Proton-coupled Electron Transfer Mechanism Research Articles

Circumventing Kinetic Barriers to Metal Hydride Formation with Metal-Ligand Cooperativity.

We report the two-electron, one-proton mechanism of cobalt hydride formation for the conversion of [CoIIICp(PPh2NBn2)(CH3CN)]2+ to [HCoIIICp(PPh2NBn2)]+. This complex catalytically converts CO2 to formate under CO2 reduction conditions, with hydride formation as a key elementary step. Through a combination of electrochemical measurements, digital simulations, theoretical calculations, and additional mechanistic and thermochemical studies, we outline the explicit role of the PPh2NBn2 ligand in the proton-coupled electron transfer (PCET) reactivity that leads to hydride formation. We reveal three unique PCET mechanisms, and we show that the amine on the PPh2NBn2 ligand serves as a kinetically accessible protonation site en route to the thermodynamically favored cobalt hydride. Cyclic voltammograms recorded with proton sources that span a wide range of pKa values show four distinct regimes where the mechanism changes as a function of acid strength, acid concentration, and timescale between electrochemical steps. Peak shift analysis was used to determine proton transfer rate constants where applicable. This work highlights the astute choices that must be made when designing catalytic systems, including the basicity and kinetic accessibility of protonation sites, acid strength, acid concentration, and timescale between electron transfer steps, to maximize catalyst stability and efficiency.

When a Twist Makes a Difference: Exploring PCET and ESIPT on a Nonplanar Hydrogen-Bonded Donor-Acceptor System.

Bioinspired benzimidazole-phenol constructs with an intramolecular hydrogen bond connecting the phenol and the benzimidazole have been synthesized to study both proton-coupled electron transfer (PCET) and excited-state intramolecular proton transfer (ESIPT) processes. Strategic incorporation of a methyl group disrupts the coplanarity between the aromatic units, causing a pronounced twist, weakening the intramolecular hydrogen bond, decreasing the phenol redox potential, reducing the chemical reversibility, and quenching the fluorescence emission. Infrared spectroelectrochemistry and transient absorption spectroscopy confirm the formation of the oxidized product upon PCET and probe excited-state relaxation mechanisms, respectively. Density functional theory calculations of redox potentials corroborate the experimental findings. Additionally, time-dependent density functional theory calculations uncover the fluorescence quenching mechanism, showing that the nonradiative twisted intramolecular charge transfer state responsible for fluorescence quenching is more energetically favorable in the methyl-substituted system. Incorporating groups causing steric hindrance expands the design of biomimetic systems capable of performing both PCET and ESIPT.

Reductive Photocatalytic Proton-Coupled Electron Transfer by a Zirconium-based Molecular Platform.

Reductive proton-coupled electron transfer (PCET) has important energetic implications in numerous synthetic and natural redox processes. The development of catalytic systems that can mediate such transformations has become an attractive target, especially when light is used to generate the reactive species towards solar-to-chemicals conversion. However, such approach becomes challenged by kinetic competition with H2 evolution. Here we describe the excited state reactivity of a molecular Zr-based platform under visible light irradiation for the efficient reduction of multiple bonds. Mechanistic investigations shine light on a charge separation process that colocalizes an excited electron and an acidic proton to promote selective PCET. We further leveraged this reactivity for the photocatalytic reduction of a variety of organic substrates. Our results demonstrate the promise of this molecular platform to design strong photocatalytic PCET mediators for reductive transformations. More broadly, we also show the potential relevance of PCET mechanisms in the (photo)redox chemistry of Zr-based molecular materials.

