Proton-coupled Electron Transfer Research Articles

Synthesis of 2‐Quinolones based on Visible Light‐Catalyzed Annulation of Diazo compounds

AbstractHerein, we report a photocatalytic method for the synthesis of 2‐quinolones under mild conditions by employing α‐diazo acetamide as substrates. The use of Eosin Y as a photocatalyst allows an economical and environmentally benign synthetic method. The process involves the generation of radicals from diazo compounds promoted by a visible‐light‐induced proton‐coupled electron transfer (PCET) mechanism. The method demonstrates a broad substrate scope to provide various aryl‐ and alkyl‐substituted 2‐quinolones. To support the proposed mechanism, a series of mechanistic experiments were conducted.

Elementary Reactions in the Functional Triads of the Blue-Light Photoreceptor BLUF Domain.

The blue light using the flavin (BLUF) domain is one of the smallest photoreceptors in nature, which consists of a unique bidirectional electron-coupled proton relay process in its photoactivation reaction cycle. This perspective summarizes our recent efforts in dissecting the photocycle into three elementary processes, including proton-coupled electron transfer (PCET), proton rocking, and proton relay. Using ultrafast spectroscopy, we have determined the temporal sequence, rates, kinetic isotope effects (KIEs), and concertedness of these elementary steps. Our findings provide important implications for illuminating the photoactivation mechanism of the BLUF domain and suggest an engineering platform to characterize intricate reactions involving proton motions that are ubiquitous in nonphotosensitive protein machines.

Matched Redox Kinetics on Triazine-Based Carbon Nitride/Ni(OH)2 for Stoichiometric Overall Photocatalytic CO2 Conversion.

Mismatched reaction kinetics of CO2 reduction and H2O oxidation is the main obstacle limiting the overall photocatalytic CO2 conversion. Here, a molten salt strategy is used to construct tubular triazine-based carbon nitride (TCN) with more adsorption sites and stronger activation capability. Ni(OH)2 nanosheets are then grown over the TCN to trigger a proton-coupled electron transfer for a stoichiometric overall photocatalytic CO2 conversion via "3CO2 + 2H2O = CH4 + 2CO + 3O2." TCN reduces the energy barrier of H2O dissociation to promote H2O oxidation to O2 and supply sufficient protons to Ni(OH)2, whereby the CO2 conversion is accelerated due to the enhanced proton-coupled electron transfer process enabled by the sufficient proton supply from TCN. This work highlights the importance of matching the reaction kinetics of CO2 reduction and H2O oxidation by proton-coupled electron transfer on stoichiometric overall photocatalytic CO2 conversion.

Divergent Electrochemical Synthesis of Indoles through pKa Regulation of Amides: Synthetic and Mechanistic Insights.

A divergent synthetic approach to access highly substituted indole scaffolds is illustrated. By virtue of a tunable electrochemical strategy, distinct control over the C-3 substitution pattern was achieved by employing two analogous 2-styrylaniline precursors. The chemoselectivity is governed by the fine-tuning of the acidity of the amide proton, relying on the appropriate selection of N-protecting groups, and assisted by the reactivity of the electrogenerated intermediates. Detailed mechanistic investigations based on cyclic voltametric experiments and computational studies revealed the crucial role of water additive, which assists the proton-coupled electron transfer event for highly acidic amide precursors, followed by an energetically favorable intramolecular C-N coupling, causing exclusive fabrication of the C-3 unsubstituted indoles. Alternatively, the implementation of an electrogenerated cationic olefin activator delivers the C-3 substituted indoles through the preferential nucleophilic nature of the N-acyl amides. This electrochemical approach of judicious selection of N-protecting groups to regulate pKa/E° provides an expansion in the domain of switchable generation of heterocyclic derivatives in a sustainable fashion, with high regio- and chemoselectivity.

Incorporation of Ruthenium Ions into Nanometer-Thick Films of Copper Sulfide by Anodization for Proton-Coupled Electron Transfer Reactions

Incorporation of Ruthenium Ions into Nanometer-Thick Films of Copper Sulfide by Anodization for Proton-Coupled Electron Transfer Reactions

Coordination-induced O-H/N-H bond weakening by a redox non-innocent, aluminum-containing radical

Several renewable energy schemes aim to use the chemical bonds in abundant molecules like water and ammonia as energy reservoirs. Because the O-H and N-H bonds are quite strong (>100 kcal/mol), it is necessary to identify substances that dramatically weaken these bonds to facilitate proton-coupled electron transfer processes required for energy conversion. Usually this is accomplished through coordination-induced bond weakening by redox-active metals. However, coordination-induced bond weakening is difficult with earth’s most abundant metal, aluminum, because of its redox inertness under mild conditions. Here, we report a system that uses aluminum with a redox non-innocent ligand to achieve significant levels of coordination-induced bond weakening of O-H and N-H bonds. The multisite proton-coupled electron transfer manifold described here points to redox non-innocent ligands as a design element to open coordination-induced bond weakening chemistry to more elements in the periodic table.

