Catalytic Mode Research Articles

Tetrahydrobiopterin and Nitric Oxide Synthase Recouplers.

Generation of nitric oxide (NO) by the nitric oxide synthase (NOS) enzymes plays multiple signalling roles in every organ system, with crucial roles in the cardiovascular system, mediated by endothelial nitric oxide synthase (eNOS, encoded by NOS3) and neuronal nitric oxide synthase (nNOS, encoded by NOS1) in regulation of blood pressure, flow, oxygen delivery and cardiac function. Loss of normal NO-mediated functions in cardiovascular disease state is associated with changes in nitroso-redox signalling that are not dependent solely upon altered NO generation, but increased generation of reactive oxygen species (ROS). The NOS enzymes can also generate ROS, in a catalytic mode whereby the generation of NO from L-arginine is 'uncoupled' from the reduction of molecular oxygen. NOS uncoupling is determined by several factors, including the availability and oxidation state of the required NOS cofactor, tetrahydrobiopterin (BH4). The duality of NOS functions as enzymes that generate both NO and ROS under different regulatory states has emerged as an important pathophysiologic mechanism, and is a potential therapeutic target, via agents that can maintain or restore NOS coupling, for example via effects on BH4 availability.

The Degron Architecture of Squalene Monooxygenase and How Specific Lipids Calibrate Levels of This Key Cholesterol Synthesis Enzyme.

Cholesterol synthesis is a fundamental process that contributes to cellular cholesterol homeostasis. Cells execute transcriptional and post-translational mechanisms to control the abundance of enzymes of the cholesterol synthesis pathway, consequently affecting cholesterol production. One such highly tuned enzyme is squalene monooxygenase (SM), which catalyzes a rate-limiting step in the pathway. A well-characterized mechanism is the cholesterol-mediated degradation of SM. Notably, lipids (cholesterol, plasmalogens, squalene, and unsaturated fatty acids) can act as cellular signals that either promote or reduce SM degradation. The N-terminal region of SM consists of the shortest known cholesterol-responsive degron, characterized by atypical membrane anchoring structures, namely a re-entrant loop and an amphipathic helix. SM also undergoes non-canonical ubiquitination on serine, a relatively uncommon attachment site for ubiquitination. The structure of the catalytic domain of SM has been solved, providing insights into the catalytic mechanisms and modes of inhibition by well-known SM inhibitors, some of which have been effective in lowering cholesterol levels in animal models. Certain human cancers have been linked to dysregulation of SM levels and activity, further emphasizing the relevance of SM in health and disease.

Selective C-C Bond Scission of Ketones via Visible-Light-Mediated Cerium Catalysis

Summary Here, we report a general catalytic manifold for the selective C–C bond scission of ketones via the exploitation of the ligand-to-metal charge transfer (LMCT) excitation mode. Through a cooperative utilization of Lewis acid catalysis and LMCT catalysis, the C–C bond of ketones could be selectively and effectively cleaved, enabling the installation of different functionalities at each carbon of the cleaved C–C bond through a sequential and orthogonal manner. This reaction manifold serves as a photocatalytic alternative to the Norrish type I reaction with the combination of visible light and inexpensive cerium salts. Under operationally simple conditions, a wide range of acyclic and cyclic ketones, from simple strained cyclobutanones to complex androsterone with less strained cyclopentanone moiety, could be successfully transformed into versatile chemical building blocks.