Reductive Photocatalytic Proton‐Coupled Electron Transfer by a Zirconium‐based Molecular Platform

Reductive proton‐coupled electron transfer (PCET) has important energetic implications in numerous synthetic and natural redox processes. The development of catalytic systems that can mediate such transformations has become an attractive target, especially when light is used to generate the reactive species towards solar‐to‐chemicals conversion. However, such approach becomes challenged by kinetic competition with H2 evolution. Here we describe the excited state reactivity of a molecular Zr‐based platform under visible light irradiation for the efficient reduction of multiple bonds. Mechanistic investigations shine light on a charge separation process that colocalizes an excited electron and an acidic proton to promote selective PCET. We further leveraged this reactivity for the photocatalytic reduction of a variety of organic substrates. Our results demonstrate the promise of this molecular platform to design strong photocatalytic PCET mediators for reductive transformations. More broadly, we also show the potential relevance of PCET mechanisms in the (photo)redox chemistry of Zr‐based molecular materials.

Reversed I1Cu4 single-atom sites for superior neutral ammonia electrosynthesis with nitrate

Electrochemical ammonia (NH3) synthesis from nitrate reduction (NITRR) offers an appealing solution for addressing environmental concerns and the energy crisis. However, most of the developed electrocatalysts reduce NO3- to NH3 via a hydrogen (H*)-mediated reduction mechanism, which suffers from undesired H*-H* dimerization to H2, resulting in unsatisfactory NH3 yields. Herein, we demonstrate that reversed I1Cu4 single-atom sites, prepared by anchoring iodine single atoms on the Cu surface, realized superior NITRR with a superior ammonia yield rate of 4.36 mg h-1 cm-2 and a Faradaic efficiency of 98.5% under neutral conditions via a proton-coupled electron transfer (PCET) mechanism, far beyond those of traditional Cu sites (NH3 yield rate of 0.082 mg h-1 cm-2 and Faradaic efficiency of 36.5%) and most of H*-mediated NITRR electrocatalysts. Theoretical calculations revealed that I single atoms can regulate the local electronic structures of adjacent Cu sites in favor of stronger O-end-bidentate NO3- adsorption with dual electron transfer channels and suppress the H* formation from the H2O dissociation, thus switching the NITRR mechanism from H*-mediated reduction to PCET. By integrating the monolithic I1Cu4 single-atom electrode into a flow-through device for continuous NITRR and in situ ammonia recovery, an industrial-level current density of 1 A cm-2 was achieved along with a NH3 yield rate of 69.4 mg h-1 cm-2. This study offers reversed single-atom sites for electrochemical ammonia synthesis with nitrate wastewater and sheds light on the importance of switching catalytic mechanisms in improving the performance of electrochemical reactions.

Conformational control over proton-coupled electron transfer in metalloenzymes.

From the reduction of dinitrogen to the oxidation of water, thechemical transformations catalysed by metalloenzymes underlie global geochemical and biochemical cycles. These reactions represent some of the most kinetically and thermodynamically challenging processes knownand require the complex choreography of the fundamental building blocks of nature, electrons and protons, to be carried out with utmost precision and accuracy. The rate-determining step of catalysis in many metalloenzymes consists of aprotein structural rearrangement, suggestingthat nature has evolved to leverage macroscopic changes in protein molecularstructure to control subatomicchanges in metallocofactor electronicstructure. The proton-coupled electron transfermechanisms operative in nitrogenase, photosystem II and ribonucleotide reductase exemplify this interplay between molecular and electronic structural control. We present the culmination of decades of study on each of these systems and clarify what is known regarding the interplay between structural changesand functional outcomes in these metalloenzyme linchpins.

Wavelength-Selective Xanthene-Based Monochromophoric Photoremovable Protecting Groups for Tuning Soft Matter Material Properties.

