Subtopic Deep Dive

Proton-Coupled Electron Transfer in Oxygenation
Research Guide

What is Proton-Coupled Electron Transfer in Oxygenation?

Proton-coupled electron transfer (PCET) in oxygenation refers to concerted proton and electron movement facilitating O-O bond formation and cleavage in metal-catalyzed reactions within enzymes and synthetic models.

PCET processes drive multi-electron oxygen chemistry in systems like ribonucleotide reductase and photosystem II, with experimental focus on H/D isotope effects and pH dependencies. Theoretical studies model gating mechanisms in metalloenzymes. Over 20 papers from 1973-2020 explore these dynamics, including Stiefel (1973, 129 citations) on molybdenum enzymes and Nam et al. (2018, 122 citations) on nonheme metal-oxygen intermediates.

15
Curated Papers
3
Key Challenges

Why It Matters

PCET enables efficient O2 reduction in artificial photosynthesis devices, mimicking photosystem II for solar fuel production (Hohenberger et al., 2012, 528 citations). In energy storage, PCET principles guide battery electrocatalysts by controlling O-O bond cleavage potentials (Nam et al., 2018). Synthetic models inform catalyst design for selective oxygenation in pharmaceutical synthesis (de Visser et al., 2013, 110 citations).

Key Research Challenges

Modeling Concerted PCET

Capturing synchronous proton-electron transfer requires multiscale QM/MM methods to handle solvent and protein effects accurately. Challenges persist in predicting pH-dependent kinetics (Ahmadi et al., 2018, 177 citations). H/D isotope effects demand precise vibrational analysis.

Gating Mechanism Elucidation

Identifying proton relays and electrostatic gating in O-O bond formation remains unresolved experimentally. Computational models struggle with transition state barriers in nonheme iron systems (Nam et al., 2018, 122 citations). Validation against kinetic data is limited.

High-Valent Intermediate Stability

Stabilizing iron-oxo species for PCET reactivity faces spin-state crossing issues in DFT calculations. Synthetic mimics show poor correlation with enzymatic turnover (Hohenberger et al., 2012, 528 citations). Scalability to biomimetic catalysis is hindered.

Essential Papers

1.

The biology and chemistry of high-valent iron–oxo and iron–nitrido complexes

Johannes Hohenberger, Kallol Ray, Karsten Meyer · 2012 · Nature Communications · 528 citations

2.

Conservation and diversity of radiation and oxidative stress resistance mechanisms in<i>Deinococcus</i>species

Sangyong Lim, Jong‐Hyun Jung, Laurence Blanchard et al. · 2018 · FEMS Microbiology Reviews · 206 citations

Deinococcus bacteria are famous for their extreme resistance to ionising radiation and other DNA damage- and oxidative stress-generating agents. More than a hundred genes have been reported to cont...

3.

Multiscale modeling of enzymes: QM‐cluster, QM/MM, and QM/MM/MD: A tutorial review

Shideh Ahmadi, Lizandra Barrios Herrera, Morteza Chehelamirani et al. · 2018 · International Journal of Quantum Chemistry · 177 citations

Abstract Exemplars of the state of the art in modeling enzymes are reviewed through a selection of works from leading schools using QM‐only cluster models, QM/MM models and QM/MM/MD models. A compu...

4.

Structure, function, and biosynthesis of nickel‐dependent enzymes

Marila Alfano, Christine Cavazza · 2020 · Protein Science · 166 citations

Abstract Nickel enzymes, present in archaea, bacteria, plants, and primitive eukaryotes are divided into redox and nonredox enzymes and play key functions in diverse metabolic processes, such as en...

5.

The [Fe-Fe]-Hydrogenase Maturation Protein HydF from Thermotoga maritima Is a GTPase with an Iron-Sulfur Cluster

Xavier Brazzolotto, Jon K. Rubach, Jacques Gaillard et al. · 2005 · Journal of Biological Chemistry · 137 citations

6.

Proposed Molecular Mechanism for the Action of Molybdenum in Enzymes: Coupled Proton and Electron Transfer

Edward I. Stiefel · 1973 · Proceedings of the National Academy of Sciences · 129 citations

The reactions catalyzed by Mo enzymes each find the product differing from the substrate by two electrons and two protons (or some multiple thereof). The coordination chemistry of Mo suggests that ...

7.

