Catalytic Sequence Research Articles

A zinc-quinone battery for paired hydrogen peroxide electrosynthesis

Hydrogen peroxide is a commodity chemical with immense applications as an environmentally benign disinfectant for water remediation, a green oxidant for synthetic chemistry and pulp bleaching, an energy carrier molecule and a rocket propellant. It is typically synthesized by indirect batch anthraquinone process, where sequential hydrogenation and oxidation of anthraquinone molecules generates H2O2. This highly energy demanding catalytic sequence necessitates the advent of new reaction pathways with lower energy expenditure. Here we demonstrate a Zn-quinone battery for paired H2O2 electrosynthesis at the three phase boundary of its cathodic half-cell during electric power generation. The catalytic quinone half-cell of the Zn-quinone battery, mediates proton coupled electron transfer with molecular oxygen during its chemical regeneration thereby pairing peroxide electrosynthesis with electricity generation. Hydrogen peroxide synthesizing Zn-quinone battery (HPSB) demonstrated a peak power density of ~90 mW/cm2 at a peak current density of ~145 mA/cm2 while synthesizing ~230 mM of H2O2. HPSB offers immense opportunities as it distinctly couples electric power generation with peroxide electrosynthesis which in-turn transforms energy conversion in batteries truly multifunctional.

DNAzyme-dependent Analysis of rRNA 2'-O-Methylation.

Guide box C/D small nucleolar RNAs (snoRNAs) catalyze 2'-O-methylation of ribosomal and small nuclear RNA. However, a large number of snoRNA in higher eukaryotes may promiscuously recognize other RNA species and 2'-O-methylate multiple targets. Here, we provide step-by-step guide for the fast and non-expensive analysis of the site-specific 2'-O-methylation using a well-established method employing short DNA oligonucleotides called DNAzymes. These DNA fragments contain catalytic sequences which cleave RNA at specific consensus positions, as well as variable homology arms directing DNAzyme to its RNA targets. DNAzyme activity is inhibited by 2-'O-methylation of the nucleotide adjacent to the cleavage site in the RNA. Thus, DNAzymes, limited only by the consensus of the cleaved sequence, are perfect tools for the quick analysis of snoRNA-mediated RNA 2'-O-methylation. We analyzed snoRNA snR13- and snR47-guided 2'-O-methylation of 25S ribosomal RNA in Saccharomyces cerevisiae to demonstrate the simplicity of the technique and to provide a detailed protocol for the DNAzyme-dependent assay.

Albicidin, a potent DNA gyrase inhibitor with clinical potential.

The emergence of multiple antibiotic-resistant bacteria is a serious global problem which requires the development of new effective antimicrobial therapeutics. Albicidin produced by the sugarcane pathogen Xanthomonas albilineans is a potent DNA gyrase inhibitor with inhibitory effects significantly better than most DNA gyrase inhibitors. Albicidin acts primarily by inhibiting the religation of the cleaved DNA intermediate during the gyrase catalytic sequence similar to quinolones. The clinical realization of albicidin has been hampered by limited production and its unsolved structure. In this review, the relationship between albicidin and sugarcane leaf-scald disease is described. Furthermore, the biosynthesis and resistance mechanisms of albicidin are discussed. Finally, recent efforts to solve the structure and produce albicidin in a heterologous host and chemically are summarized.

Gold‐catalyzed [4+2] Annulations of Dienes with Nitrosoarenes as 4 π Donors: Nitroso‐Povarov Reactions

AbstractThis work reports the first success of the nitroso‐Povarov reaction, involving gold‐catalyzed [4+2] annulations of nitrsoarenes with substituted cyclopentadienes. In this catalytic sequence, nitrosoarenes presumably attack gold‐π‐dienes by a 1,4‐addition pathway, generating allylgold nitrosonium intermediates to complete an intramolecular cyclization. Acyclic dienes are also applicable substrates, and affording oxidative nitroso‐Povarov products.

Gold-catalyzed [4+2] Annulations of Dienes with Nitrosoarenes as 4 π Donors: Nitroso-Povarov Reactions.