Photocontrolled deprotection of specific functional groups has garnered significant interest over the past two decades. Notably, the selective deprotection of distinct groups based on wavelength has emerged as a prominent focus in recent research. The achievement of this objective has primarily involved the utilization of linker-based bichromophoric systems and diverse cocktail mixtures of photoresponsive protecting groups (PRPGs), each responsive to varying wavelengths of light. Herein, we present the first wavelength-selective monochromophoric system based on a hydroxanthene moiety, enabling the wavelength-selective release of two distinct functionalities under 450 and 600 nm light, respectively. The mechanism of the wavelength-selective photodegradation was thoroughly investigated by 1H NMR, UV-vis, and fluorescence spectroscopy, suggesting a proton-coupled electron transfer mechanism in the first photorelease step and electron transfer based arylmethyl type of photorelease in the second step. The utility of the xanthene-based wavelength-selective PRPGs was demonstrated in the multistep degradation of microparticles and dual-color tuning of polymer chain architecture, thus opening an avenue to design advanced photoreactive wavelength-controlled systems for applications in soft matter materials.

Enhanced optical bistability of energy saving viologen-based electrochromic display with a commercial phenol-based epoxy resin

A highly bistable viologen-based electrochromic display was successfully developed by using a simple strategy with cheap commercial phenol-based epoxy. By adding epoxy, phenol species can contribute a dual effect, in which they can play as electron shuttles to facilitate fast coloration of ECDs and stabilize the long bistability of ECDs through the proton-coupled electron transfer (PCET) mechanism during coloration state. With the use of epoxy, CPHEV2+/E exhibits an improvement of maximum ΔT, which is 78.6 % at 596 nm compared to 53 % for that of ECD without epoxy. The ECD with added epoxy can hold the colored state up to 50 h after applying a voltage of −2.5 V for 15 s compared with ECD without epoxy which is 22 min. Notably, the color state undergoes decomposition to 10 % of its initial value after 3.5 h without any extra power supply. The 3D-printed rose flower ECD was successfully demonstrated using digital light processing (DLP) with good dimensional accuracy and resolution.

Influence of Catalyst Surface Structure on the Electrochemical Hydrogenation of Cis,Cis-Muconic Acid

Adipic acid (AA) production from petroleum-based cyclohexane is one of the largest chemical processes in terms of annual volumetric turnover accounting for 3 million tons as of 2022. The current commercial approach to synthesize AA is through the oxidation of petroleum-derived cyclohexane using nitric acid. The release of N2O in stoichiometric amounts makes it one of the most significant greenhouse gas (GhG) emitting processes. The abundance of biomass in the Midwestern United States has driven significant research efforts to synthesize bio-derived and sustainable commodity products and lower the chemical industry’s carbon footprint.1 cis,cis-Muconic acid (ccMA), a biobased C6 diunsaturated diacid platform molecule can be transformed to commodity chemicals like caprolactam, adipic acid, and terephthalic acid, with AA being of particular interest for the synthesis of nylon 6,6.2 For the first time in literature, we demonstrate appreciable production of AA (conversion: 91%, selectivity: >95%) through electrochemical hydrogenation (ECH) of ccMA on PGM catalysts. Carbon-supported palladium (Pd/C) and platinum (Pt/C) selectively produced AA while bulk Pd and Pt yielded the monounsaturated trans-3-hexenedioic acid (t3HDA) intermediate and H2 under all tested conditions. Such an influence of surface structure on the electrochemistry of organics is not unprecedented. Koper et. al3 studied Pt single crystals for the electrochemical hydrogenation of acetone and showed how activity, selectivity, and extent of catalytic poisoning are highly sensitive to the Pt surface structure. Similarly, we used density functional calculations to elucidate the structure-sensitive nature of ccMA ECH and its intermediates by identifying thermodynamically preferred reaction pathways as a function of surface geometry (terrace vs steps). The energetics coupled with experimental observations suggest that the reduction of ccMA to t3HDA occurs through an outer sphere proton-coupled electron transfer mechanism, while the reduction of HDA to AA preferentially occurs on Pd and Pt (111), the most abundant facet in Pd/C and Pt/C. Our calculations also explain the exceptional performance of Pd/C compared to Pt/C by the weaker binding of Pd terrace sites compared to Pt. Overall, combining renewable electricity, in-situ hydrogen generation from water, and a biologically-produced intermediate enabled us to open a sustainable route for bio-adipic acid production. This allows us to further design and optimize the catalyst for the selective production of biobased AA.