Synergistic visible light photoredox catalysis

AbstractWithin the last decade the combination of photoredox catalysis and other catalytic modes of activation has become a powerful tool for organic synthesis to enable transformations that are not possible using single catalyst systems and hence are complementary to traditional methodology. Especially reactions proceeding via synergistic catalysis where co-catalyst and photocatalyst simultaneously and separately activate different reaction partners greatly benefit from the special properties of molecules and transition metal complexes in their excited state being oxidizing and reducing in nature at the same time. Apart from allowing for the generation of radical (open-shell) reactive intermediates by SET under mild conditions from bench-stable, abundant precursors, the photocatalyst often acts to interweave the distinct catalytic cycles by interaction at multiple points of the reaction mechanism to provide overall redox-neutral processes by shuttling electrons within in this complex network of elementary reaction steps. Synergistic strategies moreover may allow to performing such reactions with enantioselectivity, while mostly the selectivity is achieved by the chiral co-catalyst. The merger of photocatalysis has been achieved with a broad range of alternative modes of catalysis including organocatalysis, Brønstedt and Lewis acid and base catalysis, enzyme catalysis as well as in the context of cross-coupling transition metal catalysis overcoming challenging steps in this methodology and therefore has contributed to considerably expand the repertoire of suitable coupling partners. While only selected examples will be discussed, this chapter will highlight various dual catalytic platforms focusing on the photocatalytically generated intermediates, but also illustrating the diverse roles of photocatalysts in the context of such synergistic multicatalysis reactions.

Hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (αs1‐, β‐ and k‐casein) after enzymatic hydrolysis with pepsin and enzymatic extract from Pleurotus eryngii

SummaryThe aim of this study was to estimate the hydrolytic degree and antioxidant activity of purified casein characterised by different haplotypes (αs1‐, β‐ and k‐casein) after in vitro digestion with two different enzymatic systems: pepsin from porcine gastric mucosa (EP) and a crude enzymatic extract from the edible mushroom Pleurotus eryngii. The used enzymes showed a different mode of casein catalysis with a consequent production of peptides of different antioxidant activity. The CN haplotype significantly influenced peptides production; in fact, the amino acid substitutions caused by genetic polymorphisms at the αs1‐, β‐ and k‐CN loci influenced the sites of enzymatic cleavage and therefore the produced peptides. The above is evidenced by the different antioxidant activity found in the hydrolysates depending on the used enzymatic system, the CN haplotype, and the CN haplotype × enzymatic treatment interaction. The findings of this study are a perspective for the production of specific foods that exert a biological effect in addition to the nutritional one.

Copper(I)-Catalyzed Asymmetric Reactions Involving Radicals.

Asymmetric functionalization of alkyl radicals represents a robust yet underdeveloped method for efficient construction and decoration of carbon skeletons in chiral organic molecules. In this field, we have been inspired by the excellent redox, alkyl radical trapping, and Lewis acidic properties of copper to develop several catalytic modes for asymmetric reactions involving alkyl radicals. At the beginning, we discovered tandem radical hydrotrifluoromethylation of unactivated alkenes and enantioselective alkoxylation of remote C(sp3)-H bonds by copper/chiral phosphate relay catalysis. This success has stimulated us to develop an asymmetric three-component 1,2-dicarbofunctionalization of 1,1-diarylalkenes using a similar strategy via radical intermediates. Meanwhile, we also discovered a copper/chiral secondary amine cooperative catalyst for asymmetric radical intramolecular cyclopropanation of alkenes using α-aldehyde methylene groups as C1 sources. The trapping of alkyl radical intermediates by CuII species during the reaction was essential for the chemoselectivity toward cyclopropanation. Encouraged by the efficient enantiocontrol with chiral phosphate and the effective trapping of alkyl radicals with CuII species, we then sought to develop copper/chiral phosphate as a single-electron-transfer catalyst for asymmetric reactions involving alkyl radicals. Subsequently, we successfully achieved a series of highly enantioselective 1,2-aminofluoroalkylation, -aminoarylation, -diamination, -aminosilylation, and -oxytrifluoromethylation of unactivated alkenes. The key for high enantioinduction was believed to be the effective trapping of alkyl radicals by CuII/chiral phosphate complexes. Besides, an achiral pyridine ligand was found to be indispensable for achieving high enantioselectivity, presumably via stabilization of CuIII species in the 1,2-alkoxytrifluoromethylation reaction. This discovery reminded us of tuning the redox properties and chemoreactivity of copper centers with an ancillary ligand. As a result, we subsequently identified cinchona alkaloid-derived sulfonamides as novel neutral-anionic hybrid ligands for simultaneous chemo- and enantiocontrol. We thus accomplished highly enantioselective 1,2-iminoxytrifluoromethylation of unactivated alkenes under the catalysis of copper/cinchona alkaloid-derived sulfonamide ligand, affording trifluoromethylated isoxazolines in high enantiomeric excess. Our copper-catalyzed asymmetric reactions with alkyl radicals provide expedient access to a diverse range of valuable chiral molecules with broad application potential in areas of organic synthesis, medicine, agrochemical, and material sciences.

