. First, we reveal the cytochrome P450 enzymes that catalyse the four oxidation steps that produce the key intermediate celastrogenic acid. Subsequently, we show that non-enzymatic decarboxylation-triggered activation of celastrogenic acid leads to a cascade of tandem catechol oxidation-driven double-bond extension events that generate the characteristic quinone methide moiety of celastrol. Using this acquired knowledge, we have developed a method for producing celastrol starting from table sugar. This work highlights the effectiveness of combining plant biochemistry with metabolic engineering and chemistry for the scalable synthesis of complex specialized metabolites.

Promoter doping for tuning the redox behavior of CuCl2/γ-Al2O3-based catalysts in ethylene oxychlorination: Insights from kinetic studies

This study investigates the promoter effects of 14 metal chlorides (NaCl, KCl, RbCl, CsCl, MgCl2, CaCl2, SrCl2, CeCl3, PrCl3, NdCl3, ErCl3, FeCl3, YCl3, and SnCl3) on the CuCl2/γ-Al2O3-based catalysts used for ethylene oxychlorination. The study combines transient experiments of the two half-reactions in the redox cycle to understand the effects of different promoters on the reduction and oxidation rates of the catalysts. The results show that promoter doping can tune the redox behavior of the CuCl2/γ-Al2O3-based catalysts, affecting the reduction and oxidation steps, and the rate-determining step (RDS) changed between reduction and oxidation steps through the effects of different promoters. All the promoters have a positive effect on the reaction rate at steady-state, but the impact of promoter identity on steady-state CuCl2 concentration is variable and related to the electronegativity of the promoter metal. This work provides a better understanding of the reaction process and mechanism and highlights the potential of promoter doping for improving the efficiency and stability of CuCl2/γ-Al2O3-based catalysts in ethylene oxychlorination. The approach of both transient and steady-state kinetic modeling and simulation is a reliable and efficient method to study promoter effects on reduction–oxidation reactions.

Enantioselective C−P Bond Formation through C(sp3)−H Functionalization

AbstractAn enantioselective C−P bond formation has been developed through a C(sp3)−H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been achieved following a one‐pot strategy, starting from different benzylic and allylic alcohols and dibenzyl phosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched α‐hydroxy phosphonates with yields from 40% to >95% and enantioselectivities from 64% to >99%. Furthermore, the use of this methodology has been demonstrated to form a tetrasubstituted carbon stereocenter, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents an asymmetric strategy for constructing chiral C−P bonds, which are of interest to the pharmaceutical industry.

Development of a Scalable Electrophilic Amination Protocol for the Multi-kg Production of 5-Methyl-2-pyridinesulfonamide: A Regulatory Starting Material of Endothelin Receptor Antagonist Clazosentan

5-Methyl-2-pyridinesulfonamide is a regulatory starting material of endothelin receptor antagonist clazosentan. The original route to the key sulfonamide relied on the textbook conversion of the corresponding thiophenol to the intermediate sulfonyl chloride followed by its quenching with aqueous ammonia. However, this route suffered from a wide range of issues such as a low overall yield (29%), challenging aqueous workups and isolations, and the formation of a genotoxic benzyl chloride impurity. Therefore, we developed a conceptually novel production route for 5-methyl-2-pyridinesulfonamide. The new process relied on selectively oxidizing the thiophenol to the intermediate sulfinate salt followed by an electrophilic amination of the nucleophilic sulfinate sulfur-atom with hydroxylamine-O-sulfonic acid (HOSA). This oxidation/electrophilic amination sequence worked as a “one-pot” procedure by simply adding HOSA to the reaction mixture after complete oxidation of the thiophenol with 70% aq. t-BuOOH. The process was extensively optimized with regard to the oxidation step, increasing the stability of HOSA in the reaction mixture, and the final isolation of 5-methyl-2-pyridinesulfonamide. The new process was performed on a 22 kg scale, delivering the desired product as a white solid in 69% overall yield and excellent purity (>99.9% a/a).

Oxidative dehydrogenation of alcohols on gold: An experimental and computational study on the role of water and the alcohol chain length

The oxidative dehydrogenation of primary alcohols promoted by gold nanoparticles was investigated from an experimental and computational viewpoint to derive a plausible reaction mechanism and to understand the role of water and alcohol chain length in the elementary steps. The influence of water in reaction kinetics and product distribution was determined in a laboratory-scale microreactor adding water to the reaction mixture in different amounts. DFT calculations revealed that the presence of water on the catalyst surface is beneficial to assist the key step in alcohol oxidation i.e., oxygen activation by protonation. The calculations were performed for primary alcohols ranging from methanol to butanol to understand the role of the alkyl chain length on the catalytic activity and to clarify experimental observations. General conclusions were drawn on the influence of temperature on product distribution when employing a typical support material for gold nanoparticles, Al2O3. The combination of experiments and theory has been useful to improve the knowledge of alcohol oxidation promoted by gold.

Dual targeting of wild-type p53 and gut microbiota by Magnolol represses key metabolic process and kills CRC cells.

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.