Proton-Coupled Electron Transfer Mechanisms for CO2 Reduction to Methanol Catalyzed by Surface-Immobilized Cobalt Phthalocyanine.

Immobilized cobalt phthalocyanine (CoPc) is a highly promising architecture for the six-proton, six-electron reduction of CO2 to methanol. This electroreduction process relies on proton-coupled electron transfer (PCET) reactions that can occur by sequential or concerted mechanisms. Immobilization on a conductive support such as carbon nanotubes or graphitic flakes can fundamentally alter the PCET mechanisms. We use density functional theory (DFT) calculations of CoPc adsorbed on an explicit graphitic surface model to investigate intermediates in the electroreduction of CO2 to methanol. Our calculations show that the alignment of the CoPc and graphitic electronic states influences the reductive chemistry. These calculations also distinguish between charging the graphitic surface and reducing the CoPc and adsorbed intermediates as electrons are added to the system. This analysis allows us to identify the chemical transformations that are likely to be concerted PCET, defined for these systems as the mechanism in which protonation of a CO2 reduction intermediate is accompanied by electron abstraction from the graphitic surface to the adsorbate without thermodynamically stable intermediates. This work establishes a mechanistic pathway for methanol production that is consistent with experimental observations and provides fundamental insight into how immobilization of the CoPc impacts its CO2 reduction chemistry.

Proton-Coupled Electron Transfer and Hydrogen Tunneling in Olive Oil Phenol Reactions.

Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer hydrogen to radicals. Proton-coupled electron transfer reactions and hydrogen tunneling are ubiquitous in biological systems. Reactions of olive oil phenols, hydroxytyrosol, tyrosol, oleuropein, oleacein, oleocanthal, homovanillyl alcohol, vanillin, and a few phenolic acids with a DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical in a 1,4-dioxane:water = 95:5 or 99:1 v/v solvent mixture were studied through an experimental kinetic analysis and computational chemistry calculations. The highest rate constants corresponding to the highest antioxidative activity are obtained for the ortho-diphenols hydroxytyrosol, oleuropein, and oleacein. The experimentally determined kinetic isotope effects (KIEs) for hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions are 16.0, 15.4, and 16.7, respectively. Based on these KIEs, thermodynamic activation parameters, and an intrinsic bond orbital (IBO) analysis along the IRC path calculations, we propose a proton-coupled electron transfer mechanism. The average local ionization energy and electron donor Fukui function obtained for the phenolic compounds show that the most reactive electron-donating sites are associated with π electrons above and below the aromatic ring, in support of the IBO analysis and proposed PCET reaction mechanism. Large KIEs and isotopic values of Arrhenius pre-exponential factor AH/AD determined for the hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions of 0.6, 1.3, and 0.3, respectively, reveal the involvement of hydrogen tunneling in the process.

A Unified Charge Storage Mechanism to Rationalize the Electrochemical Behavior of Quinone-Based Organic Electrodes in Aqueous Rechargeable Batteries.

Due to their eco-sustainability and versatility, organic electrodes are promising candidates for large-scale energy storage in rechargeable aqueous batteries. This is notably the case of aqueous hybrid batteries that pair the low voltage of a zinc anode with the high voltage of a quinone-based (or analogue of quinone-based) organic cathode. However, the mechanisms governing their charge-discharge cycles remain poorly understood and are even a matter of debate and controversy. No consensus exists on the charge carrier in mild aqueous electrolytes, especially when working in an electrolyte containing a multivalent metal cation such as Zn2+. In this study, we comprehensively investigate the electrochemical reactivity of two model quinones, chloranil, and duroquinone, either diluted in solution or incorporated into carbon-based composite electrodes. We demonstrate that a common nine-member square scheme proton-coupled electron transfer mechanism allows us to fully describe and rationalize their electrochemical behavior in relation to the pH and chemical composition of the aqueous electrolyte. Additionally, we highlight the crucial role played by the pKas associated with the reduced states of quinones in determining the nature of the charge carrier that compensates for the negative charges reversibly injected in the active material. Finally, contrary to the widely reported findings for Zn/organic batteries, we unequivocally establish that the predominant solid-state charge carriers in Zn2+-based mild aqueous electrolytes are not multivalent Zn2+ cations but rather protons supplied by the weakly acidic hexaaqua metal ions (i.e., [Zn(H2O)6]2+]).

