Reduction Of Molecular Oxygen Research Articles

A cytochrome bd repressed by a MarR family regulator confers resistance to metals, nitric oxide, sulfide, and cyanide in Chromobacterium violaceum.

The terminal oxidases of bacterial respiratory chains rely on heme-copper (heme-copper oxidases) or heme (cytochrome bd ) to catalyze reduction of molecular oxygen to water. Chromobacterium violaceum is a facultative anaerobic bacterium that uses oxygen and other electron acceptors for respiration under conditions of varying oxygen availability. The C. violaceum genome encodes multiple respiratory terminal oxidases, but their role and regulation remain unexplored. Here, we demonstrate that CioAB, the single cytochrome bd from C. violaceum , protects this bacterium against multiple stressors that are inhibitors of heme-copper oxidases, including nitric oxide, sulfide, and cyanide. CioAB also confers C. violaceum resistance to iron, zinc, and hydrogen peroxide. This cytochrome bd is encoded by the cioRAB operon, which is under direct repression by the MarR-type regulator CioR. In addition, the cioRAB operon responds to quorum sensing and to cyanide, suggesting a protective mechanism of increasing CioAB in the setting of high endogenous cyanide production.

Enhanced Co-Adsorption of Alcohols and Amines for Visible Light Driven Oxidative Condensation Using Iron-Based MOF.

Imines are essential intermediates in organic transformations, and is generally produced by dehydrogenative condensation of alcohols and amines with the assist of specialized catalysts and additives. Heterogeneous photocatalysis provides a sustainable platform for such process without the using of toxic oxidants, yet a functionalized photocatalyst with optimized co-adsorption of reactants needs to be developed to promote the stoichiometric oxidative condensation under ambient conditions. Here, we show that benzyl alcohol and aniline adsorb non-interferingly on the Fe node and the linker sites of the MIL-53(Fe) metal organic frameworks (MOFs), respectively. The co-adsorption of both reactants barely influences the reduction of molecular oxygen to generate oxygen radicals, resulting in efficient formation of benzaldehyde under visible light. Additionally, the weak adsorption of water together with surface acidity of the MIL-53(Fe) promote a rapid condensation of benzaldehyde with aniline and the depletion of generated water, achieving an efficient C-N bond creation for a wide range of substrates.

Cryo-electron microscopy reveals hydrogen positions and water networks in photosystem II.

Photosystem II starts the photosynthetic electron transport chain that converts solar energy into chemical energy and thus sustains life on Earth. It catalyzes two chemical reactions: water oxidation to molecular oxygen and plastoquinone reduction. Coupling of electron and proton transfer is crucial for efficiency; however, the molecular basis of these processes remains speculative owing to uncertain water binding sites and the lack of experimentally determined hydrogen positions. We thus collected high-resolution cryo-electron microscopy data of fully hydrated photosystem II from the thermophilic cyanobacterium Thermosynechococcus vestitus to a final resolution of 1.71 angstroms. The structure reveals several previously undetected partially occupied water binding sites and more than half of the hydrogen and proton positions. This clarifies the pathways of substrate water binding and plastoquinone B protonation.

Interfacial and ion-pairing catalysis for oxygen-tolerant large-scale ATRP in ab initio emulsion

A cooperative interfacial and ion-pairing catalysis, coupled with a molecular oxygen reduction reaction (ORR), to scale up an Atom Transfer Radical Polymerization of n-butyl acrylate (BA) from 20 mL to 10 L (scale-up factor = 500) in ab initio emulsion conditions is introduced. The polymerization is driven by the regeneration of [CuIL]+ through CuII/Cu0 comproportionation. [CuIL]+ simultaneously converts O2 to H2O2 (which is then degraded by sodium pyruvate) and drives the polymerization of butyl acrylate. The anionic surfactant sodium dodecyl sulfate (SDS) facilitates catalyst transport inside and outside the micelles by ion-pairing catalysis. n-Butyl acrylate polymerizations are investigated on a small scale with Cu0 wire and on a larger scale with Cu0 powder. On a 10 L scale, the polymerization yielded controlled PBA-Br (Mn = 32.3 × 103; Ð = 1.39, ∼1.64 kg) after 9 h. Chain extension of PBA-Br macroinitiators proved their livingness. An on-line electrochemical monitoring was also introduced to determine the instantaneous CuI and CuII concentrations at the Cu0 wire surface during the polymerization.