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.

Photocatalytic Synthesis of Indanone, Pyrone, and Pyridinone Derivatives with Diazo Compounds as Radical Precursors.

We disclose herein a photocatalytic radical cascade cyclization of diazoalkanes for the divergent synthesis of important carbocycles and heterocycles. Under the optimal reaction conditions, various indanone, pyrone, and pyridinone derivatives can be obtained in moderate to good yields. Mechanistic experiments support the formation of carbon-centered radicals from diazoalkanes through the proton-coupled electron transfer process. Scale-up reaction using continuous flow technology and useful downstream application of the formed heterocycles further render the strategy attractive and valuable.

Photocatalytic Conversion of Lignin Models into Functionalized Aromatic Molecules Initiated by the Proton-Coupled Electron Transfer Process.

A mild and efficient method for lignin β-O-4 cleavage and functionalization was achieved via photocatalysis. This protocol exhibits a broad scope of lignin models and excellent compatibility of functionalization reagents, constructing a series of functionalized lignin-based aromatic compounds. Highly selective formation of alkyl radical species through a proton-coupled electron transfer and β-scission process provides the opportunity to form new C-C and C-N bonds by reaction with electrophilic reagents.

Probing Nonadiabaticity of Proton-Coupled Electron Transfer in Ribonucleotide Reductase.

The enzyme ribonucleotide reductase, which is essential for DNA synthesis, initiates the conversion of ribonucleotides to deoxyribonucleotides via radical transfer over a 32 Å pathway composed of proton-coupled electron transfer (PCET) reactions. Previously, the first three PCET reactions in the α subunit were investigated with hybrid quantum mechanical/molecular mechanical (QM/MM) free energy simulations. Herein, the fourth PCET reaction in this subunit between C439 and guanosine diphosphate (GDP) is simulated and found to be slightly exoergic with a relatively high free energy barrier. To further elucidate the mechanisms of all four PCET reactions, we analyzed the vibronic and electron-proton nonadiabaticities. This analysis suggests that interfacial PCET between Y356 and Y731 is vibronically and electronically nonadiabatic, whereas PCET between Y731 and Y730 and between C439 and GDP is fully adiabatic and PCET between Y730 and C439 is in the intermediate regime. These insights provide guidance for selecting suitable rate constant expressions for these PCET reactions.

Synthesis, Characterization, and Reactivity of a Highly Oxidative Mononuclear Manganese(IV)-Bis(Fluoro) Complex.

Recently, transition-metal terminal nonoxo complexes have shown a remarkable ability to activate and functionalize C-H bonds via proton-coupled electron transfer (PCET). Here we report the first example of a mononuclear manganese(IV) bis(fluoro) complex bearing a tetradentate pyridinophane ligand, [MnIV(TBDAP)(F)2]2+ (3), with an X-ray single crystal structure and physicochemical characterization. The manganese(IV) bis(fluoro) complex has a very high reduction potential of 1.61 V vs SCE, thereby enabling the four-electron oxidation of mesitylene to 3,5-dimethylbenzaldehyde. Kinetic studies, including the kinetic isotope effect and employment of other toluene derivatives, reveal the electron transfer (ET)-driven PCET in the C-H bond activation of mesitylene by 3. This novel metal halide intermediate would be prominently valuable for expanding transition-metal halide chemistry.

Accelerating the generation of NiOOH by in-situ surface phosphating nickel sulfide for promoting the proton-coupled electron transfer kinetics of urea electrolysis

Nickel sulfide (Ni3S2) is a highly promising electrocatalyst for urea oxidation reaction (UOR), and NiOOH formed by the surface phase transition of Ni3S2 during UOR is the ideal catalytic active species. However, the strong covalent bonds of Ni3S2 hinders the generation of NiOOH, limiting the further improvement of UOR activity. Herein, the Ni3S2@Ni3P core–shell nanorods have been constructed by an in-situ surface phosphating method to boost UOR performance, realizing high catalytic activity (100/1000 mA cm−2 at 1.36/1.49 V vs. RHE, respectively) and a rapid kinetics (19.13 mV dec-1). The Ni3P on the surface of Ni3S2 can rapidly form highly active γ-NiOOH with low energy consumption, and the formed Ni3S2@γ-NiOOH accelerates proton-coupled electron transfer (PCET) kinetics through reducing the energy barrier of urea dehydrogenation process, thereby enhancing UOR intrinsic activity. In addition, we also demonstrate a Ni3S2@Ni3P//Ni3S2@Ni3P urea electrolysis device with low voltages of 1.54 and 1.69 V at current densities of 100 and 500 mA cm−2, respectively. This work proposes an efficient strategy to accelerate the generation of NiOOH on the surface of Ni3S2 during UOR electrocatalysis, revealing the enhanced UOR mechanism of Ni3S2@Ni3P, which can promote the development of urea-assisted hydrogen production.

