Oxidative Coupling Research Articles

Efficient Photocatalytic Oxidative Coupling of Amines under Visible Light Using a Trioporphyrins-Based Covalent Triazine Framework.

Porphyrins-based porous organic polymers (POP) were widely used in photocatalytic oxidation under visible light owing to their superiority in the activation of oxygen. In contrast, the efficiency is usually limited due to the fast recombination and slow electron transfer. Herein, we report the use of a trioporphyrins-based covalent triazine framework (Por-CTF) as visible-light-active photocatalyst for the coupling oxidative of amines to imines at room temperature. By incorporating the π-conjugated porphyrin building block led to the enhanced electron transport between molecules, and the extended recombination time of excited electrons. The photocatalytic efficiency of Por-CTF is superior to that of polymer in absence of triazine framework (POP-TSP), which was prepared by radical polymerization using tetra-(4-vinylphenyl) porphyrin (TSP) as monomer. Por-CTF catalyst presented excellent efficiency for various primary amines and stability. This work provides a reasonable guidance of catalyst molecular structure design for enhancing efficiency in the photocatalytic oxidation.

Two-Dimensional Covalent Organic Frameworks with Carbazole-Embedded Frameworks Facilitate Photocatalytic and Electrocatalytic Processes

Catalytic technologies are pivotal in enhancing energy efficiency, promoting clean energy production, and reducing energy consumption in the chemical industry. The pursuit of novel catalysts for renewable energy is a long-term goal for researchers. In this work, we synthesized three two-dimensional covalent organic frameworks (COFs) featuring electron-rich carbazole-based architectures and evaluated their catalytic performance in photocatalytic organic reactions and electrocatalytic oxygen reduction reactions (ORRs). Pyrene-functionalized COF, termed as FCTD-TAPy, demonstrated excellent photocatalytic performance for amino oxidation coupling and showed a remarkable preference for substrates with electron-withdrawing groups (up to >99% Conv. and >99% Sel). Furthermore, FCTD-TAPy favored a four-electron transfer pathway during the ORR and exhibited favorable reaction kinetics (51.07 mV/dec) and a high turnover frequency (0.011 s−1). In contrast, the ORR of benzothiadiazole-based FCTD-TABT favored a two-electron transfer pathway, which exhibited a maximum double-layer capacitance of 14.26 mF cm−2, a Tafel slope of 53.01 mV/dec, and a hydrogen peroxide generation rate of 70.3 mmol g−1 h−1. This work underscores the potential of carbazole-based COFs as advanced catalytic materials and offers new insights into the design of metal-free COFs for enhanced catalytic performance.

Cu‐Catalyzed Oxidative Tandem Coupling and Cyclization of 2‐Aminonaphthalenes to Synthesize Dibenzo[c, g]carbazoles

A Cu(II) complex with a bipyridyl ligand bearing a Brønsted acid was used to catalyze the tandem oxidative coupling and cyclization of 2‐aminonaphthalenes to give N‐substituted‐dibenzo[c,g]carbazoles. The incorporation of an appended acidic moiety to the ligand was found to be key to the selective formation of dibenzocarbazoles over 2,2’‐diamino‐1,1’‐binaphthalene (BINAM), which is known as an irreversible byproduct. This highly efficient method yields a wide array of dibenzo[c,g]carbazoles featuring diverse functional groups as well as electronic properties. The selected dibenzo[c,g]carbazoles exhibited high photoluminescence quantum yields of up to 100% and are promising chromophores for advanced materials.

Precise Single‐Atom Modification of Hybrid Lead Chlorides for Electron Donor‐Acceptor Effect and Enhanced Photocatalytic Aerobic Oxidation

Hybrid lead halides show significant potential in photocatalysis due to their excellent photophysical properties, but the atomically precise modification of their organic component to achieve synergistic interactions with the lead halide units remains a great challenge. Herein, for the first time, we have employed the crystal engineering strategy to construct a class of single‐atom‐substituted hybrid lead halides with electron donor‐acceptor (D‐A) effect. The lead halide frameworks consist of 1D linear [PbCl]+ chains as inorganic building units and benzoxadiazole/benzothiadiazole/ benzoselenadiazole‐funtionalized dicarboxylates as linkers. The covalent bonding between the organic ligands with electron‐withdrawing groups and the electron‐rich lead halide units not only facilitate the charge separation, but also enhance structural robustness that is critical for photocatalysis. The D‐A structured lead halides serve as highly efficient heterogeneous photooxidation catalysts, including aerobic oxidation of C(sp3)‐H bonds, oxidative coupling of primary amines, oxidation of phenylboronic acids and selective oxidation of sulfides that are demonstrated in 30 examples. Importantly, these photooxidation reactions are able to be driven by natural sunlight and ambient air to afford quantitative yields. Moreover, our lead halide photocatalysts are successful to fix into a photocatalytic flow system, which enables the flow‐type synthesis of high value‐added photooxidation products on a gram scale.