Mechanism of Electrocatalytic H2 Evolution, Carbonyl Hydrogenation, and Carbon-Carbon Coupling on Cu.

Aqueous-phase electrocatalytic hydrogenation of benzaldehyde on Cu leads not only to benzyl alcohol (the carbonyl hydrogenation product), but Cu also catalyzes carbon-carbon coupling to hydrobenzoin. In the absence of an organic substrate, H2 evolution proceeds via the Volmer-Tafel mechanism on Cu/C, with the Tafel step being rate-determining. In the presence of benzaldehyde, the catalyst surface is primarily covered with the organic substrate, while H* coverage is low. Mechanistically, the first H addition to the carbonyl O of an adsorbed benzaldehyde molecule leads to a surface-bound hydroxy intermediate. The hydroxy intermediate then undergoes a second and rate-determining H addition to its α-C to form benzyl alcohol. The H additions occur predominantly via the proton-coupled electron transfer mechanism. In a parallel reaction, the radical α-C of the hydroxy intermediate attacks the electrophilic carbonyl C of a physisorbed benzaldehyde molecule to form the C-C bond, which is rate-determining. The C-C coupling is accompanied by the protonation of the formed alkoxy radical intermediate, coupled with electron transfer from the surface of Cu, to form hydrobenzoin.

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.

Proton-coupled electron transfer activation of peroxydisulfate with phosphorylated zero-valent iron

Heterogeneous peroxydisulfate (PDS) activation driven by conventional electron transfer (ET) is often frustrated by low thermodynamic driving force and sluggish kinetics. Herein, we propose a proton-coupled electron transfer (PCET) strategy of PDS activation, by utilizing ball-milled phosphorylated zero-valent iron (P-ZVIbm) as a PCET platform. P-ZVIbm efficiently activated PDS to produce SO4•− and •OH for rapid degradation of 4-chlorophenol in a wide pH range of 3.5–10.5, with rate constants 3–62 times those of the ZVIbm/PDS counterpart. PCET mechanism was evidenced by the pH dependent kinetics, kinetic isotope effect, and proton inventory study. The surface-bound phosphates offer flexible pendant protons (P-O-H) through hydrogen bonds, delocalizing electrons of peroxide O to polarize the O-O bond, thereby facilitating the ET from ZVI for O-O bond cleavage. The work demonstrates the superiority of PCET strategy for heterogeneous PDS activation, and shall guide the design of high-performance Fenton-like catalysts.

Unraveling a Concerted Proton-Coupled Electron Transfer Pathway in Atomically Precise Gold Nanoclusters.

Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.

An unexpected and robust nickel (II)-based ether-bonded homogeneous system: Effective for photocatalytic CO2-to-CO transformation in visible light

Three halogen-containing pyridine carboxylic acid ligands (6-fluoropicolinic acid, 6-chloropicolinic acid, and 6-bromopicolinic acid) were combined with nickel to form three types of complexes: Ni-O ((6,6′-oxydipicoline acid) Ni(H2O)2), Ni-(OH)2((6,6′-hydroxydipicoline acid) Ni(H2O)2) and Ni-Br2((6,6′-bromodipicoline acid) Ni(H2O)2). Interestingly, the nickel salt reacted with 6-fluoropicolinic acid to form the ether-type complex Ni-O, with 6-chloropicolinic acid to form the hydroxy-type complex Ni-(OH)2, and with 6-bromopicolinic acid to form a Ni-Br2 complex with unchanged ligands. The Ni-O and Ni-(OH)2 complexes are novel in structure and especially the Ni-O show an excellent catalytic performance on reduction of CO2 to CO. After 12 h of irradiation, the Ni-O complexes attained a CO turnover number (TON) of 5664.3 and 86.7 % selectivity. The configurations of the complex catalysts have been demonstrated to play a major role in photocatalysis, by integrating analysis of high resolution mass spectrometry (HRMS) as well as density-functional theory (DFT). A potential proton-coupled electron transfer (PCET) mechanism of two-stage photocatalytic process is proposed.

