Proton‐Coupled Electron Transfer of Unsaturated Fatty Acids and Mechanistic Insight into Lipoxygenase

A proton‐coupled electron transfer (PCET) process plays an important role in the initial step of lipoxygenases to produce lipid radicals which can be oxygenated by reaction with O₂ to yield the hydroperoxides stereoselectively. The EPR spectroscopic detection of free lipid radicals and the oxygenated radicals (peroxyl radicals) together with the analysis of the EPR spectra has revealed the origin of the stereo‐ and regiochemistry of the reaction between O₂ and linoleyl (= (2Z)‐10‐carboxy‐1‐[(1Z)‐hept‐1‐enyl]dec‐2‐enyl) radical in lipoxygenases. The direct determination of the absolute rates of H‐atom‐transfer reactions from a series of unsaturated fatty acids to the cumylperoxyl (= (1‐methyl‐1‐phenylethyl)dioxy) radical by use of time‐resolved EPR at low temperatures together with detailed kinetic investigations on both photoinduced and thermal electron‐transfer oxidation of unsaturated fatty acids provides the solid energetic basis for the postulated PCET process in lipoxygenases. A strong interaction between linoleic acid (= (9Z,12Z)‐octadeca‐9,12‐dienoic acid) and the reactive center of the lipoxygenases (Fe^III? OH) is suggested to be involved to make a PCET process to occur efficiently, when an inner‐sphere electron transfer from linoleic acid to the Fe^III state is strongly coupled with the proton transfer to the OH group.     

Mechanism for the Nonadiabatic Photooxidation of Benzene to Phenol: Orientation‐Dependent Proton‐Coupled Electron Transfer

An efficient catalytic one‐step conversion of benzene to phenol was achieved recently by selective photooxidation under mild conditions with 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ) as the photocatalyst. Herein, high‐level electronic structure calculations in the gas phase and in acetonitrile solution are reported to explore the underlying mechanism. The initially populated ¹ππ* state of DDQ can relax efficiently through a nearby dark ¹nπ* doorway state to the ³ππ* state of DDQ, which is found to be the precursor state involved in the initial intermolecular electron transfer from benzene to DDQ. The subsequent triplet‐state reaction between DDQ radical anions, benzene radical cations, and water is computed to be facile. The formed DDQH and benzene‐OH radicals can undergo T₁→S₀ intersystem crossing and concomitant proton‐coupled electron transfer (PCET) to generate the products DDQH₂ and phenol. Two of the four considered nonadiabatic pathways involve an orientation‐dependent triplet PCET process, followed by intersystem crossing to the ground state (S₀). The other two first undergo a nonadiabatic T₁→S₀ transition to produce a zwitterionic S₀ complex, followed by a barrierless proton transfer. The present theoretical study identifies novel types of nonadiabatic PCET processes and provides detailed mechanistic insight into DDQ‐catalyzed photooxidation.     

Lewis Acid Coupled Electron Transfer of Metal–Oxygen Intermediates

Redox‐inactive metal ions and Brønsted acids that function as Lewis acids play pivotal roles in modulating the redox reactivity of metal–oxygen intermediates, such as metal–oxo and metal–peroxo complexes. The mechanisms of the oxidative C?H bond cleavage of toluene derivatives, sulfoxidation of thioanisole derivatives, and epoxidation of styrene derivatives by mononuclear nonheme iron(IV)–oxo complexes in the presence of triflic acid (HOTf) and Sc(OTf)₃ have been unified as rate‐determining electron transfer coupled with binding of Lewis acids (HOTf and Sc(OTf)₃) by iron(III)–oxo complexes. All logarithms of the observed second‐order rate constants of Lewis acid‐promoted oxidative C?H bond cleavage, sulfoxidation, and epoxidation reactions of iron(IV)–oxo complexes exhibit remarkably unified correlations with the driving forces of proton‐coupled electron transfer (PCET) and metal ion‐coupled electron transfer (MCET) in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes were taken into account. The binding of HOTf and Sc(OTf)₃ to the metal–oxo moiety has been confirmed for Mn^IV–oxo complexes. The enhancement of the electron‐transfer reactivity of metal–oxo complexes by binding of Lewis acids increases with increasing the Lewis acidity of redox‐inactive metal ions. Metal ions can also bind to mononuclear nonheme iron(III)–peroxo complexes, resulting in acceleration of the electron‐transfer reduction but deceleration of the electron‐transfer oxidation. Such a control on the reactivity of metal–oxygen intermediates by binding of Lewis acids provides valuable insight into the role of Ca²⁺ in the oxidation of water to dioxygen by the oxygen‐evolving complex in photosystem II.     