Precise Single-Atom Modification of Hybrid Lead Chlorides for Electron Donor-Acceptor Effect and Enhanced Photocatalytic Aerobic Oxidation.

Hybrid lead halides show significant potential in photocatalysis due to their excellent photophysical properties, but the atomically precise modification of their organic component to achieve synergistic interactions with the lead halide units remains a great challenge. Herein, for the first time, we have employed the crystal engineering strategy to construct a class of single-atom-substituted hybrid lead halides with electron donor-acceptor (D-A) effect. The lead halide frameworks consist of 1D linear [PbCl]+ chains as inorganic building units and benzoxadiazole/benzothiadiazole/ benzoselenadiazole-funtionalized dicarboxylates as linkers. The covalent bonding between the organic ligands with electron-withdrawing groups and the electron-rich lead halide units not only facilitate the charge separation, but also enhance structural robustness that is critical for photocatalysis. The D-A structured lead halides serve as highly efficient heterogeneous photooxidation catalysts, including aerobic oxidation of C(sp3)-H bonds, oxidative coupling of primary amines, oxidation of phenylboronic acids and selective oxidation of sulfides that are demonstrated in 30 examples. Importantly, these photooxidation reactions are able to be driven by natural sunlight and ambient air to afford quantitative yields. Moreover, our lead halide photocatalysts are successful to fix into a photocatalytic flow system, which enables the flow-type synthesis of high value-added photooxidation products on a gram scale.

Plasmid-free production of the plant lignan pinoresinol in growing Escherichia coli cells

BackgroundThe high-value aryl tetralin lignan (+)-pinoresinol is the main precursor of many plant lignans including (-)-podophyllotoxin, which is used for the synthesis of chemotherapeutics. As (-)-podophyllotoxin is traditionally isolated from endangered and therefore limited natural sources, there is a particular need for biotechnological production. Recently, we developed a reconstituted biosynthetic pathway from (+)-pinoresinol to (-)-deoxypodophyllotoxin, the direct precursor of (-)-podophyllotoxin, in the recombinant host Escherichia coli. However, the use of the expensive substrate (+)-pinoresinol limits its application from the economic viewpoint. In addition, the simultaneous expression of multiple heterologous genes from different plasmids for a multi-enzyme cascade can be challenging and limits large-scale use.ResultsIn this study, recombinant plasmid-free E. coli strains for the multi-step synthesis of pinoresinol from ferulic acid were constructed. To this end, a simple and versatile plasmid toolbox for CRISPR/Cas9-assisted chromosomal integration has been developed, which allows the easy transfer of genes from the pET vector series into the E. coli chromosome. Two versions of the developed toolbox enable the efficient integration of either one or two genes into intergenic high expression loci in both E. coli K-12 and B strains. After evaluation of this toolbox using the fluorescent reporter mCherry, genes from Petroselinum crispum and Zea mays for the synthesis of the monolignol coniferyl alcohol were integrated into different E. coli strains. The product titers achieved with plasmid-free E. coli W3110(T7) were comparable to those of the plasmid-based expression system. For the subsequent oxidative coupling of coniferyl alcohol to pinoresinol, a laccase from Corynebacterium glutamicum was selected. Testing of different culture media as well as optimization of gene copy number and copper availability for laccase activity resulted in the synthesis of 100 mg/L pinoresinol using growing E. coli cells.ConclusionsFor efficient and simple transfer of genes from pET vectors into the E. coli chromosome, an easy-to-handle molecular toolbox was developed and successfully tested on several E. coli strains. By combining heterologous and endogenous enzymes of the host, a plasmid-free recombinant E. coli growing cell system has been established that enables the synthesis of the key lignan pinoresinol.

