N-oxide Research Articles

Replacement of Tyrosines by Unnatural Amino Acid Aminophenylalanine Leads to Metal-Mediated Aniline Free Radical Formation in a Copper Amine Oxidase.

Copper amine oxidases (CAOs) catalyze the oxidative deamination of primary amines to aldehyde, ammonia, and hydrogen peroxide as products and are widely distributed in bacteria, plants, and eukaryotes. These enzymes initiate the single turnover, post-translational conversion of an active site tyrosine to the redox cofactor 2,4,5-trihydroxyphenylalanine quinone (TPQ), subsequently employing TPQ to catalyze steady-state amine oxidation. The mechanisms of TPQ biogenesis and steady-state amine oxidation have been studied extensively, with consensus mechanisms proposed for both reactions. One unresolved issue has been whether the Cu2+ center must undergo formal reduction to Cu1+ in the course of the reaction. Herein, we investigate the properties of the active site of a yeast (Hansenula polymorpha) amine oxidase (HPAO) that has undergone site-specific insertion of a para-aminophenylalanine (pAF) into the position of either the precursor tyrosine to TPQ (Y405) or the two strictly conserved neighboring tyrosines (Y305 and Y407). While our original intention was to interrogate cofactor biogenesis using a precursor unnatural amino acid (UAA) of altered redox potential and pKa, we instead observe an unanticipated reaction assigned to an intramolecular electron transfer from pAF to the active site copper ion. We establish the generality of the observed active site chemistry using exogenously added, aniline-containing substrates under conditions that prevent side chain amine oxidation. The results support previous proposals that the activation of the TPQ precursor occurs in the absence of a formal valence change at the active site copper site. The described reaction of pAFs with the active site redox Cu2+ center of HPAO provides a prototype for either the engineering of the enzymatic oxidation of exogenous anilines or the insertion of site-specific free radical probes within proteins.

α-Synuclein Overexpression and the Microbiome Shape the Gut and Brain Metabolome in Mice.

Pathological forms of the protein α-synuclein contribute to a family of disorders termed synucleinopathies, which includes Parkinson's disease (PD). Most cases of PD are believed to arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms and pathology in animal models. To explore how the microbiome may impact PD-associated genetic risks, we quantitatively profiled nearly 630 metabolites from 26 biochemical classes in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice with or without microbiota. We observe tissue-specific changes driven by genotype, microbiome, and their interaction. Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. Notably, levels of the microbial metabolite trimethylamine N-oxide (TMAO) strongly correlate from the gut to the plasma to the brain, identifying a product of gene-environment interactions that may influence PD-like outcomes in mice. TMAO is elevated in the blood and cerebral spinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and the microbiome in a mouse model of PD.

Biocatalytic Oxidative Amination of para‐Substituted Phenols

AbstractBiocatalytic preparation of chiral amines is a large and burgeoning field in organic chemistry. Many enzymes and routes have been published, including transaminases, imine reductases, reductive aminases, amine dehydrogenases and others. However, all these routes rely on some sacrificial substrate, in the form of either amine donor or cofactor regeneration substrate. Herein, we report the direct oxidative amination of p‐substituted phenols catalyzed by an evolved flavoprotein oxidase, with the consumption of only substrate and O2, and release of H2O2. The substrate scope of the reaction is studied, and is tolerant of a diverse panel including ammonia, primary and secondary amines, and amino acids. The reaction is later employed at preparative scale to generate aminated products in 50–80 % yield. This report establishes flavoprotein oxidase as a new and economical member of the chemist's toolkit for biocatalytic generation of chiral amines, acting as oxidative aminase.

Porous S-doped carbon nitride foam with accelerated charge dynamics for synchronous photocatalytic hydrogen production and highly selective oxidation of amines

Porous S-doped carbon nitride foam with accelerated charge dynamics for synchronous photocatalytic hydrogen production and highly selective oxidation of amines

Artificial Spores as Multi‐Functional Biocatalysts to Perform Biosynthetic Cascades