This work reports the first success of the nitroso-Povarov reaction, involving gold-catalyzed [4+2] annulations of nitrsoarenes with substituted cyclopentadienes. In this catalytic sequence, nitrosoarenes presumably attack gold-π-dienes by a 1,4-addition pathway, generating allylgold nitrosonium intermediates to complete an intramolecular cyclization. Acyclic dienes are also applicable substrates, and affording oxidative nitroso-Povarov products.

Theoretical Investigation of Regioselectivity in the Rh‐Catalyzed Coupling Reaction of 3‐Phenylthiophene with Styrene

The regioselectivity of the Rh‐catalyzed coupling reaction of 3‐phenylthiophene with styrene was investigated by quantum chemistry calculations. Previous experimental studies showed that styrene selectively couples to the phenyl moiety of the phenylthiophene in the coupling reaction. In this work, possible reaction paths for the coupling were evaluated using theoretical calculations, and the most energetically reasonable catalytic sequence was found to be the following: (1) The Rh catalyst cleaves two C–H bonds on the phenyl and thiophene moieties, leading to a five‐membered rhodacycle intermediate. (2) Styrene is inserted into the C–Rh bond on the phenyl group of the rhodacycle. (3) Then, β‐hydrogen elimination occurs to form 2′‐alkenylated 3‐phenylthiophene. Natural bond orbital analysis results suggest that the key product‐determining step, i.e., the preferential insertion of styrene to the phenyl side (2), occurs due to the difference in π‐electron density between the phenyl and thienyl groups of the five‐membered rhodacycle intermediate.

Synthesis of Structurally Diverse 3-, 4-, 5-, and 6-Membered Heterocycles from Diisopropyl Iminomalonates and Soft C-Nucleophiles.

Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl- and N-aryl-substituted diisopropyl iminomalonates and a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, and tetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.

A new insight into catalytic role of copper sulfate on elemental mercury oxidation: DFT and experimental study

Copper sulfate (CuSO4) is a ubiquitous component in natural minerals and industrial dusts. However, CuSO4 has been believed usually that it has adverse effect on elemental mercury (Hg0) removal from flue gas. Here, we offered a new insight into the effect of crystal water in copper sulfate on Hg0 catalytic oxidation. The structure evolution of copper sulfate by density functional theory (DFT) calculation revealed anhydrous CuSO4 crystal contributing to a better HCl adsorption which provided a precondition for Hg0 oxidation. Experimental results about the catalytic activity sequence of CuSO4 > CuSO4·H2O > CuSO4·5H2O with HCl confirmed the negative effect of crystal water on Hg0 catalytic oxidation. To realize industrial application, supported catalysts CuSO4/α-Al2O3 synthesized by wet impregnation method was employed for elemental mercury (Hg0) oxidation and the results exhibited excellent performance in Hg0 oxidation under 250 °C–400 °C. The Hg0 conversion efficiency was above 97% in the presence of 2 ppm HCl + 6% O2 at 300 °C. Combining computational and X-ray photoelectron spectroscopy (XPS) analyses together, Cu atoms exposure on the surface of anhydrous CuSO4 were the critical active sites for Hg0 oxidation and the reaction obeyed the Eley–Rideal mechanism.

Ternary complexes containing Copper(II), l-Valinate and α, ά-bipyridyl or 1,10-phenanthroline: Synthesis, characterization, ligand substitution and oxidase biomimetic catalytic activity studies

Ternary copper(II) complexes with the molecular formulae of [CuIILL′]X or [CuIILL′X]; L = l-Valinate; L′ = α, ά-bipyridyl or 1,10 - phenanthroline and X is Cl¯, Br¯, NO3¯, AcO¯, ½SO42− or ClO4¯ were synthesized. Elemental and thermal analysis in addition to electrochemical (molar conductance and cyclic voltammetry), magnetic moment measurements as well spectral (FT-IR, UV–Vis and ESR) techniques were used to characterize the complexes. The spectroscopic results suggested square pyramidal and square planar geometries for the five- and four-coordinate complexes respectively. Powder X-ray diffraction spectral data along with the structure solution program Expo 2014 has been used for structural elucidation of the sulfato complexes 1 and 5. Stopped follow technique was employed to study the substitution of the nonelectrolytic coordinately counter anion ligand by using thiourea (TU) as a function of nucleophile and a biphasic process is proposed. An initial fast reaction is followed by a slower one and the initial one was found to be counter ion dependent. Bio-mimicking the multicopper oxidase enzyme such as catechol oxidase and phenoxazinone synthase is a further goal of the present study. Catalytic examinations displayed that the present complexes are promising candidates as functional mimic of the examined enzymes and the probable mechanistic catalytic sequences are discussed.