Cationic Organic Catalysts or Ligands in Concert with Metal Catalysts.

Cooperative dual catalysis and bifunctional catalysis have emerged as reliable strategies for the development of hitherto difficult asymmetric transformations because they could deliver new reactivity and selectivity, and allow for the employment of substrates not amenable to reaction systems relying on a single, monofunctional catalysts. Furthermore, these modes of catalysis often improve yields and stereoselectivities via the precise recognition and simultaneous activation of nucleophiles and electrophiles. Efforts towards utilizing chiral cationic organic catalysts for asymmetric cooperative catalysis with metal complexes have provided a unique platform to address the challenging issues associated with reaction development. Chiral onium ions, such as tetraalkylammonium, guanidinium, and azolium ions, are employed mainly to control the reactivity and stereochemistry of anionic intermediates through electrostatic and hydrogen-bonding interactions. Metal complexes complement the synergy of the catalysis by activating the substrates via the formation of electrophilic π-allyl complexes, Lewis acid-base adducts, nucleophilic ate complexes, etc. The electrostatic interactions between cations and anions also offer a means to construct complex molecular assemblies, and, thus, onium ions are useful not only for controlling pairing with anionic species, but also for the design of supramolecular catalysts. The combination of onium ions and metal complexes leads to the introduction of novel concepts and powerful strategies for the development of catalysts and chemical transformations.

Ketones and aldehydes as alkyl radical equivalents for C─H functionalization of heteroarenes.

The polar nature of the C═O bond commonly allows it to undergo direct attack by nucleophiles at the electrophilic carbon atom in which ketones and aldehydes act as alkyl carbocation equivalents. In contrast, transformations in which ketones and aldehydes act as alkyl radical equivalents (generated in carbonyl carbon) are unknown. Here, we describe a new catalytic activation mode that combines proton-coupled electron transfer (PCET) with spin-center shift (SCS) and enables C─H alkylation of heteroarenes using ketones and aldehydes as alkyl radical equivalents. This transformation proceeded via reductive PCET activation of the ketones and aldehydes to form α-oxy radicals, addition of the radicals to the N-heteroarenes to form C─C bonds, and SCS to cleave the C─O bonds of the resulting alcohols. This mild protocol represents a general use of abundant, commercially available, ketones and aldehydes as latent alkyl radical equivalents.

A New Strategy for Improving the Efficiency of Low-temperature Selective Catalytic Reduction of NOx with CH4via the Combination of Non-thermal Plasma and Ag2O/TiO2 Photocatalyst

In the present work, a remarkable combination of non-thermal plasma and photocatalyst was developed to widen the operating temperature window of selective catalytic reduction(SCR) of NOx with CH4, especially to im-prove the low-temperature removal efficiency of NOx. It was shown that the operating temperature window was significantly widened. Among all the catalysts prepared, 1%Ag2O/TiO2 showed the highest catalytic activity for NOx removal due to the utilization of near ultraviolet light. The conversion of NOx to N2 over the in-plasma 1%Ag2O/TiO2 photocatalyst at 60 and 300 °C could achieve 31.8% and 53.0%, respectively. The combination mode of plasma and catalyst affected NOx removal efficiency greatly, the in-plasma catalysis outperformed the post-plasma catalytic mode remarkably, signifying the contribution of photocatalytic processes on the catalysts. Meanwhile, the characterizations of the catalyst demonstrated that the morphology and structure of the Ag2O/TiO2 catalyst were unchanged throughout the non-thermal plasma and photocatalytic processes, implying the superior stability of the catalyst.

