Proton-coupled Electron Transfer Research Articles

Confinement effect of FeMOFs glass enhances the proton coupled electron transfer reaction for the organic pollutants polymerization toward sustainable water purification

Polymerization-driven removal of pollutants in advanced oxidation processes (AOPs) offers a sustainable way for the simultaneous achievement of contamination abatement and resource recovery, supporting a low-carbon water purification approach. In this work, metal–organic frameworks (MOFs) glass complexes (g-ZIF-62@8) were used as a platform to enhance proton transfer through the confinement effect of nanopores, modulating proton coupled electron transfer (PCET) reaction to promote organic pollutant polymerization. The results show that the confinement effect of nanopores in ZIF-62 glass can significantly improve the proton and electron transfer behavior, the proton diffusion coefficient is increased by 4.9 times (2.91*10−3 to 1.43*10−2), the energy barrier of the PCET reaction can be reduced by 1.9 eV, and the reaction kinetic rate constant is increased from 0.0198 min−1 to 0.20118 min−1. Photogenerated holes and Fe(IV = O), as the main reactive oxygen species (ROS), undergo PCET reaction with Bisphenol A (BPA) to convert them into phenoxy radicals, which are then polymerized into macromolecular organic compounds. PCET with proton-electron synergy was identified as a key driver of pollutant polymerization. This enables low-carbon purification and organic carbon recovery in wastewater. Our work provides new insights into the application of confinement effects to enhance proton and electron behavior to regulate pollutant polymerization toward sustainable water purification.

Tuning the Thermochemistry and Reactivity of a Series of Cu-Based 4H+/4e- Electron-Coupled-Proton Buffers.

Electron-coupled-proton buffers (ECPBs) store and deliver protons and electrons in a reversible fashion. We have recently reported an ECPB based on Cu and a redox-active ligand that promoted 4H+/4e- reversible transformations (J. Am. Chem. Soc. 2022, 144, 16905). Herein, we report a series of Cu-based ECPBs in which the ability of these to accept and/or donate H• equivalents can be tuned via ligand modification. The thermochemistry of the 4H+/4e- ECPB equilibrium was determined using open-circuit potential measurements. The reactivity of the ECPBs against proton-coupled electron transfer (PCET) reagents was also analyzed, and the results obtained were rationalized based on the thermochemical parameters. Experimental and computational analysis of the thermochemistry of the H+/e- transfers involved in the 4H+/4e- ECPB transformations found substantial differences between the stepwise (namely, BDFE1, BDFE2, BDFE3, and BDFE4) and average bond dissociation free energy values (BDFEavg.). Our analysis suggests that this "redox unleveling" is critical to promoting the disproportionation and ligand-exchange reactions involved in the 4H+/4e- ECPB equilibria. The difference in BDFEavg. within the series of Cu-based ECPBs was found to arise from a substantial change in the redox potential (E1/2) upon modification of the ligand scaffold, which is not fully compensated for by a change in the acidity/basicity (pKa), suggesting "thermochemical decompensation".

Triplet State Radical Chemistry: Significance of the Reaction of 3SO2 with HCOOH and HNO3.

The triplet excited states of sulfur dioxide can be accessed in the UV region and have a lifetime large enough that they can react with atmospheric trace gases. In this work, we report high level ab initio calculations for the reaction of the a3B1 and b3A2 excited states of SO2 with weak and strong acidic species such as HCOOH and HNO3, aimed to extend the chemistry reported in previous studies with nonacidic H atoms (water and alkanes). The reactions investigated in this work are very versatile and follow different kinds of mechanisms, namely, proton-coupled electron transfer (pcet) and conventional hydrogen atom transfer (hat) mechanisms. The study provides new insights into a general and very important class of excited-state-promoted reactions, opening up interesting chemical perspectives for technological applications of photoinduced H-transfer reactions. It also reveals that atmospheric triplet chemistry is more significant than previously thought.

A tetrahedral neptunium(V) complex.