Sir2D, a Sirtuin family protein, regulates adenylate cyclase A expression through interaction with the MybB transcription factor early in Dictyostelium development upon starvation

Sirtuin interacts with many regulatory proteins involved in energy homeostasis, DNA repair, cell survival, and lifespan extension. We investigated the functional roles of Sir2D during early Dictyostelium development upon starvation. We found that ectopic expression of Sir2D accelerated development among three Sirtuins containing highly homologous catalytic domain sequences to mouse Sirt1. Sir2D expression upregulated adenylate cyclase A (aca) mRNA expression 2, 4 and 6 h after starvation. We have previously reported that nicotinamide, a Sirt1 inhibitor, treatment delayed the development and decreased the expression of aca at 4 h after starvation. Sir2D expressing cells showed resistance against the nicotinamide effect. RNAi-mediated Sir2D knockdown cells were generated, and their development was also delayed. Aca expression was decreased 4 h after starvation. Sir2D expression restored the developmental impairment of Sir2D knockdown cells. The induction of aca upon starvation starts with transcriptional activation of MybB. The ectopic expression of MybB accelerated the development and increased the expression of aca 2 and 4 h after starvation but did not restore the phenotype of Sir2D knockdown cells. Sir2D expression had no effects on MybB-null mutant cells during early development. Thus, MybB is necessary for the upregulation of aca by Sir2D, and Sir2D is necessary for the full induction of aca after 4 h by MybB. MybB was coimmunoprecipitated with Sir2D, suggesting an interaction between MybB and Sir2D. These results suggest that Sir2D regulates aca expression through interaction with the MybB transcription factor early in Dictyostelium development upon starvation.

Rare-earth metal catalysts for alkene hydrosilylation

Rare-earth metal catalyzed hydrosilylation of alkenes has emerged as a powerful and selective strategy for the synthesis of organosilanes. This transformation can offer distinctive catalytic sequences and reaction patterns from other catalysts because of the high electropositivity and lack of oxidative-addition process of rare-earth metal. This review summarizes the rare-earth metal catalysts for hydrosilylation of alkene according to the type of ligands. The synthesis and structure of rare-earth metal catalysts, the substrate scope as well as some preliminary structure-activity relationship and mechanism are discussed.

Selectivity in Ring‐Closing Metathesis: Synthesis of Propellanes and Angular Aza‐tricycles

AbstractSeveral naturally occurring alkaloids contain quaternary carbon centers attached to a nitrogen atom. An efficient synthetic protocol has been developed to assemble indoline‐fused propellanes over aza‐tricyclic carbazole derivatives via a selective ring‐closing metathesis employing Grubbs’ first‐generation catalyst. Electronic factors seem to play a critical role in the outcomes. The structure of propellanes and angular aza‐tricyclic compounds are confirmed by catalytic hydrogenation sequence. To expand the synthetic utility of these propellanes and aza‐tricycles, Suzuki‐Miyaura cross‐coupling reaction has been employed to generate functionalized polycycles. Fourteen ruthenium carbene catalysts are examined to synthesize propellanes and aza‐tricycles.magnified image

Optimized Catalytic Bleaching Sequences for Eucalyptus Kraft Pulp

Contemporary multi-stage bleaching processes partially remove residual lignin and hexenuronic acid from cellulosic pulps. The reactions in the steps could be faster and consume smaller amounts of chemicals. Catalytic bleaching (Hcat), utilizing hypochlorite (H), triethylenediamine (DABCO) and its derivative N-carboxymethyl triethylenediamine (CM-DABCO), is a new discovery that has the potential to improve the chemical and energetic efficiency of bleaching processes in chemical pulp mills, e.g. through reducing the reaction time of the bleaching processes. The objective of this study was to clarify if new kraft pulp bleaching sequences with initial stage of chlorine dioxide (ClO2; D) and an intermediate stage of Hcat could provide fully bleached pulps. The bleaching sequences of the studied eucalyptus pulps include D0E(OP)Hcat(Q)P and HcatZ/DP, which attained a final brightness of 88 and 89% ISO, respectively. HcatZ/DP showed to be the best sequence for the catalytic bleaching of eucalyptus kraft pulps. This study may open new doors to future bleaching of cellulose pulps with fewer towers and decreased use of chemicals.