Microwave-assisted catalytic pyrolysis of torrefied corn cob for phenol-rich bio-oil production over Fe modified bio-char catalyst

Microwave-assisted catalytic pyrolysis of torrefied corn cob into phenol-rich bio-oil on Fe modified bio-char catalyst was investigated in this study. The well-developed surface pore was confirmed by scanning electronic microscope (SEM) images and nitrogen adsorption/desorption isotherms, indicating that the porous structure of bio-char depended on the Fe modification to a large extent. Temperature-programmed desorption of NH3 (NH3-TPD) analysis showed that the Fe modified bio-char catalyst mainly presented strong acid sites. The use of bio-char catalyst can decrease the bio-oil yield and increase the gas yield but the biochar did not experience any significant change because of the ex-situ catalysis mode. Catalytic pyrolysis of torrefied corn cob using Fe modified bio-char catalyst was able to produce the higher yields and selectivities of phenol and cresol, where the catalytic performance of the bio-char catalyst was superior to commercial activated carbon. In addition, the catalyst deactivation and regenation tests were also conducted to evaluate the service life of the catalyst.

Recent Advances in Enantioselective Photochemical Reactions of Stabilized Diazo Compounds.

Diazo compounds have proven to be a useful class of carbenes or metal carbenoids sources under thermal, photochemical, or metal-catalyzed conditions, which can subsequently undergo a wide range of synthetically important transformations. Recently, asymmetric photocatalysis has provoked increasing research interests, and great advances have been made in this discipline towards the synthesis of optically enriched compounds. In this context, the past two decades have been the most productive period in the developments of enantioselective photochemical reactions of diazo compounds due to a better understanding of the reactivities of diazo compounds and the emergence of new catalytic modes, as well as easier access to and treatment of stabilized diazo compounds. This review highlights these impressive achievements according to the reaction type, and the general mechanisms and stereochemical inductions are briefly discussed as well.

Highly effective microwave catalytic direct decomposition of H2S over carbon encapsulated Mo2C–Co2C/SiC composite

The direct decomposition of H2S into COx-free H2 and S is an attractive approach in respect of both environmental and energy advantages. However, to achieve the highly effective direct H2S decomposition reaction is a critical scientific challenge, owning to the serious thermal equilibrium limitation in this reaction. Herein, we develop carbon encapsulated Mo2C–Co2C/SiC composite (Mo2C–Co2C/SiC@C) via in-situ microwave carbonization, as a novel microwave catalyst for highly effective direct decomposition of H2S into COx-free H2 and S by microwave catalysis. Significantly, the H2S conversion is impressively up to 90.3% at 750 °C over Mo2C–Co2C/SiC@C microwave catalyst in the microwave catalytic reaction mode, which greatly surpasses the corresponding H2S equilibrium conversion in the conventional reaction mode. Importantly, Mo2C–Co2C/SiC@C exhibits outstanding stability under microwave irradiation. It is found that microwave catalysis can break the chemical equilibrium limitation of the H2S decomposition reaction, which displays a significant microwave selective catalytic effect. This work provides a novel route for high value utilization of toxic and abundant H2S resources, and thus opens a new approach for the design of high active and stable microwave catalysts in microwave catalytic reactions.

Frontiers in Halogen and Chalcogen-Bond Donor Organocatalysis.

Non‐covalent molecular interactions on the basis of halogen and chalcogen bonding represent a promising, powerful catalytic activation mode. However, these “unusual” non‐covalent interactions are typically employed in the solid state and scarcely exploited in catalysis. In recent years, an increased interest in halogen and chalcogen bonding has been awaken, as they provide profound characteristics that make them an appealing alternative to the well‐explored hydrogen bonding. Being particularly relevant in the binding of “soft” substrates, the similar strength to hydrogen bonding interactions and its higher directionality allows for solution‐phase applications with halogen and chalcogen bonding as the key interaction. In this mini‐review, the special features, state‐of‐the‐art and key examples of these so‐called σ‐hole interactions in the field of organocatalysis are presented.

Kinetic study of thermal and catalytic hydrocracking of asphaltene

Abstract In this study, a five-lump model was proposed for kinetic modeling of asphaltene placed in a batch reactor with a commercial slurry-phase catalyst (Mo-octoate). Asphaltene was separated from vacuum residue using normal pentane. The kinetic experiments were carried out at 380∼430℃ for 1∼20 h together with a 1000 ppm concentration of Molybdenum in thermal and catalytic hydrocracking reaction modes. The results showed that the coke induction period and maximum maltene yield are changed with reaction temperature and time at thermal and catalytic hydrocracking. In addition, a linear relationship between coke and liquid (maltene + asphaltene remains) yields was shown so that the critical gas amount could be found as a criterion for determining the end of the coke induction period. Significantly, the kinetic model fit the experimental data well and, moreover, was found to be able to predict the moment when coke begins to form as well as maximum maltene yields.

