Fenton-like Chemistry by a Copper(I) Complex and H<sub>2</sub>O<sub>2</sub> Relevant to Enzyme Peroxygenase C–H Hydroxylation

Kim, Bohee; Brueggemeyer, Magdalene T.; Transue, Wesley J.; Park, Younwoo; Cho, Jaeheung; Siegler, Maxime A.; Solomon, Edward I.; Karlin, Kenneth D.

doi:10.1021/jacs.3c02273

Cited by 24 publications

(12 citation statements)

References 91 publications

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“…In the subsequent phase, Cu(I) can activate H 2 O 2 via a Fenton-type mechanism, ,,, leading to the homolytic O–O cleavage and the formation of OH • radical. This type of reaction has been proved to be favorable in LPMOs. − Figure S20 shows the calculated energy profile.…”

Section: Resultsmentioning

confidence: 99%

“…Intriguingly, our simulations unexpectedly unveiled that evolutionarily conserved Glu228 extends into the coordination sphere of the Cu C site, a phenomenon not observed across the cryo-EM structures. Due to the coordination of Glu228 to Cu C , the cavity between Cu C and Cu D can be remarkably compressed (Figures 6 and S13c), which imparts a considerable constraint, rendering the In the subsequent phase, Cu(I) can activate H 2 O 2 via a Fenton-type mechanism, 37,73,75,76 leading to the homolytic O− O cleavage and the formation of OH • radical. This type of reaction has been proved to be favorable in LPMOs.…”

Section: Can Both Cu C and Cu D Sites Be Simultaneously Occupied By C...mentioning

confidence: 99%

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Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

Peng,

Wang,

Zhang

et al. 2023

J. Am. Chem. Soc.

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Particulate methane monooxygenase (pMMO) plays a critical role in catalyzing the conversion of methane to methanol, constituting the initial step in the C1 metabolic pathway within methanotrophic bacteria. However, the membrane-bound pMMO’s structure and catalytic mechanism, notably the copper’s valence state and genuine active site for methane oxidation, have remained elusive. Based on the recently characterized structure of membrane-bound pMMO, extensive computational studies were conducted to address these long-standing issues. A comprehensive analysis comparing the quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulated structures with cryo-EM data indicates that both the CuC and CuD sites tend to stay in the Cu(I) valence state within the membrane environment. Additionally, the concurrent presence of Cu(I) at both CuC and CuD sites leads to the significant reduction of the ligand-binding cavity situated between them, making it less likely to accommodate a reductant molecule such as durohydroquinone (DQH2). Subsequent QM/MM calculations reveal that the CuD(I) site is more reactive than the CuC(I) site in oxygen activation, en route to H2O2 formation and the generation of Cu(II)–O•– species. Finally, our simulations demonstrate that the natural reductant ubiquinol (CoQH2) assumes a productive binding conformation at the CuD(I) site but not at the CuC(I) site. This provides evidence that the true active site of membrane-bound pMMOs may be CuD rather than CuC. These findings clarify pMMO’s catalytic mechanism and emphasize the membrane environment’s pivotal role in modulating the coordination structure and the activity of copper centers within pMMO.

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Section: Resultsmentioning

confidence: 99%

Section: Can Both Cu C and Cu D Sites Be Simultaneously Occupied By C...mentioning

confidence: 99%

Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

Peng,

Wang,

Zhang

et al. 2023

J. Am. Chem. Soc.

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“…These hydroxyl radicals are prone to induce oxidative modifications of ligands, as recently reported. [58] Consequently, understanding the inactivation pathways and optimizing the stability of the catalysts would be interesting prospects for future investigations. Notably, it has been shown that LPMO undergoes autooxidative and inactivation events, possibly releasing free copper as well.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

LPMO‐like Activity of Bioinspired Copper Complexes: From Model Substrate to Extended Polysaccharides

Leblay,

Delgadillo‐Ruíz,

Decroos

et al. 2023

ChemCatChem

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Polysaccharide oxidative depolymerization is highly desirable to achieve recalcitrant biomass valorization. Inspired by recently discovered Lytic Polysaccharide Monooxygenases, mononuclear copper complexes have been prepared and studied in the literature. However, the activities were evaluated on different substrates and under various conditions. In this work we intended to establish a robust and reproducible activity assay, in aqueous solution at a pH close from neutrality and under mild conditions. We have evaluated several complexes on substrates of increasing complexity: the model substrate para‐nitrophenyl‐β‐D‐glucopyranoside (p‐NPG), cellobiose (glucose dimer), as well as on extended substrates (chitin, cellulose and bagasse from agave). The different assays were compared and proof‐of‐concept that bioinspired complexes can oxidatively promote polysaccharide depolymerization was obtained. Finally, we measured level of hydroxyl radicals released by the complexes under comparable experimental conditions and mechanistic pathways are discussed.