Laccase is a multitasking protein for synthetic gene circuits in the yeast Saccharomycescerevisiae

Laccase is a multicopper oxidase enzyme that oxidizes a variety of substrates, including polyphenols and polycyclic aromatic hydrocarbons (PAHs). It catalyzes the four-electron reduction of molecular oxygen that results in the production of water as a by-product. Thus, laccase can play an important role in environmental care. Previously, we have successfully expressed Trametes trogii laccase (TtLcc1) in the yeast Saccharomyces cerevisiae. In this work, we have expressed in yeast another laccase, LacA from Trametes sp. AH28-2, and tested its function on PAHs. Yeast cells engineered to produce the two laccases performed efficient PAH degradation. Both TtLcc1 and LacA led to the construction of spatiotemporal fluorescence-pulse generators when combined with a benzoate/salicylate yeast biosensor in a two-population system. Moreover, laccases returned a visual output signal in yeast synthetic circuits—upon reacting with ABTS (2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)). Thus, in S. cerevisiae, laccases are a powerful alternative to fluorescent reporter proteins.

Extending the understanding of Shannon's safe stimulation limit for platinum electrodes: biphasic charge-balanced pulse trains in unbuffered saline at pH = 1 to pH = 12.

In neural electrical stimulation, safe stimulation guidelines are essential to deliver efficient treatment by avoiding neural damage and electrode degradation. The widely used Shannon's limit, k, gives conditions on the stimulation parameters to avoid neural damage, however, underlying damage mechanisms are not fully understood. Moreover, the translation from bench testing to in vivo experiments still presents some challenges, including the increased polarisation observed, which may influence charge-injection mechanisms. In this work, we studied the influence on damage mechanisms of two electrolyte parameters that are different in vivo compared to usual bench tests: solution pH and electrolyte gelation. The potential of a platinum macroelectrode was monitored in a three-electrode setup during current-controlled biphasic charge-balanced cathodic-first pulse trains. Maximum anodic and cathodic potential excursions during pulse trains were projected on cyclic voltammograms to infer possible electrochemical reactions. In unbuffered saline of pH ranging from 1 to 12, the maximum anodic potential was systematically located in the oxide formation region, while the cathodic potential was located the molecular oxygen and oxide reduction region when k approached Shannon's damage limit, independent of solution pH. The results support the hypothesis that Shannon's limit corresponds to the beginning of platinum dissolution following repeated cycles of platinum oxidation and reduction, for which the cathodic excursion is a key tipping point. Despite similar potential excursions between solution and gel electrolytes, we found a joint influence of pH and gelation on the cathodic potential alone, while we observed no effect on the anodic potential. We hypothesise that gelation creates a positive feedback loop exacerbating the effects of pH ; however, the extent of that influence needs to be examined further. This work supports the hypothesis of charge injection mechanisms associated with stimulation-induced damage at platinum electrodes. The validity of a major hypothesis explaining stimulation-induced damage was tested and supported on a range of electrolytes representing potential electrode environments, calling for further characterisation of platinum dissolution during electrical stimulation in various testing conditions.

Synthesis of Quinazolinones and Benzothiazoles Using α-Keto Acids under Ball Milling.

Mechanochemistry refers to the initiation of chemical reactions via mechanical forces such as milling, grinding, or shearing to achieve the chemical transformations. As a manifestation of mechanocatalysis, herein, an oxidant-free and solvent-free approach for the synthesis of quinazolinones (23 derivatives) and benzothiazoles (23 derivatives) has been developed through stainless-steel-driven decarboxylative acyl radical generation from α-keto acids. A library of 2-arylquinazolinones and 2-arylbenzothiazoles has been prepared in moderate to good yields at room temperature. Moreover, control experiments and XPS studies supported the reduction (by zerovalent iron) of molecular oxygen through the moderate abrasion of balls, which promoted the generation of a superoxide radical anion via a SET process.

Alternative Methods for the Detection of Superoxide Anion Generation in Platelets.

Reactive oxygen species (ROS) are highly unstable oxygen-containing molecules. Their chemical instability makes them extremely reactive and gives them the ability to react with important biological molecules such as proteins, nucleic acids, and lipids. Superoxide anions are important ROS generated by the reduction of molecular oxygen reduction (i.e., acquisition of one electron). Despite their initial implication exclusively in aging, degenerative, and pathogenic processes, their participation in important physiological responses has recently become apparent. In the vascular system, superoxide anions have been shown to modulate the differentiation and function of vascular smooth muscle cells, the proliferation and migration of vascular endothelial cells in angiogenesis, the immune response, and the activation of platelets in hemostasis. The role of superoxide anions is particularly important in the dysregulation of platelets and the cardiovascular complications associated with a plethora of conditions, including cancer, infection, inflammation, diabetes, and obesity. It has, therefore, become extremely relevant in cardiovascular research to be able to effectively measure the generation of superoxide anions byhuman platelets,understand the redox-dependent mechanisms regulating the balance between hemostasis and thrombosis and, eventually,identify novel pharmacological tools for the modulation of platelet responses leading to thrombosis and cardiovascular complications. This study presents three experimental protocols successfully adopted for the detection of superoxide anions in platelets and the study of the redox-dependent mechanisms regulating hemostasis and thrombosis: 1) dihydroethidium (DHE)-based superoxide anion detection by flow cytometry; 2) DHE-based superoxide anion visualization and analysis by single platelet imaging; and 3) spin probe-based quantification of superoxide anion output in platelets by electron paramagnetic resonance (EPR).