Recent Advances in First-Row Transition Metal/Chiral Phosphoric Acid Combined Catalysis.

Since the pioneering independent reports of Akiyama and Terada, the use of chiral phosphoric acids (CPAs) and derivatives as a versatile tool for asymmetric synthesis with good reactivity, regioselectivity, diastereoselectivity and enantioselectivity has emerged, forming an important part of the implementation of asymmetric counteranion-directed catalysis reported to date. In these achievements, the combination of metals with CPAs has enabled various catalytic modes beyond the scope of typical acid catalysis, such as relay catalysis, ion-pairing catalysis, and binary acid catalysis. The first-row transition metals (Sc-Zn) are considered to be sustainable transition metals and have received a great deal of attention. These naturally abundant metals display excellent Lewis acidity and function as powerful redox catalysts in synthesis involving both one and two-electron transfers. Hence, in this chapter, we summarize recent advances in the development of asymmetric reactions using a combination of first-row transition metals and CPAs. Furthermore, we provide a detailed discussion of the mechanisms involved in order to understand the interaction of the metal/phosphate and the origins of the asymmetric control of the transformations.

Fast and selective organocatalytic ring-opening polymerization by fluorinated alcohol without a cocatalyst

Organocatalysis is an important branch of catalysis for various organic transformations and materials preparation. Polymerizations promoted by organic catalysts can produce polymeric materials without any metallic residues, providing charming materials for high-value and sensitive domains such as biomedical applications, microelectronic devices and food packaging. Herein, we describe a fluorinated alcohol based catalytic system for polypeptide synthesis via catalytic ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydride (NCA), fulfilling cocatalyst free, metal free, high rate and high selectivity. During polymerization, the fluorinated alcohol catalyst forms multiple dynamic hydrogen bonds with the initiator, monomer and propagating polymer chain. These cooperative hydrogen bonding interactions activate the NCA monomers and simultaneously protect the overactive initiator/propagating polymer chain-ends, which offers the whole polymerization with high activity and selectivity. Mechanistic studies indicate a monocomponent-multifunctional catalytic mode of fluorinated alcohol. This finding provides a metal free and fast approach to access well-defined polypeptides.

Catalytic Knockdown of miR-21 by Artificial Ribonuclease: Biological Performance in Tumor Model.

Control of the expression of oncogenic small non-coding RNAs, notably microRNAs (miRNAs), is an attractive therapeutic approach. We report a design platform for catalytic knockdown of miRNA targets with artificial, sequence-specific ribonucleases. miRNases comprise a peptide [(LeuArg)2Gly]2 capable of RNA cleavage conjugated to the miRNA-targeted oligodeoxyribonucleotide, which becomes nuclease-resistant within the conjugate design, without resort to chemically modified nucleotides. Our data presented here showed for the first time a truly catalytic character of our miR-21-miRNase and its ability to cleave miR-21 in a multiple catalytic turnover mode. We demonstrate that miRNase targeted to miR-21 (miR-21-miRNase) knocked down malignant behavior of tumor cells, including induction of apoptosis, inhibition of cell invasiveness, and retardation of tumor growth, which persisted on transplantation into mice of tumor cells treated once with miR-21-miRNase. Crucially, we discover that the high biological activity of miR-21-miRNase can be directly related not only to its truly catalytic sequence-specific cleavage of miRNA but also to its ability to recruit the non-sequence specific RNase H found in most cells to elevate catalytic turnover further. miR-21-miRNase worked synergistically even with low levels of RNase H. Estimated degradation in the presence of RNase H exceeded 103 miRNA target molecules per hour for each miR-21-miRNase molecule, which provides the potency to minimize delivery requirements to a few molecules per cell. In contrast to the comparatively high doses required for the simple steric block of antisense oligonucleotides, truly catalytic inactivation of miRNA offers more effective, irreversible, and persistent suppression of many copy target sequences. miRNase design can be readily adapted to target other pathogenic microRNAs overexpressed in many disease states.