Neptunium is an actinide element sourced from anthropogenic production, and, unlike naturally abundant uranium, its coordination chemistry is not well developed in all accessible oxidation states. High-valent neptunium generally requires stabilization from at least one metal-ligand multiple bond, and departing from this structural motif poses a considerable challenge. Here we report a tetrahedral molecular neptunium(V) complex ([Np5+(NPC)4][B(ArF5)4], 1-Np) (NPC = [NPtBu(pyrr)2]-; tBu = C(CH3)3; pyrr = pyrrolidinyl (N(C2H4)2); B(ArF5)4 = tetrakis(2,3,4,5,6-pentafluourophenyl)borate). Single-crystal X-ray diffraction, solution-state spectroscopy and density functional theory studies of 1-Np and the product of its proton-coupled electron transfer (PCET) reaction, 2-Np, demonstrate the unique bonding that stabilizes this reactive ion and establishes the thermochemical and kinetic parameters of PCET in a condensed-phase transuranic complex. The isolation of this four-coordinate, neptunium(V) complex reveals a fundamental reaction pathway in transuranic chemistry.

Bioinspired Water Preorganization in Confined Space for Efficient Water Oxidation Catalysis in Metallosupramolecular Ruthenium Architectures.

ConspectusNature has established a sustainable way to maintain aerobic life on earth by inventing one of the most sophisticated biological processes, namely, natural photosynthesis, which delivers us with organic matter and molecular oxygen derived from the two abundant resources sunlight and water. The thermodynamically demanding photosynthetic water splitting is catalyzed by the oxygen-evolving complex in photosystem II (OEC-PSII), which comprises a distorted tetramanganese-calcium cluster (CaMn4O5) as catalytic core. As an ubiquitous concept for fine-tuning and regulating the reactivity of the active site of metalloenzymes, the surrounding protein domain creates a sophisticated environment that promotes substrate preorganization through secondary, noncovalent interactions such as hydrogen bonding or electrostatic interactions. Based on the high-resolution X-ray structure of PSII, several water channels were identified near the active site, which are filled with extensive hydrogen-bonding networks of preorganized water molecules, connecting the OEC with the protein surface. As an integral part of the outer coordination sphere of natural metalloenzymes, these channels control the substrate and product delivery, carefully regulate the proton flow by promoting pivotal proton-coupled electron transfer processes, and simultaneously stabilize short-lived oxidized intermediates, thus highlighting the importance of an ordered water network for the remarkable efficiency of the natural OEC.Transferring this concept from nature to the engineering of artificial metal catalysts for fuel production has fostered the fascinating field of metallosupramolecular chemistry by generating defined cavities that conceptually mimic enzymatic pockets. However, the application of supramolecular approaches to generate artificial water oxidation catalysts remained scarce prior to our initial reports, since such molecular design strategies for efficient activation of substrate water molecules in confined nanoenvironments were lacking. In this Account, we describe our research efforts on combining the state-of-the art Ru(bda) catalytic framework with structurally programmed ditopic ligands to guide the water oxidation process in defined metallosupramolecular assemblies in spatial proximity. We will elucidate the governing factors that control the quality of hydrogen-bonding water networks in multinuclear cavities of varying sizes and geometries to obtain high-performance, state-of-the-art water oxidation catalysts. Pushing the boundaries of artificial catalyst design, embedding a single catalytic Ru center into a well-defined molecular pocket enabled sophisticated water preorganization in front of the active site through an encoded basic recognition site, resulting in high catalytic rates comparable to those of the natural counterpart OEC-PSII.To fully explore their potential for solar fuel devices, the suitability of our metallosupramolecular assemblies was demonstrated under (electro)chemical and photocatalytic water oxidation conditions. In addition, testing the limits of structural diversity allowed the fabrication of self-assembled linear coordination oligomers as novel photocatalytic materials and long-range ordered covalent organic framework (COF) materials as recyclable and long-term stable solid-state materials for future applications.

Local Electric Fields Drives the Proton-Coupled Electron Transfer within Cytochrome P450 Reductase

Local Electric Fields Drives the Proton-Coupled Electron Transfer within Cytochrome P450 Reductase

Synergistic Al-Al Dual-Atomic Site for Efficient Artificial Nitrogen Fixation.

Synthesis of ammonia by electrochemical nitrogen reduction reaction (NRR) is a promising alternative to the Haber-Bosch process. However, it is commonly obstructed by the high activation energy. Here, we report the design and synthesis of an Al-Al bonded dual atomic catalyst stabilized within an amorphous nitrogen-doped porous carbon matrix (Al2NC) with high NRR performance. The dual atomic Al2-sites act synergistically to catalyze the complex multiple steps of NRR through adsorption and activation, enhancing the proton-coupled electron transfer. This Al2NC catalyst exhibits a high Faradaic efficiency of 16.56±0.3 % with a yield rate of 29.22±1.2 μg h-1 mgcat -1. The dual atomic Al2NC catalyst shows long-term repeatable, and stable NRR performance. This work presents an insight into the identification of synergistic dual atomic catalytic site and mechanistic pathway for the electrochemical conversion of N2 to NH3.