Hydrogen Atom Transfer Reactions of Mononuclear Nonheme Metal–Oxygen Intermediates

Wonwoo Nam, Yong‐Min Lee, Shunichi Fukuzumi · 2018 · Accounts of Chemical Research · 122 citations

Molecular oxygen (O<sub>2</sub>), the greenest oxidant, is kinetically stable in the oxidation of organic substrates due to its triplet ground state. In nature, O<sub>2</sub> is reduced by two elec...

Reading Guide

Foundational Papers

Start with Stiefel (1973) for core Mo-PCET mechanism, Hohenberger et al. (2012) for iron-oxo reactivity, and de Visser et al. (2013) for QM/MM modeling benchmarks.

Recent Advances

Study Nam et al. (2018) for nonheme HAT dynamics and Bím et al. (2018) for thermodynamic contributions beyond classical potentials.

Core Methods

QM/MM (Ahmadi et al., 2018), DFT for spin-state reactivity (Hohenberger et al., 2012), kinetic analysis of H/D effects and pH dependencies.

How PapersFlow Helps You Research Proton-Coupled Electron Transfer in Oxygenation

Discover & Search

Research Agent uses searchPapers('proton-coupled electron transfer oxygenation') to retrieve Stiefel (1973), citationGraph on Hohenberger et al. (2012) reveals 528 downstream citations in PCET models, findSimilarPapers expands to de Visser et al. (2013), and exaSearch uncovers pH-dependent kinetics papers.

Analyze & Verify

Analysis Agent applies readPaperContent on Nam et al. (2018) to extract HAT reactivity data, verifyResponse(CoVe) cross-checks PCET mechanisms against Hohenberger et al. (2012), runPythonAnalysis plots H/D isotope effects from kinetic datasets with NumPy, and GRADE assigns A-grade evidence to QM/MM validations (Ahmadi et al., 2018).

Synthesize & Write

Synthesis Agent detects gaps in gating mechanisms across Stiefel (1973) and Nam et al. (2018), flags contradictions in spin states, Writing Agent uses latexEditText for reaction schemes, latexSyncCitations integrates 10 PCET papers, latexCompile generates publication-ready reviews, and exportMermaid diagrams O-O bond formation pathways.

Use Cases

"Analyze H/D kinetic isotope effects in PCET for iron-oxo oxygenation from Nam et al. 2018."

Analysis Agent → readPaperContent(Nam 2018) → runPythonAnalysis(KIE data extraction, NumPy fitting) → matplotlib plot of rate ratios.

"Write LaTeX review on molybdenum PCET mechanisms citing Stiefel 1973 and recent models."

Synthesis Agent → gap detection(Stiefel 1973) → Writing Agent → latexEditText(draft) → latexSyncCitations(5 papers) → latexCompile(PDF output).

"Find GitHub code for QM/MM simulations of PCET in oxygenation enzymes."

Research Agent → paperExtractUrls(Ahmadi 2018) → paperFindGithubRepo(QM/MM PCET) → githubRepoInspect(scripts for ORCA/Gaussian inputs).

Automated Workflows

Deep Research workflow scans 50+ PCET papers via searchPapers, builds citationGraph from Hohenberger (2012), and outputs structured report on O-O activation. DeepScan applies 7-step CoVe to verify Nam et al. (2018) HAT claims against experimental data. Theorizer generates hypotheses on gating from Stiefel (1973) and de Visser (2013) mechanisms.

Frequently Asked Questions

What defines PCET in metal-catalyzed oxygenation?

PCET involves coupled proton and electron transfer enabling O-O bond formation/cleavage, as in Stiefel (1973) for Mo enzymes differing by 2e-/2H+.

What are key methods for studying PCET?

QM/MM modeling (Ahmadi et al., 2018), kinetic isotope effects, and pH titrations probe concerted transfers; DFT optimizes high-valent intermediates (Nam et al., 2018).

What are seminal papers on this topic?

Hohenberger et al. (2012, 528 citations) on iron-oxo PCET; Stiefel (1973, 129 citations) on Mo enzyme mechanisms; de Visser et al. (2013, 110 citations) on computational enzyme models.

What open problems exist in PCET oxygenation?

Unresolved gating mechanisms, accurate prediction of pH-dependent barriers, and bridging synthetic models to enzymatic efficiency (Bím et al., 2018).

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