AbstractCells exhibit diverse structural formations such as biofilms and spores, enabling them to acquire novel functionalities. Many of these structures display biomacromolecules, including enzymes, tethered to cell walls to support various extracellular processes. Alternatively, encapsulating single cells with polymer coatings offers a strategy that circumvents the need for genetic engineering while imparting artificial functionalities to cells. Here, a universal method is presented for encapsulating single gram‐negative microbes with polymeric coatings based on the ancestral gall ink formed by tannic acid‐iron complexes. As a result, synthetic spores are achieved that selectively bind His‐tagged enzymes through the formation of unprecedented galloyl/imidazole‐Fe2+ complexes via ligand substitution demonstrated by density functional theory. These synthetic spores with a thickness of 41.5 ± 4.2 nm and a stiffness of 6.0 ± 3.5 GPa serve as biocatalytic materials for the one‐pot oxidative amination of diols into amino alcohols, facilitated by the cooperative catalysis between intracellular endogenous or recombinant oxidoreductases, and an extracellular transaminase from Pseudomonas fluorescens displayed at the spore surface. These spores maintain their performance in three consecutive batch cycles. Integrating isolated enzymes onto the surface of engineered microbes coated with polymers offers novel opportunities for synthetic biology, advancing the efficiency of biosynthetic cascades in solid‐state environments.

Heterogeneous catalytic aerobic oxidation of primary amines to amides using unsupported nanoporous palladium catalyst

An efficient and highly selective heterogeneous catalyst system for aerobic oxidation of primary amines was developed using unsupported palladium nanopores (PdNPore). A variety of aromatic, aliphatic, and heterocyclic primary amines were oxidized to the corresponding amides in satisfactory to excellent yields using ambient air as an oxidant. No palladium was leached from PdNPore during the oxidation reaction. The catalyst could be readily recovered and reused without a decrease in catalytic activity. The kinetic studies and control experiments demonstrated that nitrile acts as an intermediate, which undergo hydration to afford amide as the final product.

CO2 photoreduction integrated with oxidative coupling of amines over WO3/Cu(BTC) nanocomposite

Here, we report an efficient integrated CO2 photoreduction to methanol accompanied with the simultaneous oxidation of benzyl amines to corresponding imines using quadrangular WO3 nanoplates grafted with Cu(BTC) as a photocatalyst under visible light, enabling to provide efficient use of the photogenerated electrons and holes. Under the optimized reaction conditions, the maximum yield of methanol and N-(4-methoxybenzyl)-1-(4-methoxyphenyl)methanimine was found to be 642 μmol-g−1 and 98 %, respectively. The developed integrated dual functional system comprising CO2 reduction coupled with the oxidative organic synthesis opens a new window for value chain up gradation at both ends using sustainable solar energy.

Optimization studies on laccase activity of Proteus mirabilis isolated from treatment sludge of textile industry factories : Optimization of laccase activity of Proteus mirabilis.

Laccase is an exothermic enzyme with copper in its structure and has an important role in biodegradation by providing oxidation of phenolic compounds and aromatic amines and decomposing lignin. The aim of this study is to reach maximum laccase enzyme activity with minimum cost and energy through optimization studies of Proteusmirabilis isolated from treatment sludge of a textile factory. In order to increase the laccase enzyme activities of the isolates, medium and culture conditions were optimized with the study of carbon (Glucose, Fructose, Sodium Acetate, Carboxymethylcellulose, Xylose) and nitrogen sources (Potassium nitrate, Yeast Extract, Peptone From Soybean, Bacteriological Peptone), incubation time, pH, temperature and Copper(II) sulfate concentration then according to the results obtained. Response Surface Method (RSM) was performed on six different variables with three level. According to the data obtained from the RSM, the maximum laccase enzyme activity is reached at pH 7.77, temperature 30.03oC, 0.5g/L CuSO4, 0.5g/L fructose and 0.082g/L yeast extract conditions. After all, the laccase activity increased 2.7 times. As a result, laccase activity of P. mirabilis can be increased by optimization studies. The information obtained as a result of the literature studies is that the laccase enzymes produced in laboratory and industrial scale are costly and their amounts are low. This study is important in terms of obtaining more laccase activity from P.mirabilis with less cost and energy.

Heterogeneous Organocatalysts for Light-Driven Reactions in Continuous Flow.

Within the realm of organic synthesis, photocatalysis has blossomed since the beginning of the last decade. A plethora of classical reactivities, such as selective oxidation of alcohol and amines, redox radical formation of reactive species in situ, and indirect activation of an organic substrate for cycloaddition by EnT, have been revised in a milder and more sustainable fashion via photocatalysis. However, even though the spark of creativity leads scientists to explore new reactions and reactivities, the urgency of replacing the toxic and critical metals that are involved as catalysts has encouraged chemists to find alternatives in the branch of science called organocatalysis. Unfortunately, replacing metal catalysts with organic analogues can be too expensive sometimes; however, this drawback can be solved by the reutilization of the catalyst if it is heterogeneous. The aim of this review is to present the recent works in the field of heterogeneous photocatalysis, applied to organic synthesis, enabled by continuous flow. In detail, among the heterogeneous catalysts, g-CN, polymeric photoactive materials, and supported molecular catalysts have been discussed within their specific sections, rather than focusing on the types of reactions.