Steering CO2 Electroreduction to C2+ Products via Enhancing Localized *CO Coverage and Local Pressure in Conical Cavity.

The electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) involves a multistep proton-coupled electron transfer (PCET) process that generates a variety of intermediates, making it challenging to transform them into target products with high activity and selectivity. Here, a catalyst featuring a nanosheet-stacked sphere structure with numerous open and deep conical cavities (OD-CCs) is reported. Under the guidance of the finite-element method (FEM) simulations and theoretical analysis, it is shown that exerting control over the confinement space results in diffusion limitation of the carbon intermediates, thereby increasing local pressure and subsequently enhancing localized *CO coverage for dimerization. The nanocavities exhibit a structure-driven shift in selectivity of multicarbon (C2+) product from 41.8% to 81.7% during the CO2RR process.

Visible‐Light‐Photocatalyzed Pinacol Coupling in Water

AbstractWe present a green and efficient approach for synthesizing vicinal diols via a metal‐free photocatalyzed pinacol coupling reaction in water or aqueous media. The mild and practical reaction conditions, including a commercially available organic photocatalyst and a nontoxic solvent, provide wide functional group tolerance while furnishing the corresponding vicinal diols in high yields. Mechanistic studies reveal the crucial role of Hantzsch ester (HEH), which undergoes single‐electron oxidation and subsequently acts as a proton donor to aldehydes for proton‐coupled electron transfer (PCET). This work contributes to the development of environmentally friendly methodologies for carbon−carbon bond formation, aligning with the principles of green and sustainable chemistry.

Tip-like Fe-N4 Sites Induced Surface Microenvironments Regulation Boosts the Oxygen Reduction Reaction.

Single atom catalysts with defined local structures and favorable surface microenvironments are significant for overcoming slow kinetics and accelerating O2 electroreduction. Here, enriched tip-like FeN4 sites (T-Fe SAC) on spherical carbon surfaces were developed to investigate the change in surface microenvironments and catalysis behavior. Finite element method (FEM) simulations, together with experiments, indicate the strong local electric field of the tip-like FeN4 and the more denser interfacial water layer, thereby enhancing the kinetics of the proton-coupled electron transfer process. In situ spectroelectrochemical studies and the density functional theory (DFT) calculation results indicate the pathway transition on the tip-like FeN4 sites, promoting the dissociation of O-O bond via side-on adsorption model. The adsorbed OH* can be facilely released on the curved surface and accelerate the oxygen reduction reaction (ORR) kinetics. The obtained T-Fe SAC nanoreactor exhibits excellent ORR activities (E1/2 =0.91 V vs. RHE) and remarkable stability, exceeding those of flat FeN4 and Pt/C. This work clarified the in-depth insights into the origin of catalytic activity of tip-like FeN4 sites and held great promise in industrial catalysis, electrochemical energy storage, and many other fields.

Crystal Phase Engineering of Ultrathin Alloy Nanostructures for Highly Efficient Electroreduction of Nitrate to Ammonia.

Electrocatalytic nitrate reduction reaction (NO3RR) toward ammonia synthesis is recognized as a sustainable strategy to balance the global nitrogen cycle. However, it still remains a great challenge to achieve highly efficient ammonia production due to the complex proton-coupled electron transfer process in NO3RR. Here, the controlled synthesis of RuMo alloy nanoflowers (NFs) with unconventional face-centered cubic (fcc) phase and hexagonal close-packed/fcc heterophase for highly efficient NO3RR is reported. Significantly, fcc RuMo NFs demonstrate high Faradaic efficiency of 95.2% and a large yield rate of 32.7mg h-1 mgcat -1 toward ammonia production at 0 and -0.1V (vs reversible hydrogen electrode), respectively. In situ characterizations and theoretical calculations have unraveled that fcc RuMo NFs possess the highest d-band center with superior electroactivity, which originates from the strong Ru─Mo interactions and the high intrinsic activity of the unconventional fcc phase. The optimal electronic structures of fcc RuMo NFs supply strong adsorption of key intermediates with suppression of the competitive hydrogen evolution, which further determines the remarkable NO3RR performance. The successful demonstration of high-performance zinc-nitrate batteries with fcc RuMo NFs suggests their substantial application potential in electrochemical energy supply systems.