Interfacial Proton-Coupled Electron Transfer via Localized Trap States on Metal Oxide Surfaces

Interfacial Proton-Coupled Electron Transfer via Localized Trap States on Metal Oxide Surfaces

Intercalated and Surface-Adsorbed Phosphate Anions in NiFe Layered Double-Hydroxide Catalysts Synergistically Enhancing Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER), a crucial semireaction in water electrolysis and rechargeable metal-air batteries, is vital for carbon neutrality. Hindered by a slow proton-coupled electron transfer, an efficient catalyst activating the formation of an O-H bond is essential. Here, we proposed a straightforward one-step hydrothermal procedure for fabricating PO43--modified NiFe layered double-hydroxide (NiFe LDH) catalysts and investigated the role of PO43- anions in enhancing OER. Phosphate amounts can efficiently regulate LDH morphology, crystallinity, composition, and electronic configuration. The optimized sample showed a low overpotential of 267 mV at 10 mA cm-2. Density functional theory calculations revealed that intercalated and surface-adsorbed PO43- anions in NiFe LDH reduced the Gibbs free energy in the rate-determining step of *OOH formation, balancing oxygen-containing intermediate adsorption/dissociation and promoting the OER. Intercalated phosphate ions accelerated precatalyst dehydrogenation kinetics, leading to a rapid reconstruction into active NiFe oxyhydroxide species. Surface-adsorbed PO43- interacted favorably with adsorbed *OOH on the active Ni sites, stabilizing *OOH. Overall, the synergistic effects of intercalated and surface-adsorbed PO43- anions significantly contributed to enhanced OER activity. Achieving optimal catalytic activity requires a delicate equilibrium between thermodynamic and kinetic factors by meticulously regulating the quantity of introduced PO43- ions. This endeavor will facilitate a deeper comprehension of the influence of anions in electrocatalysis for OER.

Oxidation mechanism of iodate to metaperiodate on a tungsten trioxide photoanode

The mechanisms involved in the photoelectrochemical oxidation of iodate (IO3−) to metaperiodate (IO4−) and H2O to O2 on WO3 were investigated using density functional theory. The oxygen evolution reaction (OER) included four proton-coupled electron transfer (PCET) steps via H2O2 intermediates. After the first PCET of the rate-limiting step, instead of H2O adsorption, IO3− was adsorbed and the second PCET step generated IO4− species (PI1 mechanism). Although another mechanism, PI2, with the two PCET steps followed by the IO3− adsorption was found, IO4− was energetically generated via PI1 rather than via PI2. Based on the free energy changes in the PCET steps, alkaline cations such as Li+, Na+, and K+ on WO3 suppressed the OER process. In addition, Na+ promoted the IO3− adsorption and subsequent PCET step of PI1. The computational results verified that using NaIO3 aqueous solution on WO3 effectively inhibits OER and facilitates IO4− generation, resulting in a higher (lower) selectivity of IO4− (O2) than using LiIO3 and KIO3 aqueous solutions.

Towards Immobilized Proton-Coupled Electron Transfer Agents for Electrochemical Carbon Capture from Air and Seawater

Electrochemical CO2 separation has drawn attention as a promising strategy for using renewable energy to mitigate climate change. Redox-active compounds that undergo proton-coupled electron transfer (PCET) are an impetus for pH-swing-driven CO2 capture at low energetic costs. However, multiple barriers hinder this technology from maturing, including sensitivity to oxygen and the slow kinetics of CO2 capture. Here, we use vapor phase chemistry to construct a textile electrode comprising an immobilized PCET agent, poly(1-aminoanthraquinone) (PAAQ), and incorporate it into redox flow cells. This design contrasts with others that use dissolved PCET agents by confining proton-storage to the surface of an electrode kept separate from an aqueous, CO2-capturing phase. This system facilitates carbon capture from gaseous sources (a 1% CO2 feed and air), as well as seawater, with the latter at an energetic cost of 202 kJ/molCO2, and we find that quinone moieties embedded within the electrode are more stable to oxygen than dissolved counterparts. Simulations using a 1D reaction-transport model show that moderate energetic costs should be possible for air capture of CO2 with higher loadings of polymer-bound PCET moieties. The remarkable stability of this system sets the stage for producing textile-based electrodes that facilitate pH-swing-driven carbon capture in practical situations.

