Redox-Triggered Proton Transfer in Synthetic Models for Non-Heme Diiron Enzymes: Spectroscopic, Computational, and Mechanistic Insights.
- 1Department of Chemistry, University of California, 1102 Natural Sciences II, Irvine, California92697, United States.
- 2Department of Chemistry, Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania15213, United States.
Abstract
The transformations that occur at metalloenzyme active sites during catalysis are inextricably coupled to secondary-sphere interactions with surrounding amino acids and water molecules. Probing the elemental steps of these in vitro reactions remains a formidable challenge; their inherent catalytic velocity frequently prevents the isolation or detection of transient intermediates. Mapping distinct oxidation events, coupled with proton transfer steps, provides a clear pathway to elucidating these overarching catalytic mechanisms. High-valent iron-oxido and hydroxido species are key intermediates in oxidative processes catalyzed by nonheme iron proteins. Here, we employ structurally characterized bioinspired diiron complexes to systematically probe these elemental processes. We have spectroscopically characterized six distinct oxidation and protonation states of a single, asymmetric diiron core. Density functional theory calculations corroborate these findings, demonstrating strong agreement with the experimental electronic parameters and provide insight into the energetics governing individual electron and proton transfers. Reactivity profiling demonstrates that the synthesized FeIIIFeIV complex efficiently abstracts a hydrogen atom from a phenolic substrate via a proton-coupled electron transfer (PCET) pathway that takes advantage of secondary sphere hydrogen bond interactions provided by the ligand framework. This process mimics the native tyrosyl radical generation observed in intermediate X of RNR, a key enzyme in DNA biosynthesis.
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BibTeX
@article{lee2026redoxtriggered,
title = {{Redox-Triggered Proton Transfer in Synthetic Models for Non-Heme Diiron Enzymes: Spectroscopic, Computational, and Mechanistic Insights.}},
author = {Justin L Lee and Saborni Biswas and Victoria F Oswald and Joseph W Ziller and A S Borovik and Emile L Bominaar and Michael P Hendrich},
journal = {Inorganic chemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.inorgchem.6c04733},
url = {https://europepmc.org/article/MED/42916893},
note = {CC BY},
}
RIS
TY - JOUR
TI - Redox-Triggered Proton Transfer in Synthetic Models for Non-Heme Diiron Enzymes: Spectroscopic, Computational, and Mechanistic Insights.
AU - Justin L Lee
AU - Saborni Biswas
AU - Victoria F Oswald
AU - Joseph W Ziller
AU - A S Borovik
AU - Emile L Bominaar
AU - Michael P Hendrich
PY - 2026
DA - 2026/10/01
JO - Inorganic chemistry
DO - 10.1021/acs.inorgchem.6c04733
UR - https://europepmc.org/article/MED/42916893
AB - The transformations that occur at metalloenzyme active sites during catalysis are inextricably coupled to secondary-sphere interactions with surrounding amino acids and water molecules. Probing the elemental steps of these in vitro reactions remains a formidable challenge; their inherent catalytic velocity frequently prevents the isolation or detection of transient intermediates. Mapping distinct oxidation events, coupled with proton transfer steps, provides a clear pathway to elucidating these overarching catalytic mechanisms. High-valent iron-oxido and hydroxido species are key intermediates in oxidative processes catalyzed by nonheme iron proteins. Here, we employ structurally characterized bioinspired diiron complexes to systematically probe these elemental processes. We have spectroscopically characterized six distinct oxidation and protonation states of a single, asymmetric diiron core. Density functional theory calculations corroborate these findings, demonstrating strong agreement with the experimental electronic parameters and provide insight into the energetics governing individual electron and proton transfers. Reactivity profiling demonstrates that the synthesized FeIIIFeIV complex efficiently abstracts a hydrogen atom from a phenolic substrate via a proton-coupled electron transfer (PCET) pathway that takes advantage of secondary sphere hydrogen bond interactions provided by the ligand framework. This process mimics the native tyrosyl radical generation observed in intermediate X of RNR, a key enzyme in DNA biosynthesis.
SN - 0020-1669
SN - 1520-510X
ER -