Multifunctional nanomaterials composed entirely of active pharmaceutical ingredients for synergistically enhanced antitumor and antibacterial effects

IntroductionMultifunctional nanomaterials are emerging as promising tools for treating both cancer and bacterial infections. However, integrating dual therapeutic capabilities into a single system remains challenging. This study presents multifunctional nanoparticles (ECI-NPs) based on Epigallocatechin gallate (EGCG) oligomers, Curcumin (CUR), and Indocyanine Green (ICG) for combined cancer and bacterial treatment.MethodsECI-NPs were synthesized via oxidative coupling of EGCG, CUR, and ICG. The nanoparticles were characterized for stability, size, drug loading, and release profiles. Cellular uptake, phototoxicity in melanoma cells, and antibacterial activity against Escherichia coli and Staphylococcus aureus were also evaluated.ResultsECI-NPs demonstrated optimal stability, high drug loading, and controlled release. Cellular studies showed increased uptake and greater phototoxicity in melanoma cells compared to free drugs. ECI-NPs also exhibited enhanced anticancer effects and strong antibacterial activity, outperforming the individual components.DiscussionThe polyphenol-based ECI-NPs offer synergistic therapeutic effects, overcoming the limitations of free drugs in terms of solubility and efficacy. This dual-function platform shows potential for broader biomedical applications, addressing challenges in cancer and bacterial infections. Further research will focus on in vivo studies and clinical translation.

Covalent Pectin/Arabinoxylan Hydrogels: Rheological and Microstructural Characterization.

This research aimed to evaluate the gelation process of ferulated pectin (FP) and ferulated arabinoxylan (AXF) in a new mixed hydrogel and determine its microstructural characteristics. FP from sugar beet (Beta vulgaris) and arabinoxylan from maize (Zea mays) bran were gelled via oxidative coupling using laccase as a crosslinking agent. The dynamic oscillatory rheology of the mixed hydrogel revealed a maximum storage modulus of 768 Pa after 60 min. The scanning electron microscopy images showed that mixed hydrogels possess a microstructure of imperfect honeycomb. The ferulic acid content of the mixed hydrogel was 3.73 mg/g, and ferulic acid dimer 8-5' was the most abundant. The presence of a trimer was also detected. This study reports the distribution and concentration of ferulic acid dimers, and the rheological and microstructural properties of a mixed hydrogel based on FP and AXF, which has promising features as a new covalent biopolymeric material.

Enantioselective Electrocatalysis for the Cross-Dehydrogenative Heteroarylation of Indoles, Pyrroles, and Furans.

Oxidative cross-dehydrogenative C-H/C-H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α-heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2-acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene-assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni-bound α-carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero-compounds. The consequential α-heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (-)-COX-2 inhibitor, (+)-acremoauxin A, and (+)-pemedolac.

Intrinsic reactivity of stoichiometric IrO2(1 1 0) surface toward oxidative coupling of methane

This study investigates the oxidative coupling of methane on the IrO2(110) surface using TPRS simulations informed by DFT-derived data. We discover that the efficiency of the IrO2(110) surface in generating ethylene is strongly influenced by methane surface coverage. Our simulations reveal that the presence of surface hydroxyl group enhances the yield of C2+ species from methane oxidation, but this effect is counteracted at high methane coverages due to the accelerated formation of CH2OH. In addition, the study reveals that slight modifications in energy barriers at the branching point (C2H4 formation vs. CH2OH formation) significantly affect C2H4(g) production from the simulation, underscoring the importance of precise energetic data for accurate catalytic reaction predictions. The results have broader implications for reactions and catalysts where branching point selectivity determines high-value product yields. Thus, combining surface science with computational analysis is crucial for accurately determining energy profiles of key steps at the branching points.

Enantioselective Electrocatalysis for the Cross‐Dehydrogenative Heteroarylation of Indoles, Pyrroles, and Furans

Oxidative cross‐dehydrogenative C‐H/C‐H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α‐heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2‐acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene‐assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni‐bound α‐carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero‐compounds. The consequential α‐heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (‐)‐COX‐2 inhibitor, (+)‐acremoauxin A, and (+)‐pemedolac.

Investigation of Electrocatalytic Oxidative Coupling of Arylamines for the Selective Synthesis of Azo Aromatics.