Transient spectroscopic insights into nitroindole’s T1 state: Elucidating its intermediates and unique photochemical properties

Indoles are notable for their distinct photophysical and photochemical properties, making them useful indicators in biological systems and promising candidates for a variety of pharmaceutical applications. While some indoles exhibit room temperature phosphorescence, such a phenomenon has not been observed in nitroindoles. Typically, adding of a nitro group into aromatic compounds promotes ultrafast intersystem crossing and increases the formation quantum yield of the lowest excited triplet (T1). Therefore, understanding the reactivity of nitroindoles′ T1 states is imperative. This study investigated the physical properties and chemical reactivities of the T1 state of 6-nitroindole (3HN-6NO2) in both polar aprotic and protic solvents, using transient absorption spectroscopy. Our results demonstrate the basicity and acidity of 3HN-6NO2, emphasizing its potential for protonation and dissociation in mildly acidic and basic conditions, respectively. Furthermore, 3HN-6NO2 has a high oxidizing capacity, participating in electron transfer reactions and proton-coupled electron transfer to produce radicals. Interestingly, in protic solvents like alcohols, 3HN-6NO2 dissociates at the –NH group and forms N-H…O hydrogen-bonded complexes with the nitro group. By identifying transient absorption spectra of intermediates and quantifying kinetic reaction rate constants, we illuminate the unique properties of the T1 state nitroindoles, enriching our understanding of their photophysical and photochemical behaviors. The results of this study have significant implications for their potential application in both biological systems and materials science.

Selective Reduction of Triple Bond via Proton-Coupled Electron Transfer for the Synthesis of α,β-Unsaturated γ-Lactams.

Described herein is the development of a visible-light-induced photoredox 1,6-enyne reductive cyclization via selective reduction of a triple bond instead of an activated double bond. The selective 1,6-enyne radical cyclization/carbon═carbon double bond cleavage provided a straightforward route to structurally valuable α,β-unsaturated γ-lactams. TEMPO-trap experiments, control experiments, and DFT calculations have offered evidence supporting the possible catalytic cycle.

Intermolecular Proton-Coupled Electron Transfer Reactivity from a Persistent Charge-Transfer State for Reductive Photoelectrocatalysis.

Interest in applying proton-coupled electron transfer (PCET) reagents in reductive electro- and photocatalysis requires strategies that mitigate the competing hydrogen evolution reaction. Photoexcitation of a PCET donor to a charge-separated state (CSS) can produce a powerful H-atom donor capable of being electrochemically recycled at a comparatively anodic potential corresponding to its ground state. However, the challenge is designing a mediator with a sufficiently long-lived excited state for bimolecular reactivity. Here, we describe a powerful ferrocene-derived photoelectrochemical PCET mediator exhibiting an unusually long-lived CSS (τ ∼ 0.9 μs). In addition to detailed photophysical studies, proof-of-concept stoichiometric and catalytic proton-coupled reductive transformations are presented, which illustrate the promise of this approach.

Axial Ligation Impedes Proton-Coupled Electron-Transfer Reactivity of a Synthetic Compound-I Analogue.