Reduction of molecular oxygen in flavodiiron proteins - Catalytic mechanism and comparison to heme-copper oxidases

The family of flavodiiron proteins (FDPs) plays an important role in the scavenging and detoxification of both molecular oxygen and nitric oxide. Using electrons from a flavin mononucleotide cofactor molecular oxygen is reduced to water and nitric oxide is reduced to nitrous oxide and water. While the mechanism for NO reduction in FDPs has been studied extensively, there is very little information available about O2 reduction. Here we use hybrid density functional theory (DFT) to study the mechanism for O2 reduction in FDPs. An important finding is that a proton coupled reduction is needed after the O2 molecule has bound to the diferrous diiron active site and before the OO bond can be cleaved. This is in contrast to the mechanism for NO reduction, where both NN bond formation and NO bond cleavage occurs from the same starting structure without any further reduction, according to both experimental and computational results. This computational result for the O2 reduction mechanism should be possible to evaluate experimentally. Another difference between the two substrates is that the actual OO bond cleavage barrier is low, and not involved in rate-limiting the reduction process, while the barrier connected with bond cleavage/formation in the NO reduction process is of similar height as the rate-limiting steps. We suggest that these results may be part of the explanation for the generally higher activity for O2 reduction as compared to NO reduction in most FDPs. Comparisons are also made to the O2 reduction reaction in the family of heme‑copper oxidases.

Identification of a Durability Descriptor for Molecular Oxygen Reduction Reaction Catalysts.

The development of durable platinum-group-metal-free oxygen reduction reaction (ORR) catalysts is a key research direction for enabling the wide use of fuel cells. Here, we use a combination of experimental measurements and density functional theory calculations to study the activity and durability of seven iron-based metallophthalocyanine (MPc) ORR catalysts that differ only in the identity of the substituent groups on the MPcs. While the MPcs show similar ORR activity, their durabilities as measured by the current decay half-life differ greatly. We find that the energy difference between the hydrogenated intermediate structure and the final demetalated structure (ΔEdemetalation) of the MPcs is linearly related to the degradation reaction barrier energy. Comparison to the degradation data for the previously studied metallocorrole systems suggested that ΔEdemetalation also serves as a descriptor for the corrole systems and that the high availability of protons at the active site due to the COOH group of the o-corrole decreases the durability.

Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10–SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha© (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein‐coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep.

Investigation of the Mechanism of Membrane Potential Generation by Heme-Copper Respiratory Oxidases in a Real Time Mode.

Heme-copper respiratory oxidases are highly efficient molecular machines. These membrane enzymes catalyze the final step of cellular respiration in eukaryotes and many prokaryotes: the transfer of electrons from cytochromes or quinols to molecular oxygen and oxygen reduction to water. The free energy released in this redox reaction is converted by heme-copper respiratory oxidases into the transmembrane gradient of the electrochemical potential of hydrogen ions H+). Heme-copper respiratory oxidases have a unique mechanism for generating H+, namely, a redox-coupled proton pump. A combination of direct electrometric method for measuring the kinetics of membrane potential generation with the methods of prestationary kinetics and site-directed mutagenesis in the studies of heme-copper oxidases allows to obtain a unique information on the translocation of protons inside the proteins in real time. The review summarizes the data of studies employing time-resolved electrometry to decipher the mechanisms of functioning of these important bioenergetic enzymes.

Structural insights into functional properties of the oxidized form of cytochrome c oxidase

Cytochrome c oxidase (CcO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the CcO reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable OH state, and a reductive phase, in which OH is reduced back to the R state. During each phase, two protons are translocated across the membrane. However, if OH is allowed to relax to the resting oxidized state (O), a redox equivalent to OH, its subsequent reduction to R is incapable of driving proton translocation. Here, with resonance Raman spectroscopy and serial femtosecond X-ray crystallography (SFX), we show that the heme a3 iron and CuB in the active site of the O state, like those in the OH state, are coordinated by a hydroxide ion and a water molecule, respectively. However, Y244, critical for the oxygen reduction chemistry, is in the neutral protonated form, which distinguishes O from OH, where Y244 is in the deprotonated tyrosinate form. These structural characteristics of O provide insights into the proton translocation mechanism of CcO.