Molecular simulations of the pistol ribozyme: unifying the interpretation of experimental data and establishing functional links with the hammerhead ribozyme.

The pistol ribozyme (Psr) is among the most recently discovered RNA enzymes and has been the subject of experiments aimed at elucidating the mechanism. Recent biochemical studies have revealed exciting clues about catalytic interactions in the active site not apparent from available crystallographic data. The present work unifies the interpretation of the existing body of structural and functional data on Psr by providing a dynamical model for the catalytically active state in solution from molecular simulation. Our results suggest that a catalytic Mg2+ ion makes inner-sphere contact with G33:N7 and outer-sphere coordination to the pro-RP of the scissile phosphate, promoting electrostatic stabilization of the dianionic transition state and neutralization of the developing charge of the leaving group through a metal-coordinated water molecule that is made more acidic by a hydrogen bond donated from the 2′OH of P32. This model is consistent with experimental activity-pH and mutagenesis data, including sensitivity to G33(7cG) and phosphorothioate substitution/metal ion rescue. The model suggests several experimentally testable predictions, including the response of cleavage activity to mutations at G42 and P32 positions in the ribozyme, and thio substitutions of the substrate in the presence of different divalent metal ions. Further, the model identifies striking similarities of Psr to the hammerhead ribozyme (HHr), including similar global fold, organization of secondary structure around an active site three-way junction, catalytic metal ion binding mode, and guanine general base. However, the specific binding mode and role of the Mg2+ ion, as well as a conserved 2′-OH in the active site, are interrelated but subtly different between the ribozymes.

Bio-inspired assembly of reduced graphene oxide by fibrin fiber to prepare multi-functional conductive bio-nanocomposites as versatile electrochemical platforms

Carbon-based bionanocomposites (CBNCs) consisting of 2D carbon nanomaterials and proteins have attracted ever-growing interests in various fields. However, current methods focus on the usage of protein monomers and preformed assemblies as building blocks directly, leaving the dynamic assembly of protein rarely explored though which may bring more flexibility for the fabrication and applications. Inspired by blood coagulation, we propose a novel method to introduce the dynamic formation of fibrin fibers for the assembly of reduced graphene oxide (rGO) to prepare multifunctional fibrin-rGO conductive CBNCs (F-G CBNCs) in a rapid, mild and one-pot way. Benefiting from the unique coagulation-mimicking assembly way and diversified properties of rGO and fibrin fibers, F-G CBNCs are endowed with high conductivity of 26.9 S m-1, as well as good formability, flexibility, mechanical strength, stability, adhesiveness to different surfaces, and electrochemical activity. Moreover, F-G CBNCs show high immobilization ability to enzymes and nanoparticles (load ratios were higher than 94%). Therefore, F-G CBNCs are elaborated as versatile conductive platforms for two modes of electrochemical catalysis and sensing with superior performance. This method may open up a new way to assemble carbon nanomaterials and fabricate high-performance bionanocomposites for diversified applications.

Catalytic pyrolysis of waste clay oil to produce high quality biofuel

In this study, waste clay oil was used as raw material to produce high quality biofuel via catalytic pyrolysis. The thermal decomposition and pyrolysis of clay oil were studied; whereas the effects of pyrolysis temperature, carrier gas flow rate, catalytic mode and catalyst to clay oil ratio on bio-oil compositions were investigated systematically. In addition, two kinds of catalyst (MCM-41 and CaO) were also used to catalyze pyrolysis of clay oil and their catalytic effects were also compared. The optimal conditions for producing high quality biofuel were under ex situ catalytic mode, carrier gas rate of 0.1 N L/min, pyrolysis temperature of 550 °C and the catalyst ratio of 1/5. Compared to MCM-41, CaO promoted the decarboxylation of waste clay oil and improved the quality of bio-oil effectively. The acid value of CaO catalytic bio-oil was much lower than that of non-catalytic bio-oil as well as that the calorific value is much higher than that of non-catalytic bio-oil and bio-diesel.