Copper Phenylacetylide and TiO2 Modification for an Efficient Visible-Light-Driven Oxidative Coupling of Amines.

The selective oxidation of amines to imines under mild conditions has attracted much attention. Our study reveals that copper phenylacetylide (PhC2Cu) could serve as an efficient photocatalyst for imine synthesis under visible-light irradiation (>400 nm). Utilizing benzylamine as a model reactant, PhC2Cu achieves an imine yield of 50.4%, which is 5 times higher than that of P25 under the same conditions and comparable to the yield obtained by the 3 wt % Au/P25 photocatalyst (55.4%). Further loading 3.9 nm TiO2 onto PhC2Cu through tetrabutyl titanate hydrolysis increases the imine yield to 84.7%, with a Ti:Cu atomic ratio of 3.65%. Control experiments, photoluminescence (PL) spectra, optical pump terahertz probe (OPTP) spectra, and electron spin resonance (ESR) tests confirm that the optimized TiO2 modification promotes the separation of excited carriers and electron transfer in PhC2Cu and facilitates the activation of surface oxygen, thereby enhancing the formation of superoxide radicals, a key active oxygen species in the reaction system. This work presents a promising strategy for efficient imine synthesis via amine coupling and expands the application field of PhC2Cu-based photocatalysts.

Oxidimetric determination of Cetirizine and Levocetirizine in tablets using Oxone

This work is aimed at studying the kinetics of Cetirizine (CTZ) and Levocetirizine(L-Cet) oxidation by potassium hydrogen peroxomonosulfate (PMS) in the form of Oxone and developing an analytical method for their quantitative determination. The required amount of CTZ and L-Cet was dissolved in double distilled water, pH buffer solution and PMS solution were added. After 1.5min, the solution was acidified. The excess PMS was iodometrically titrated applying visual end-point detection approach. The reaction was studied in aqueous media at 293 K and over pH range 7.0 to 10.0. The second order rate constants, k (L mol−1 min−1) has been calculated from kinetic data. A suitable scheme has been proposed for the oxidation of CTZ and L-Cet with PMS, which shows electrophilic attack of the monoanion of PMS on a nitrogen atom of the analyzed compounds with the formation of the corresponding amine oxides. CTZ and L-Cet were determined by indirect titration with PMS. The recovery of the assayed analytes in tablets ranged from 99.4 to 101.0%. A paired t-test showed that all results obtained for CTZ and L-Cet in model solutions and dosage form of Levocetirizine (5mg) and Сetirizine (10mg) tablets, using the proposed procedure and the official procedure respectively, were in consonance at the 95 % confidence level, (х ̅ -μ) 100/μ < RSD. Techniques have been developed and the possibility of quantitative determination of Levocetirizine and Cetirizine in substance and tablet forms using Oxone as an analytical reagent has been demonstrated.

Metal-free Oxidations with m-CPBA: An Octennial Update

Abstract: meta-Chloroperbenzoic acid (mCPBA) is a readily available peroxide that is a powerful oxidizing agent utilized in a range of oxidative reactions. Metal-free oxidations mediated by mCPBA involving selective oxidation of aliphatic amines to oximes, selective oxidation of organosulphides/ aldehydes, synthesis of heterocyclic N-oxides, domino C[sp2] hydroxylation/ annulation of enaminones (heterocyclic ring formation), acid to phenol conversion, oxidation of exocyclic C=C bond, oxidative ring contraction, etc. have been comprehensively and critically examined in this mini-review from 2015 to date.

Tandem Electrochemical Oxidation of Polycyclic Aromatic Amines Towards Carbazoles and Phenazine-based Aza-helicenes.