Regulation Mechanism of Electron Transfer Reaction from Cytochrome C to Cytochrome C Oxidase

The respiratory chain in mitochondria is quite essential for the energy generation in cells, effectively producing “the energy currency in living organisms”, ATP. The driving force for this system is a series of electron transfers form Complex I (NADH:quinone oxidoreductase) to Complex IV (Cytochrome c Oxidase; CcO) in inner mitochondria membrane, and these electron transfer reactions promote the proton pumping from the matrix to the intermembrane space in mitochondria, and, by use of the resulting proton concentration gradient across the membrane, Complex V (ATP synthase) produces ATP. These series of electron transfer reactions terminate at CcO to reduce molecular oxygen to water molecules. The electrons required for this four-electron reduction of molecular oxygen in CcO are donated from a small soluble electron transfer hemoprotein, Cytochrome c (Cyt c), and this electron transfer is also associated with the proton pumping for the ATP generation in the respiratory chain. To examine the molecular regulation mechanism of the electron transfer reaction to terminate the electron transport chain for four-electron reduction of molecular oxygen and proton pumping for the ATP generation, we kinetically followed the electron transfer reaction and analyzed the electron transfer reaction by the Michaelis-Menten equation. By utilizing the Cyt c mutants, we identified the amino acid residues to regulate the electron transfer reactions (Biochem. J., 2020, 477,1565). The kinetic analysis of the electron transfer reaction also revealed that the apparent rate for the electron transfer reaction determined by the steady-state kinetics is much slower than the intramolecular electron transfer rate in the Cyt c – CcO complex. On the other hand, we successfully determined the interaction site between Cyt c and CcO by using NMR (Proc. Natl. Acad. Sci., 2011, 108, 12271) and protein-protein docking simulation (J. Biol. Chem., 2016, 291, 15320). The Cyt c – CcO complex structure estimated from the NMR and protein-protein docking simulation clearly showed that the two redox centers, heme iron in Cyt c and CuA in subunit II of CcO, were located more than 20 Å apart, and the complexes exhibiting shorter redox center distances were energetically unstable. Combined with the results from kinetic and structural studies, we proposed a “conformationally gated electron transfer mechanism”, where the thermal fluctuation of the protein structure controls the electron transfer rate. However, direct experimental evidence that protein conformational fluctuations regulate electron transfer reactions has not been obtained. In this study, we focused on the viscosity of the protein solution as a factor to regulate the conformational fluctuation of the proteins, based on the assumption that high viscosity of the solution suppresses the conformational fluctuation. The electron transfer reaction from Cyt c to CcO was examined in the high viscosity solution and NMR relaxation measurements under high viscosity were also performed to identify the local structural fluctuation responsible for the regulation of the electron transfer rate. Together with the transient complex structures between Cyt c and CcO estimated by the MD simulation, the regulation mechanism of the electron transfer from Cyt c to CcO based on the “conformational gating” will be discussed.

One-Pot Graphene Supported Pt3Cu Nanoparticles—From Theory towards an Effective Molecular Oxygen Reduction Reaction Catalyst

In this work, recent research progresses in the formation of Pt3Cu nanoparticles onto the surface of graphene are described, and the obtained results are contrasted with previously published theoretical studies. To form these nanoparticles, tetrabutylammonium hexachloroplatinate, and copper acetylacetonate are used as platinum and copper precursors, respectively. Oleylamine is used as a reductor and a solvent. The obtained catalyst is characterized via X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy dispersive spectroscopy X-ray (EDS). To assess the catalytic activity, the graphene-supported Pt3Cu material is tested with cyclic voltammetry, “CO stripping”, and oxygen reduction reaction potentiodynamic curves to find the nature and the intrinsic electrochemical activity of the material. It can be observed that the tetrabutylammonium cation plays a critical role in anchoring and supporting nanoparticles over graphene, from which a broad discussion about the true nature of the anchoring mechanism was derived. The growth mechanism of the nanoparticles on the surface of graphene was observed, supporting the conducted theoretical models. With this study, a reliable, versatile, and efficient synthesis of nanocatalysts is presented, demonstrating the potentiality of Pt3Cu/graphene as an effective cathode catalyst. This study demonstrates the importance of reliable ab inito theoretical results as a useful source of information for the synthesis of the Pt3Cu alloy system.