Results supporting the concept of the oxidant-mediated protein amino acid conversion, a naturally occurring protein engineering process, in human cells.

Reactive oxygen species (ROS) play an important role in the development of various pathological conditions as well as aging. ROS oxidize DNA, proteins, lipids, and small molecules. Carbonylation is one mode of protein oxidation that occurs in response to the iron-catalyzed, hydrogen peroxide-dependent oxidation of amino acid side chains. Although carbonylated proteins are generally believed to be eliminated through degradation, we previously discovered the protein de-carbonylation mechanism, in which the formed carbonyl groups are chemically eliminated without proteins being degraded. Major amino acid residues that are susceptible to carbonylation include proline and arginine, both of which are oxidized to become glutamyl semialdehyde, which contains a carbonyl group. The further oxidation of glutamyl semialdehyde produces glutamic acid. Thus, we hypothesize that through the ROS-mediated formation of glutamyl semialdehyde, the proline, arginine, and glutamic acid residues within the protein structure can be converted to each other. Mass spectrometry provided results supporting that proline 45 (a well-conserved residue within the catalytic sequence) of the peroxiredoxin 6 molecule may be converted into glutamic acid in cultured human cells, opening up a revolutionizing concept that biological oxidation elicits the naturally occurring protein engineering process.

Results supporting the concept of the oxidant-mediated protein amino acid conversion, a naturally occurring protein engineering process, in human cells

Reactive oxygen species (ROS) play an important role in the development of various pathological conditions as well as aging. ROS oxidize DNA, proteins, lipids, and small molecules. Carbonylation is one mode of protein oxidation that occurs in response to the iron-catalyzed, hydrogen peroxide-dependent oxidation of amino acid side chains. Although carbonylated proteins are generally believed to be eliminated through degradation, we previously discovered the protein de-carbonylation mechanism, in which the formed carbonyl groups are chemically eliminated without proteins being degraded. Major amino acid residues that are susceptible to carbonylation include proline and arginine, both of which are oxidized to become glutamyl semialdehyde, which contains a carbonyl group. The further oxidation of glutamyl semialdehyde produces glutamic acid. Thus, we hypothesize that through the ROS-mediated formation of glutamyl semialdehyde, the proline, arginine, and glutamic acid residues within the protein structure can be converted to each other. Mass spectrometry provided results supporting that proline 45 (a well-conserved residue within the catalytic sequence) of the peroxiredoxin 6 molecule may be converted into glutamic acid in cultured human cells, opening up a revolutionizing concept that biological oxidation elicits the naturally occurring protein engineering process.

Yolk-Shell-Mesostructured Silica-Supported Dual Molecular Catalyst for Enantioselective Tandem Reactions.

Yolk-shell-mesostructured silica was used as a support in the development of an active-site-isolated bifunctional catalyst that can mediate a sequential organic transformation. Herein, through immobilization, the location of two catalytic species is controlled: a base functionality is anchored in the channels of the outer silica shell and a chiral ruthenium/diamine functionality is anchored on the inner silica yolk. The result is a yolk-shell-mesostructured silica-supported active-site-isolated dual molecule catalyst. Structural analysis through solid-state carbon 13 C NMR spectroscopy reveals its well-defined single-site dual active centers. Electron microscopy investigations disclose its uniformly distributed mesoporous nanoparticles. As envisaged, this bifunctional catalyst enables a controllable aza-Michael addition/asymmetric transfer hydrogenation catalytic sequence, where the base-catalyzed aza-Michael addition of enones and amines to aryl-substituted -secondary amino ketones is followed by a Ru-catalyzed asymmetric transfer hydrogenation. Various aryl-substituted γ-secondary amino alcohols are obtained in high yields and enantioselectivities via this one-pot enantioselective organic transformation. Furthermore, the heterogeneous catalyst can be applied in a continuous-flow process, which was shown to be particularly attractive for the practical preparation of aryl-substituted γ-secondary amino alcohols in an environmentally friendly medium.