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“…Further addition of a e − /H + yields a copper(II)− hydroxo species which may act (i) as a substrate oxidant/ proton acceptor or (ii) via rebound, Cu II OH + R • → Cu I + ROH. 11 Elucidation of the (bio)chemistry of copper−oxygen fragments and their transformations or interconversions is the goal of multiple research communities. How are Cu II (O 2…”

Section: Introductionmentioning

confidence: 99%

“…A Cu II –oxyl is a copper-ligated deprotonated hydroxyl radical Cu II –O • formed via peroxide O–O bond cleavage and reduction–protonation (Figure ). Further addition of a e – /H + yields a copper(II)–hydroxo species which may act (i) as a substrate oxidant/proton acceptor or (ii) via rebound, Cu II OH + R • → Cu I + ROH . Elucidation of the (bio)chemistry of copper–oxygen fragments and their transformations or interconversions is the goal of multiple research communities.…”

Section: Introductionmentioning

confidence: 99%

Ligand–Copper(I) Primary O₂-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides

Kim,

Karlin

2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: In this Account, we overview and highlight synthetic bioinorganic chemistry focused on initial adducts formed from the reaction of reduced ligand−copper(I) coordination complexes with molecular oxygen, reactions that produce ligand− Cu II (O 2•−) complexes (O 2 •− ≡ superoxide anion). We provide mostly a historical perspective, starting in the Karlin research group in the 1980s, emphasizing the ligand design and ligand effects, structure, and spectroscopy of these O 2 adducts and subsequent further reactivity with substrates, including the interaction with a second ligand−Cu I complex to form binuclear species. The Account emphasizes the approach, evolution, and results obtained in the Karlin group, a synthetic bioinorganic research program inspired by the state of knowledge and insights obtained on enzymes possessing copper ion active sites which process molecular oxygen. These constitute an important biochemistry for all levels/types of organisms, bacteria, fungi, insects, and mammals, including humans.Copper is earth abundant, and its redox properties in complexes allow for facile Cu II /Cu I interconversions. Simple salts or coordination complexes have been well known to serve as oxidants for the stoichiometric or catalytic oxidation or oxygenation (i.e., O-atom insertion) of organic substrates. Thus, copper dioxygen-or peroxide-centered synthetic bioinorganic studies provide strong relevance and potential application to synthesis or even the development of cathodic catalysts for dioxygen reduction to hydrogen peroxide or water, as in fuel cells. The Karlin group's focus however was primarily oriented toward bioinorganic chemistry with the goal to provide fundamental insights into the nature of copper−dioxygen adducts and further reduced and/or protonated derivatives, species likely occurring in enzyme turnover or related in one or more aspects of formation, structure, spectroscopic properties, and scope of reactivity toward organic/biochemical substrates. Prior to this time, the 1980s, O 2 adducts of redox-active first-row transition-metal ions focused on iron, such as the porphyrinate−Fe centers occurring in the oxygen carrier proteins myoglobin and hemoglobin and that determined to occur in cytochrome P-450 monooxygenase turnover. Deoxy (i.e., reduced Fe(II)) heme proteins react with O 2 , giving Fe III −superoxo complexes (preferably referred to by traditional biochemists as ferrous−oxy species). And, it was in the 1970s that great strides were made by synthetic chemists in generating hemes capable of forming O 2 adducts, their physiochemical characterization providing critical insights to enzyme (bio)chemistry and providing ideas and important goals leading to countless person years of future research.

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Fenton-like Chemistry by a Copper(I) Complex and H₂O₂ Relevant to Enzyme Peroxygenase C–H Hydroxylation

Cited by 24 publications

References 91 publications

Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

LPMO‐like Activity of Bioinspired Copper Complexes: From Model Substrate to Extended Polysaccharides

Ligand–Copper(I) Primary O₂-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides

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Fenton-like Chemistry by a Copper(I) Complex and H2O2 Relevant to Enzyme Peroxygenase C–H Hydroxylation

Cited by 24 publications

References 91 publications

Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

Unraveling the Valence State and Reactivity of Copper Centers in Membrane-Bound Particulate Methane Monooxygenase

LPMO‐like Activity of Bioinspired Copper Complexes: From Model Substrate to Extended Polysaccharides

Ligand–Copper(I) Primary O2-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides

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Product

Resources

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Fenton-like Chemistry by a Copper(I) Complex and H₂O₂ Relevant to Enzyme Peroxygenase C–H Hydroxylation

Ligand–Copper(I) Primary O₂-Adducts: Design, Characterization, and Biological Significance of Cupric–Superoxides