Origin of the multi-phasic quenching dynamics in the BLUF domains across the species

Blue light using flavin (BLUF) photoreceptors respond to light via one of nature’s smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial. Here, we incorporate site-specific fluorinated Trp into three BLUF proteins, i.e., AppA, OaPAC and SyPixD, and characterize the percentages for the Wout, WinNHin and WinNHout conformations using 19F nuclear magnetic resonance spectroscopy. Using femtosecond spectroscopy, we identify that one key WinNHin conformation can introduce a branching one-step proton transfer in AppA and a two-step proton transfer in OaPAC and SyPixD. Correlating the flavin quenching dynamics with the active-site structural heterogeneity, we conclude that the quenching rate is determined by the percentage of WinNHin, which encodes a Tyr-Gln configuration that is not conducive to proton transfer.

Heterometal Dopant Changes the Mechanism of Proton-Coupled Electron Transfer at the Polyoxovanadate-Alkoxide Surface.

The transfer of two H-atom equivalents to the titanium-doped polyoxovanadate-alkoxide, [TiV5O6(OCH3)13], results in the formation of a V(III)-OH2 site at the surface of the assembly. Incorporation of the group (IV) metal ion results in a weakening of the O-H bonds of [TiV5O5(OH2)(OCH3)13] in comparison to its homometallic congener, [V6O6(OH2)(OCH3)12], resembling more closely the thermodynamics reported for the one-electron reduced derivative, [V6O6(OH2)(OCH3)12]1-. An analysis of early time points of the reaction of [TiV5O6(OCH3)13] and 5,10-dihydrophenazine reveals the formation of an oxidized substrate, suggesting that proton-coupled electron transfer proceeds via initial electron transfer from substrate to cluster prior to proton transfer. These results demonstrate the profound influence of heterometal dopants on the mechanism of PCET with respect to the surface of the assembly.

Class Ib Ribonucleotide Reductases: Activation of a Peroxido-MnIIMnIII to Generate a Reactive Oxo-MnIIIMnIV Oxidant.

In the postulated catalytic cycle of class Ib Mn2 ribonucleotide reductases (RNRs), a MnII2 core is suggested to react with superoxide (O2·-) to generate peroxido-MnIIMnIII and oxo-MnIIIMnIV entities prior to proton-coupled electron transfer (PCET) oxidation of tyrosine. There is limited experimental support for this mechanism. We demonstrate that [MnII2(BPMP)(OAc)2](ClO4) (1, HBPMP = 2,6-bis[(bis(2 pyridylmethyl)amino)methyl]-4-methylphenol) was converted to peroxido-MnIIMnIII (2) in the presence of superoxide anion that converted to (μ-O)(μ-OH)MnIIIMnIV (3) via the addition of an H+-donor (p-TsOH) or (μ-O)2MnIIIMnIV (4) upon warming to room temperature. The physical properties of 3 and 4 were probed using UV-vis, EPR, X-ray absorption, and IR spectroscopies and mass spectrometry. Compounds 3 and 4 were capable of phenol oxidation to yield a phenoxyl radical via a concerted PCET oxidation, supporting the proposed mechanism of tyrosyl radical cofactor generation in RNRs. The synthetic models demonstrate that the postulated O2/Mn2/tyrosine activation mechanism in class Ib Mn2 RNRs is plausible and provides spectral insights into intermediates currently elusive in the native enzyme.

Core-Shell Structured Nanozyme with PDA-Mediated Enhanced Antioxidant Efficiency to Treat Early Intervertebral Disc Degeneration.

Early intervention during intervertebral disc degeneration (IDD) plays a vital role in inhibiting its deterioration and activating the regenerative process. Aiming at the high oxidative stress (OS) in the IDD microenvironment, a core-shell structured nanozyme composed of Co-doped NiO nanoparticle (CNO) as the core encapsulated with a polydopamine (PDA) shell, named PDA@CNO, was constructed, hoping to regulate the pathological environment. The results indicated that the coexistence of abundant Ni3+/Ni2+and Co3+/Co2+redox couples in CNO provided rich catalytic sites; meanwhile, the quinone and catechol groups in the PDA shell could enable the proton-coupled electron transfer, thus endowing the PDA@CNO nanozyme with multiple antioxidative enzyme-like activities to scavenge •O2-, H2O2, and •OH efficiently. Under OS conditions in vitro, PDA@CNO could effectively reduce the intracellular ROS in nucleus pulposus (NP) into friendly H2O and O2, to protect NP cells from stagnant proliferation, abnormal metabolism (senescence, mitochondria dysfunction, and impaired redox homeostasis), and inflammation, thereby reconstructing the extracellular matrix (ECM) homeostasis. The in vivo local injection experiments further proved the desirable therapeutic effects of the PDA@CNO nanozyme in a rat IDD model, suggesting great potential in prohibiting IDD from deterioration.