The nature of the axial ligand in high-valent iron-oxo heme enzyme intermediates and related synthetic catalysts is a critical structural element for controlling proton-coupled electron-transfer (PCET) reactivity of these species. Herein, we describe the generation and characterization of three new 6-coordinate, iron(IV)-oxo porphyrinoid-π-cation-radical complexes and report their PCET reactivity together with a previously published 5-coordinate analogue, FeIV(O)(TBP8Cz+•) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3-) (2) (Cho, K. A high-valent iron-oxo corrolazine activates C-H bonds via hydrogen-atom transfer. J. Am. Chem. Soc. 2012, 134, 7392-7399). The new complexes FeIV(O)(TBP8Cz+•)(L) (L = 1-methyl imidazole (1-MeIm) (4a), 4-dimethylaminopyridine (DMAP) (4b), cyanide (CN-)(4c)) can be generated from either oxidation of the ferric precursors or by addition of L to the Compound-I (Cpd-I) analogue at low temperatures. These complexes were characterized by UV-vis, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies, and cryospray ionization mass spectrometry (CSI-MS). Kinetic studies using 4-OMe-TEMPOH as a test substrate indicate that coordination of a sixth axial ligand dramatically lowers the PCET reactivity of the Cpd-I analogue (rates up to 7000 times slower). Extensive density functional theory (DFT) calculations together with the experimental data show that the trend in reactivity with the axial ligands does not correlate with the thermodynamic driving force for these reactions or the calculated strengths of the O-H bonds being formed in the FeIV(O-H) products, pointing to non-Bell-Evans-Polanyi behavior. However, the PCET reactivity does follow a trend with the bracketed reduction potential of Cpd-I analogues and calculated electron affinities. The combined data suggest a concerted mechanism (a concerted proton electron transfer (CPET)) and an asynchronous movement of the electron/proton pair in the transition state.

XMECP: Reaching State-of-the-Art MECP Optimization in Multiscale Complex Systems.

The Python-based program, XMECP, is developed for realizing robust, efficient, and state-of-the-art minimum energy crossing point (MECP) optimization in multiscale complex systems. This article introduces the basic capabilities of the XMECP program by theoretically investigating the MECP mechanism of several example systems including (1) the photosensitization mechanism of benzophenone, (2) photoinduced proton-coupled electron transfer in the cytosine-guanine base pair in DNA, (3) the spin-flip process in oxygen activation catalyzed by an iron-containing 2-oxoglutarate-dependent oxygenase (Fe/2OGX), and (4) the photochemical pathway of flavoprotein adjusted by the intensity of an external electric field. MECPs related to multistate reaction and multistate reactivity in large-scale complex biochemical systems can be well-treated by workflows suggested by the XMECP program. The branching plane updating the MECP optimization algorithm is strongly recommended as it provides derivative coupling vector (DCV) with explicit calculation and can equivalently evaluate contributions from non-QM residues to DCV, which can be nonadiabatic coupling or spin-orbit coupling in different cases. In the discussed QM/MM examples, we also found that the influence on the QM region by DCV can occur through noncovalent interactions and decay with distance. In the example of DNA base pairs, the nonadiabatic coupling occurs across the π-π stacking structure formed in the double-helix system. In contrast to general intuition, in the example of Fe/2OGX, the central ferrous and oxygen part contribute little to the spin-orbit coupling; however, a nearby arginine residue, which is treated by molecular mechanics in the QM/MM method, contributes significantly via two hydrogen bonds formed with α-ketoglutarate (α-KG). This indicates that the arginine residue plays a significant role in oxygen activation, driving the initial triplet state toward the productive quintet state, which is more than the previous knowledge that the arginine residue can bind α-KG at the reaction site by hydrogen bonds.

Catalytic, Spectroscopic, and Theoretical Studies of Fe4S4-Based Coordination Polymers as Heterogenous Coupled Proton-Electron Transfer Mediators for Electrocatalysis.

Iron-sulfur clusters play essential roles in biological systems, and thus synthetic [Fe4S4] clusters have been an area of active research. Recent studies have demonstrated that soluble [Fe4S4] clusters can serve as net H atom transfer mediators, improving the activity and selectivity of a homogeneous Mn CO2 reduction catalyst. Here, we demonstrate that incorporating these [Fe4S4] clusters into a coordination polymer enables heterogeneous H atom transfer from an electrode surface to a Mn complex dissolved in solution. A previously reported solution-processable Fe4S4-based coordination polymer was successfully deposited on the surfaces of different electrodes. The coated electrodes serve as H atom transfer mediators to a soluble Mn CO2 reduction catalyst displaying good product selectivity for formic acid. Furthermore, these electrodes are recyclable with a minimal decrease in activity after multiple catalytic cycles. The heterogenization of the mediator also enables the characterization of solution-phase and electrode surface species separately. Surface enhanced infrared absorption spectroscopy (SEIRAS) reveals spectroscopic signatures for an in situ generated active Mn-H species, providing a more complete mechanistic picture for this system. The active species, reaction mechanism, and the protonation sites on the [Fe4S4] clusters were further confirmed by density functional theory calculations. The observed H atom transfer reactivity of these coordination polymer-coated electrodes motivates additional applications of this composite material in reductive H atom transfer electrocatalysis.