Experimental and theoretical study of the regioselectivity and mechanism of polycyclic aromatic amine (PAA) electrochemical oxidation is important for designing nitrogen doped large π-conjugated functional molecules. Herein, we used binary-, ternary-, and quaternary-fused PAAs as electro-oxidative reaction substrates to investigate the yield changes of carbazole and phenazine based aza-helicene other than oligomers, which were obtained through pyrrole and pyrazine annulation pathways. Combined with the restrained electrostatic potential (RESP) and steric hindrance factor analysis of the substrate, the electron spin density distribution of free radical resonance hybrid and the spin population analysis of the atoms in the structure of each free radical tautomer indicate that the degree of delocalized dispersion of N free radical and the resulting change in the spin density distribution of C free radical tautomers determine the reaction regioselectivity. The potential charge of the K-region, Bay-region, and L-region adjacent to the C(α)-C(β1) bond is higher than that of other regions within the molecule, and the charge in these high RESP regions tends to delocalize more strongly toward electron-deficient N free radicals. Thus, the activity of N-C(α)-C(β1) region is increased, which supports the proposed free radical addition and free radical coupling mechanism for the electro-oxidative reaction of PAA.

Why Does Monoamine Oxidase (MAO) Catalyze the Oxidation of Some Tetrahydropyridines?

Results pertaining to the mechanism of the oxidation of the tertiary amine 1-methyl-4-(1-methyl-1-H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (MMTP, a close analog of the Parkinsonism inducing compound MPTP) by 3-methyllumiflavin (3MLF), a chemical model for the FAD cofactor of monoamine oxidase, are reported. MMTP and related compounds are among the few tertiary amines that are monoamine oxidase B (MAO-B) substrates. The MMTP/3MLF reaction is catalytic in the presence of O2 and the results under anaerobic conditions strongly suggest the involvement of radical intermediates, consistent with a single electron transfer mechanism. These observations support a new hypothesis to explain the MAO-catalyzed oxidations of amines. In general, electron transfer is thermodynamically unfavorable, and as a result, most 1° and 2° amines react via one of the currently accepted polar pathways. Steric constraints prevent 3° amines from reacting via a polar pathway. Those select 3° amines that are MAO substrates possess certain structural features (e. g., a C-H bond that is α- both to nitrogen and a C=C) that dramatically lower the pKa of the corresponding radical cation. Consequently, the thermodynamically unfavorable electron transfer equilibrium is driven towards products by an extremely favorable deprotonation step in the context of Le Chatelier's principle.

Polyaryl sulfone amine oxide membranes with adjustable pore and interesting “trade-off” effect

Creating advanced polymer membranes with adjustable pores for various separation methods has been challenging because of the lack of new materials with adaptable and reversible chemical structures. In this study, we designed membranes using polyarylene ether sulfone/amide tertiary amine (PAES/ATA) copolymerized with polyarylene ether sulfone and polyamide tertiary amine. These membranes incorporated amine oxide units into their molecular chains by oxidizing the TA unit in the PAES/ATA copolymer chain. Applying the oxidation process improved antifouling properties, with the oxidized membrane showing a permeance recovery rate (Frr) of 95.48 % and a total fouling ratio (Rt) of 9.35 %. These units also functioned as switches, altering their charge in different pH environments, thereby allowing pore size adjustment in the membranes. Notably, with the formation of amine oxide, these membranes exhibited properties distinct from the traditional “trade-off” effect, which is a persistent challenge in membrane technology development. The permeance and rejection rate of these membranes demonstrated the “simultaneous rise phenomenon” following a facile oxidation treatment to form amine oxide. This study presents a novel approach to develop membranes with new functional and tunable filtration capabilities, potentially applicable in various separation processes.

The insertion of thiazolo[5,4-d]thiazole unit in covalent triazine framework for boosting the photocatalytic capacities in both selective aerobic oxidation of sulfides and amines

Recently, covalent triazine frameworks (CTFs) have realized versatile applications in the field of photocatalysis. Herein, two CTFs photocatalysts were designed and synthesized with or without thiazolo[5,4-d]thiazole (TzTz), an electron deficient unit, to highlight the introduction of an additional acceptor unit on the photocatalytic aerobic oxidation reaction of triazine based CTFs. Specifically, CTF-TZDA was prepared by a condensation reaction between terephthalimidamide and 4,4′-(thiazolo[5,4-d]thiazole-2,5-diyl) dibenzaldehyde (TzTz aldehyde), and similarly, CTF-FPBA was prepared between terephthalimidamide and [1,1′-biphenyl]-4,4′-dicarbaldehyde. CTF-TZDA showed high photocatalytic activities towards aerobic oxidation of both benzyl sulfides and benzyl amines to benzyl sulfoxides and benzyl imines, respectively, and the reaction was powered by blue light. A wide range of substrates can be aerobically oxidized with high yield (about 99%) and high selectivity over CTF-TZDA photocatalyst. The insertion of the TzTz unit lowered that band gap, accelerated the delocalization of π electrons, and elevated the LUMO levels of CTF-TZDA, which are beneficial to extend the light absorption range, and to promote the separation and transfer of photo-induced charge carriers. This work indicates that the insertion of an additional electron deficient unit rich in heteroatoms is considered as a feasible approach towards enhancing the photocatalytic activity of CTFs.