An electrochemical oxidative coupling of anilines to selectively provide azo aromatic compounds by using mild reaction conditions has been investigated. Further, the generality and feasibility of the developed protocol were showcased by synthesizing differently substituted azo compounds in moderate to good isolated yields. Additionally, different control experiments were performed to investigate the reaction mechanism. These experiments indicated the formation of hydrazobenzene as an intermediate while ruling out the possibility of nitrobenzene or nitroso-benzene formation during this transformation.

Dinickel-Catalyzed N=N Coupling Reactions for the Synthesis of Hindered Azoarenes.

Azoarenes are the largest class of photoswitching molecules, and they have a broad range of applications in photopharmacology and materials science. Azoarenes possessing ortho-substitution often display improved properties, including isomerization under visible light irradiation, near-quantitative switching, and long thermal half-lives in the cis form. The synthesis of hindered ortho-substituted azoarenes is often low-yielding using established oxidative or reductive coupling methods. Here, we describe the design and synthesis of a new dinickel complex that catalyzes the dimerization of ortho-substituted aryl azides in high yield. Applications of this method in the synthesis of high-performance photoswitches, photoactive peptide cross-linkers, hindered diazocines, and main-chain azoarene polymers are described.

Regioselective Oxidative Phenol Coupling by a Mushroom Unspecific Peroxygenase.

Bioactive dimeric (pre-)anthraquinones are ubiquitous in nature and are found in bacteria, fungi, insects, and plants. Their biosynthesis via oxidative phenol coupling (OPC) is catalyzed by cytochrome P450 enzymes, peroxidases, or laccases. While the biocatalysis of OPC in molds (Ascomycota) is well-known, the respective enzymes in mushroom-forming fungi (Basidiomycota) are unknown. Here, we report on the biosynthesis of the atropisomers phlegmacin A1 and B1 of the mushroom Cortinarius odorifer. The biosynthesis of these unsymmetrically 7,10'-homo-coupled dihydroanthracenones was heterologously reconstituted in the mold Aspergillus niger. Methylation of the parental monomer atrochrysone to its 6-O-methyl ether torosachrysone by the O-methyltransferase CoOMT1 precedes the regioselective homocoupling to phlegmacin, catalyzed by the enzyme CoUPO1 annotated as an "unspecific peroxygenase" (UPO). Our results reveal an unprecedented UPO reaction, thereby expanding the biocatalytic portfolio of oxidative phenol coupling beyond the commonly reported enzymes. The results show that Basidiomycota use peroxygenases to selectively couple aryls independently of and convergently to any other group of organisms, emphasizing the central role of OPC in natural processes.

Organoiodine Catalysed Intramolecular C−N bond Oxidative Coupling for the Synthesis of 3‐Monosubstituted Oxindoles

An efficient organoiodine‐catalysed intramolecular direct C–N bond oxidative coupling reaction is presented. Structurally diverse 3‐(mono)substituted oxindoles were rapidly obtained in a complex oxidative system in up to 87% yield. Various N‐alkoxy‐2‐phenylpropanamides were well‐tolerated. This study showed that the electronic effects on the aromatic ring of reactants have a crucial effect on the selectivity (C−N/C−O) of cyclisation products. In addition, gram‐scale synthesis and late‐stage modification of 3‐(mono)substituted oxindole derivatives revealed the practical application of this transformation.

Biopharmaceutical modulatory effects of newly engineered bile acid-Tyloxapol nanogels for attenuation of cytotoxicity in auditory cells

This study presents novel thermoresponsive nanogels composed of chenodeoxycholic acid and Tyloxapol for potential inner ear drug delivery. The nanogels exhibit non-Newtonian, shear-thinning fluid behaviour and rapid gelation at body temperature. Biocompatibility studies were conducted on auditory and macrophage cell lines. Nanogels had a minimal impact on cellular viability, glycolysis, and mitochondrial respiration of auditory cells after 24 h of exposure. However, mitochondrial function analysis in macrophages revealed a significant decrease in oxidative phosphorylation and coupling efficiency after nanogel exposure, accompanied by increased proton leakage. Despite these metabolic disruptions, glycolysis remained unaffected. The Poloxamer matrix appears to be responsible for these effects, independent of the presence of bile acids or Tyloxapol. This study highlights the potential of bile acid-enriched nanogels in drug delivery, particularly their biocompatibility and injectability while acknowledging challenges related to mitochondrial dysfunction in immune cells. These findings suggest that thermoresponsive bile acid and Tyloxapol nanogels have the potential to be safe and effective drug delivery vehicles for inner ear applications.