Heterogeneous Photocatalytic Recycling of FeX2/FeX3 for Efficient Halogenation of C-H Bonds Using NaX.

Environmental-friendly halogenation of C-H bonds using abundant, non-toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X = Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3. Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications.

Heterogeneous Photocatalytic Recycling of FeX2/FeX3 for Efficient Halogenation of C−H Bonds Using NaX

AbstractEnvironmental‐friendly halogenation of C−H bonds using abundant, non‐toxic halogen salts is in high demand in various chemical industries, yet the efficiency and selectivity of laboratory available protocols are far behind the conventional photolytic halogenation process which uses hazardous halogen sources. Here we report an FeX2 (X=Br, Cl) coupled semiconductor system for efficient, selective, and continuous photocatalytic halogenation using NaX as halogen source under mild conditions. Herein, FeX2 catalyzes the reduction of molecular oxygen and the consumption of generated oxygen radicals, thus boosting the generation of halogen radicals and elemental halogen for direct halogenation and indirect halogenation via the formation of FeX3. Recycling of FeX2 and FeX3 during the photocatalytic process enables the halogenation of a wide range of hydrocarbons in a continuous flow, rendering it a promising method for applications.

Carbon spheres modified titanium air diffusion cathode for boosting H2O2 and application in disinfection

In situ electrochemical disinfection via H2O2 through two-electron molecular oxygen reduction reaction (2e-ORR) represents a promising strategy for sustainable disinfection. However, its disinfection performance is largely confined by its low selectivity/reactivity towards two-electron oxygen reduction reaction (2e-ORR) for H2O2 production. To tackle this, carbon spheres modified tubular titanium air diffusion cathode (CS@TTC) was developed. It intended to improve interfacial structures for high H2O2 production through a facile hydrothermal carbonation approach. Evolution of morphology and chemical nature of carbon spheres have been systemically investigated under diverse hydrothermal temperature, hydrothermal time and pyrolysis temperature·H2O2 accumulation has improved 6.59-fold at CS@TTC compared to the raw base TTC. Both chemical nature of carbon sphere and a superior oxygen mass transfer (0.0284 s−1) were responsible for this enhancement. Besides, CS@TTC cathode was used in the electrochemical system for disinfection performance, in which 6.42 log of E. coli was deactivated after 120 min. Hence, this study gives an insight into that the H2O2-based electrochemical disinfection is promising to be a next-generation process.

Role of oxidative stress in Alzheimer's disease

Alzheimer's disease is the leading cause of disability in people over 65. Amyloid (Aβ) peptide deposition, neurofibrillary tangles of hyperphosphorylated protein, and dementia are hallmarks of AD [1]. The neurotoxic oligomer Aβ peptide and tau protein [2] mediate neurodegeneration, one of the main causes of the disease. Oxidative stress [3], an imbalance between antioxidants and oxidants, causes and exacerbates these symptoms. Free radicals, which have one or more unpaired electrons in their outer shell, can augment or reduce antioxidant defence, causing this imbalance. The reduction of molecular oxygen in water produces superoxide, which produces hydrogen peroxide by adding an electron. Reactive oxygen species (ROS) [4]—hydroxyl radicals produced by hydrogen peroxide reduction—can react with lipids, proteins, nucleic acids, and other molecules and change their structures and activities. Due to its makeup, ROS affects tissues and organs, particularly the sensitive brain. High oxygen usage and highly oxidizable lipids make up the brain.

Synergistic Catalytic Effects of CeCuO3 @ Vulcan Carbon Composites on the Oxygen Reduction Reaction

AbstractThe reduction of molecular oxygen is considered to be a key reaction for electrochemical energy conversion in direct methanol fuel cells (DMFCs). The slow kinetics of oxygen reduction reaction along with the high cost of Pt catalyst hampers the application of fuel cells. In this study, we have reported for the first time oxygen reduction reaction (ORR) activity on rare earth cerium containing perovskite oxides composite with vulcan carbon (VC) in alkaline media. The study has demonstrated the synergistic role of vulcan carbon in cerium perovskite nanomaterials‐VC composite for improving ORR activity. The 60 % CeCuO3‐VC perovskite oxide composite with surface areas of 180 m2/g showed better oxygen reduction capability as compared to that of bare cerium perovskite. On optimization, among all the prepared catalysts 60 % CeCuO3‐VC showed the highest ORR activity with low onset potential and high current density. Further, the optimized 60 % CeCuO3‐VC followed the 4e− pathway with 95 % methanol tolerance properties and high stability i.e 76 %. This study on cerium‐based perovskite with vulcan carbon will provide an opportunity for the study of rare earth cerium perovskite electrocatalysts for electrochemical energy conversion.