The evolutionary dynamics of metabolic protocells.

Protocell multilevel selection models have been proposed to study the evolutionary dynamics of vesicles encapsulating a set of replicating, competing and mutating sequences. The frequency of the different sequence types determines protocell survival through a fitness function. One of the defining features of these models is the genetic load generated when the protocell divides and its sequences are assorted between the offspring vesicles. However, these stochastic assortment effects disappear when the redundancy of each sequence type is sufficiently high. The fitness dependence of the vesicle with its sequence content is usually defined without considering a realistic account on how the lower level dynamics would specify the protocell fitness. Here, we present a protocell model with a fitness function determined by the output flux of a simple metabolic network with the aim of understanding how the evolution of both kinetic and topological features of metabolism would have been constrained by the particularities of the protocell evolutionary dynamics. In our model, the sequences inside the vesicle are both the carriers of information and Michaelis-Menten catalysts exhibiting saturation. We found that the saturation of the catalysts controlling the metabolic fluxes, achievable by modifying the kinetic or stoichiometric parameters, provides a mechanism to ameliorate the assortment load by increasing the redundancy of the catalytic sequences required to achieve the maximum flux. Regarding the network architecture, we conclude that combinations of parallel network motifs and bimolecular catalysts are a robust way to increase the complexity of the metabolism enclosed by the protocell.

Dual Catalytic Synthesis of Antiviral Compounds Based on Metallocarbene-Azide Cascade Chemistry.

Aryl azides trap ortho-metallocarbene intermediates to generate indolenones possessing a reactive C-acylimine moiety, which can react with added indole nucleophiles to afford the 2-(3-indolyl)indolin-3-one scaffold found in the antiviral natural product isatisine A. This overall process occurs through a dual catalytic sequence at room temperature. Redox activation of the Cu(OTf)2 precatalyst by indole results in catalytically competent Cu(I) required for azide-metallocarbene coupling. The Brønsted acid that is also formed from Cu(OTf)2 reduction is responsible for catalysis of the C-C bond-forming indole addition step. This modular, procedurally simple method allows for rapid assembly of bis(indole) libraries, several of which proved to have anti-infective activity against respiratory syncytial virus and Zika virus.

Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA.

NadA is a multifunctional enzyme that condenses dihydroxyacetone phosphate (DHAP) with iminoaspartate (IA) to generate quinolinic acid (QA), the universal precursor of the nicotinamide adenine dinucleotide (NAD(P)) cofactor. Using X-ray crystallography, we have (i) characterized two of the reaction intermediates of QA synthesis using a "pH-shift" approach and a slowly reacting Thermotoga maritima NadA variant and (ii) observed the QA product, resulting from the degradation of an intermediate analogue, bound close to the entrance of a long tunnel leading to the solvent medium. We have also used molecular docking to propose a condensation mechanism between DHAP and IA based on two previously published Pyrococcus horikoshi NadA structures. The combination of reported data and our new results provide a structure-based complete catalytic sequence of QA synthesis by NadA.

Synergistic effect of (RuCl 3 + IrCl 3 ) catalyzed oxidative conversion of rizatriptan benzoate to rizatriptan-N-oxide with N-haloamine: Exploration of scope, reaction behavior and kinetic data

Abstract Synergistic effect of (RuCl3 + IrCl3) as a binary mixture and alone have been investigated in the oxidation of rizatriptan benzoate (RTB) with chloramine-T (CAT) in aqueous HClO4 medium at 303 K. The kinetic patterns were found to be different in all the three catalyzed reactions. Activation parameters have been calculated. Under the identical set of experimental conditions, the reaction rate reveals that all the three catalyzed reactions are about 25 to 75-fold faster than the uncatalyzed reactions. The observed catalytic reaction rate sequence follows the order: (RuCl3 + IrCl3) > IrCl3 > RuCl3. The observed reactivity sequence may be attributed due to the fact that IrCl3–Carbon σ complexes are less strong, less localized and less covalent than RuCl3–Carbon complexes. Consequently, the present redox system is of great importance as the drug rizatriptan is transformed into rizatriptan-N-oxide On the basis of kinetic data, most plausible mechanisms were proposed.