Construction of Donor-Acceptor-Type Conjugated Microporous Polymers by Oxidative Coupling of Boranil-Carbazole Mixed Monomers for Enhanced Photocatalytic Oxidation.

Conjugated microporous polymers (CMPs), featuring photoactive structures, a high surface area, robust thermal stability, and facile modulation, provide a versatile platform for fabricating diverse heterogeneous photocatalysts. The incorporation of donor-acceptor (D-A) structures into CMPs to increase their charge separation potential and enhance the photocatalytic efficacy is a viable strategy. In this work, we designed and synthesized a unique set of D-A monomers, incorporating boranil dyes as electron-deficient moieties and carbazoles as electron-rich subunits. Subsequently, D-A CMPs were prepared via an economical and environmentally friendly oxidation coupling reaction, and their potential in photocatalytic oxidation reactions was investigated. Modulation of the polymer's photoelectronic properties and photocatalytic performance can be achieved by adjusting the boranil content in the monomer. The polymer pCZFB-3, with the highest content of boranil units, exhibited an optimal photocatalytic activity. This finding confirms that strengthening the D-A effect can significantly enhance a catalyst's photoelectronic properties and catalytic efficacy. This study presents insights into designing innovative heterogeneous photocatalysts based on boron-containing dyes.

Reaction ignition during the oxidative coupling of methane over Mn–Na2WO4/SiO2

The present study investigates the oxidative coupling of methane (OCM) as a viable solution for CH4 upgrading with the benchmark Mn–Na2WO4/SiO2 catalyst. The effects of space velocity on catalytic performance and ignition responses were evaluated. Experimental catalytic tests revealed a complex relationship between space velocity and C2+ product yields and a self-igniting behavior when the reaction temperature reached about 700 °C. The results indicated that the temperature difference (∆T) between the catalyst bed and the flowing gas increased with the feed flow rate and decreased with dilution of the catalyst bed (increasing with catalyst loading), which can allow the reaction ignition at lower temperatures. The present study sheds light on the interplay between reaction conditions and the ignition behavior, providing valuable insights for optimization of OCM processes and catalyst development.

Rhodium Catalysts Based on Phenyl Substituted Cp Ligands for Indole Synthesis via Oxidative Coupling of Acetanilides and Alkynes

AbstractRhodium‐catalyzed oxidative coupling of acetanilides and alkynes via C−H activation is the most powerful synthetic tool for producing the indole motif from commercially available precursors. However, this reaction usually requires large catalyst loadings (5 mol% of rhodium). In this study, a 1,2‐diphenylcyclopentadienyl ligand‐based catalyst was developed that works well at 1 mol% loading of rhodium. DFT calculations of the C−H activation step provided insight into its high catalytic activity. The catalyst efficiency was also demonstrated in the synthesis of naturally occurring isocoumarins, such as polygonolide, tubakialactone B and penicimarine F. The developed catalytic protocols tolerate a wide range of functional groups, for example, halide, nitro, hydroxy, and alkoxy.

One-pot synthesis of carbon dots/hydrochar and visible-light-driven photocatalysts for aerobic oxidative coupling of benzylic amines

Utilizing selective photocatalysis conversion of amines represents an environmentally sustainable and economically feasible approach to generating valuable chemical products in the industry. Herein, carbon dots (CDs) incorporated in hydrochar (CDs/HCPP) were synthesized by one-pot hydrothermal carbonization of pomelo peel (PP) coupled with freeze-drying and used for aerobic oxidative coupling of benzylic amines. CDs were produced using only the pomelo peel as the carbon source, without the addition of any extra carbon additives. CDs/HCPP exhibited the greatest catalytic activity, achieving a benzylamine conversion rate of 99%, which was nearly 5.5 times of carbonized PP (CPP) without CDs and 1.14 times of CDs alone. Additionally, the oxidation of other amines, such as p -substituted benzylamines with groups that donate and withdraw electrons, was also demonstrated to be highly active and reusable using CDs/HCPP. This study has the potential to pave the way for novel methodologies and insights into synthesizing biomass composites adorned with CDs, enhancing the efficacy of photocatalytic syntheses.