Valence Tautomerism Induced Proton Coupled Electron Transfer:X-H Bond Oxidation with a Dinuclear Au(II) Hydroxide Complex.

We report the preparation and characterization of the dinuclear AuII hydroxide complex AuII 2(L)2(OH)2 (L=N,N'-bis (2,6-dimethyl) phenylformamidinate) and study its reactivity towards weak X-H bonds. Through the interplay of kinetic analysis and computational studies, we demonstrate that the oxidation of cyclohexadiene follows a concerted proton-coupled electron transfer (cPCET) mechanism, a rare type of reactivity for Au complexes. We find that the Au-Au σ-bond undergoes polarization in the PCET event leading to an adjustment of oxidation levels for both Au centers prior to C(sp3)-H bond cleavage. We thus describe the oxidation event as a valence tautomerism-induced PCET where the basicity of one reduced Au-OH unit provides a proton acceptor and the second more oxidized Au center serves as an electron acceptor. The coordination of these events allows for unprecedented radical-type reactivity by a closed shell AuII complex.

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process.

Electrochemically generated amidyl radical species produced distinct inter- or intramolecular hydroamination reaction products via a proton-coupled electron transfer (PCET) mechanism. Cyclic voltammetry (CV) analysis indicated that the chemoselectivity was derived from the size of the hydrogen bond complex, which consisted of the carbamate substrate and phosphate base, and could be controlled using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as an additive. These results provide fundamental insights for the design of PCET-based redox reaction systems under electrochemical conditions.

Switching the proton-coupled electron transfer mechanism for non-canonical tyrosine residues in a de novo protein.

The proton-coupled electron transfer (PCET) reactions of tyrosine (Y) are instrumental to many redox reactions in nature. This study investigates how the local environment and the thermodynamic properties of Y influence its PCET characteristics. Herein, 2- and 4-mercaptophenol (MP) are placed in the well-folded α3C protein (forming 2MP-α3C and 4MP-α3C) and oxidized by external light-generated [Ru(L)3]3+ complexes. The resulting neutral radicals are long-lived (>100 s) with distinct optical and EPR spectra. Calculated spin-density distributions are similar to canonical Y˙ and display very little spin on the S-S bridge that ligates the MPs to C32 inside the protein. With 2MP-α3C and 4MP-α3C we probe how proton transfer (PT) affects the PCET rate constants and mechanisms by varying the degree of solvent exposure or the potential to form an internal hydrogen bond. Solution NMR ensemble structures confirmed our intended design by displaying a major difference in the phenol OH solvent accessible surface area (≤∼2% for 2MP and 30-40% for 4MP). Additionally, 2MP-C32 is within hydrogen bonding distance to a nearby glutamate (average O-O distance is 3.2 ± 0.5 Å), which is suggested also by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations. Neither increased exposure of the phenol OH to solvent (buffered water), nor the internal hydrogen bond, was found to significantly affect the PCET rates. However, the lower phenol pKa values associated with the MP-α3C proteins compared to α3Y provided a sufficient change in PT driving force to alter the PCET mechanism. The PCET mechanism for 2MP-α3C and 4MP-α3C with moderately strong oxidants was predominantly step-wise PTET for pH values, but changed to concerted PCET at neutral pH values and below when a stronger oxidant was used, as found previously for α3Y. This shows how the balance of ET and PT driving forces is critical for controlling PCET mechanisms. The presented results improve our general understanding of amino-acid based PCET in enzymes.