Deciphering the Role of Nickel in Electrochemical Organic Oxidation Reactions

AbstractOrganic oxidation reactions (OORs) powered by renewable energy sources are gaining importance as a favorable alternative to oxygen evolution reaction, with the promise of reducing the cell potential and enhancing the overall viability of the water electrolysis. This comprehensive review delves into the electrochemical oxidation of diverse organic compounds, including alcohols, aldehydes, amines, and urea, as well as biomass‐derived renewable feedstocks such as hydroxymethylfurfural and glycerol. The key focus centers on the role of nickel (Ni)‐based catalysts for these OORs. The unique redox activity and chemical nature of Ni have been proven instrumental for the sustainable and cost‐effective oxidation of various organic molecules more efficiently and selectively. This review article discusses how strategic choices, such as the selection of foreign metals, intercalating species, vacancies, defects, and a secondary element (e.g. chalcogens and non‐metals), contribute to tuning the electrochemical performances of a Ni‐based (pre)catalyst for OORs. Moreover, this review provides insights into the active species in various reaction environments and further explores reaction mechanisms, to apparent phase changes of the catalyst with the most relevant examples. Finally, the review not only elucidates the limitations of the current approaches but also outlines potential avenues for future advancements in OOR.

A simply prepared amine oxide molecule as a low work function cathode modifier in organic photovoltaics for harvesting ambient light

Organic photovoltaics (OPV) that possibly convert ambient lights to electric energy are under the spotlight as a power supplier for portable, wearable, and Internet of Things devices. In order to enable the commercialization of ambient light harvesters, it is imperative to design and synthesize device components that offer cost-effectiveness, uniform deposition, and efficient charge extraction/collection. Here, we introduce a simple cathode interlayer (CIL) named EtNO for OPV-based ambient light harvesters. EtNO is designed with a chemical structure that does not require complicated conjugated units and is synthesized through a one-step procedure. EtNO CIL shows efficient reductions in the work function of electrodes, attributed to an interfacial dipole induced from an interaction between amine oxide group of EtNO and electrodes. Furthermore, EtNO forms a uniform layer through solution-processing without deteriorative effects on the surface of photoactive layer in OPVs. Therefore, the OPV with EtNO CIL exhibits an improved performance with an output power density of 79.2 μW cm–2 under light emitting diode illumination (1000 lx, 254 μW cm–2) compared to the device with conventional PDINO CIL (73.1 μW cm–2). Studies conducted on OPVs under halogen light illumination and on large-area devices further demonstrate the significant potential of EtNO as a CIL.

Green Oxidation of Amines Using Salicylic Acid Derivatives as Organocatalysts and Its Application to One-pot Synthesis of Pharmaceutical Molecules

Green Oxidation of Amines Using Salicylic Acid Derivatives as Organocatalysts and Its Application to One-pot Synthesis of Pharmaceutical Molecules

Positive Electronic Nickel Active Site Enhances N─H/C─H Bonds Breaking for Electrooxidation of Amines to Nitriles Coupling with Hydrogen Production

AbstractElectrocatalytic conversion of amines to nitriles can be used as biomass upgrading to assist hydrogen production in water electrolysis. However, achieving efficient N─H/C─H bond breaking in amines oxidation remains a challenge. Herein, the nitrogen‐doped carbon supported NiO nanoparticles with positive electronic nickel active site are simply synthesized to achieve ∽99% selectivity and complete conversion in electrooxidizing amines to nitriles, and the onset potential of the whole reaction is as low as 1.32 V vs. RHE. Detailed in situ characterizations and theoretical calculations prove that the carbon substrate enhances the interaction between the N 2p orbital of amines and the Ni 3d orbital, which favors the construction of an indirect oxidation intermediate state R‐CH2NH2···NiO(OH)abs and promotes the subsequent stepwise dehydrogenation to nitriles. This whole reaction produces 16.4 times more hydrogen than pure water splitting, facilitating the development of the chemicals industry and energy utilization.