Diastereoselective Dearomatizing Cyclizations of 5-Arylpentan-2-ones by Samarium Diiodide - A Computational Analysis.

This study analyzes the samarium diiodide-promoted cyclizations of 5-arylpentan-2-ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer to the carbonyl group, which occurs synchronously with the rate determining cyclization event, and a second subsequent proton-coupled electron transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f-electrons of samarium. Comparison of the energies of the possible final products rules out thermodynamic control of the observed regio- and diastereoselectivities. Kinetic control via appropriate transition states is correctly predicted, but to obtain reasonable energy levels the influence of the co-solvent hexamethylphosphortriamide has to be estimated by using a correction term. The steric effect of the bulky samarium ligands is decisive for the observed stereoselectivity. Carbonyl groups in para-position of the aryl group change the regioselectivity of the cyclization and lead to spiro compounds. The computations suggest again kinetic control of this deviating outcome. However, the standard mechanism has to be modified and the involvement of a complex activated by two SmI2 moieties is proposed in which two electrons are transferred simultaneously to form the new C-C bond. Computation of model intermediates show the feasibility of this alternative+ mechanism.

Computational screening of PCP-type pincer ligands for Mo-catalyzed nitrogen fixation

Abstract Computational screening of N-heterocyclic carbene-based PCP-type pincer ligands (PCP = 1,3-bis(di-tert-buthylphosphinomethyl)benzimidazole-2-ylidene) has been performed for the design of molybdenum-based molecular catalysts for nitrogen fixation. Previously, we theoretically and experimentally demonstrated that the introduction of electron-donating/withdrawing substituents to the original PCP ligand is a promising way to control the catalytic activity. Here, we investigate electronic and energetic properties of nitrogenous Mo intermediates bearing 40 substituted PCP ligands [MoI(NHx)(R-PCP)] (x = 1 to 3) that are involved in the rate-determining step in our proposed catalytic mechanism. Electron-withdrawing substituents enhance the π-accepting ability of R-PCP and effectively stabilize the lowest unoccupied molecular orbital (LUMO) of the corresponding Mo–nitride (Mo≡N) complexes, which is expected to be advantageous for the transformation of the nitride N atom via proton-coupled electron transfer. The introduction of strong electron-withdrawing substituents to the PCP ligand also increases the N–H bond energy of [MoI(NHx)(R-PCP)] evaluated using the bond dissociation free energy and the bond dissociation enthalpy. As a result of the computational screening, we newly propose an alternative strategy for designing PCP ligands with high π-accepting ability: the extension of the π-conjugated system of the PCP ligand by introducing fused benzene rings.

An Active Site Tyr Residue Guides the Regioselectivity of Lysine Hydroxylation by Nonheme Iron Lysine-4-hydroxylase Enzymes through Proton-Coupled Electron Transfer.

Lysine dioxygenase (KDO) is an important enzyme in human physiology involved in bioprocesses that trigger collagen cross-linking and blood pressure control. There are several KDOs in nature; however, little is known about the factors that govern the regio- and stereoselectivity of these enzymes. To understand how KDOs can selectively hydroxylate their substrate, we did a comprehensive computational study into the mechanisms and features of 4-lysine dioxygenase. In particular, we selected a snapshot from the MD simulation on KDO5 and created large QM cluster models (A, B, and C) containing 297, 312, and 407 atoms, respectively. The largest model predicts regioselectivity that matches experimental observation with rate-determining hydrogen atom abstraction from the C4-H position, followed by fast OH rebound to form 4-hydroxylysine products. The calculations show that in model C, the dipole moment is positioned along the C4-H bond of the substrate and, therefore, the electrostatic and electric field perturbations of the protein assist the enzyme in creating C4-H hydroxylation selectivity. Furthermore, an active site Tyr233 residue is identified that reacts through proton-coupled electron transfer akin to the axial Trp residue in cytochrome c peroxidase. Thus, upon formation of the iron(IV)-oxo species in the catalytic cycle, the Tyr233 phenol loses a proton to the nearby Asp179 residue, while at the same time, an electron is transferred to the iron to create an iron(III)-oxo active species. This charged tyrosyl residue directs the dipole moment along the C4-H bond of the substrate and guides the selectivity to the C4-hydroxylation of the substrate.