Distance Dependence of Bidirectional Concerted Proton–Electron Transfer in Phenol‐Ru(2,2′‐bipyridine)32+ Dyads

Proton‐coupled electron transfer (PCET) was investigated in three covalent donor–bridge–acceptor molecules with different bridge lengths. Upon photoexcitation of their Ru(bpy)₃²⁺ (bpy=2,2′‐bipyridine) photosensitizer in acetonitrile, intramolecular long‐range electron transfer from a phenolic unit to Ru(bpy)₃²⁺ occurs in concert with release of the phenolic proton to pyrrolidine base. The kinetics of this bidirectional concerted proton–electron transfer (CPET) reaction were studied as a function of phenol–Ru(bpy)₃²⁺ distance by increasing the number of bridging p‐xylene units. A distance decay constant (β) of 0.67±0.23 Å^?1 was determined. The distance dependence of the rates for CPET is thus not significantly steeper than that for ordinary (i.e., not proton coupled) electron transfer across the same bridges, despite the concerted motion of oppositely charged particles into different directions. Long‐range bidirectional CPET is an important reaction in many proteins and plays a key role in photosynthesis; our results are relevant in the context of photoinduced separation of protons and electrons as a means of light‐to‐chemical energy conversion. This is the first determination of β for a bidirectional CPET reaction.     

Proton-Coupled Electron Transfer (PCET) with 1,4-Bisguanidino-Benzene Derivatives: Comparative Study and Use in Acid-Initiated C-H Activation

Proton-coupled electron transfer (PCET) is of key importance in modern synthetic chemistry. Redox-active guanidines were established by our group as valuable alternatives to toxic high-potential benzoquinones in a variety of different PCET reactions. In this work, the PCET reactivity of a series of 1,4-bisguanidino-benzenes varying in their redox potentials and proton affinities is evaluated. The relevant redox and protonation states are fully characterized, and the compounds sorted with respect to their PCET reactivity by comparative PCET experiments supplemented by quantum-chemical calculations. Depending on the studied reactions, the driving force is either electron transfer or proton transfer; thereby the influence of both processes on the overall reactivity could be assessed. Then, two of the PCET reagents are applied in representative oxidative aryl-aryl coupling reactions, namely the intramolecular coupling of 3,3’’-4,4’’-tetramethoxy-o-terphenyl to give the corresponding triphenylene, the intermolecular coupling of N-ethylcarbazole to give N,N’-diethyl-3,3’-bicarbazole, and in the oxidative lactonization of 2-[(4-methoxyphenyl)methyl]-benzoic acid. Under mild conditions, the reactions proceed fast and efficient. Only small amounts of acid are needed, in clear contrast to the corresponding coupling reactions with traditional high-potential benzoquinones such as DDQ or chloranil requiring a large excess of a strong acid.     

Protonation and Proton‐Coupled Electron Transfer at S‐Ligated [4Fe‐4S] Clusters

Biological [Fe‐S] clusters are increasingly recognized to undergo proton‐coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate‐ligated [4Fe‐4S] cluster [Fe₄S₄(SAr)₄]^2? ( 1 , SAr=S‐2,4‐6‐(iPr)₃C₆H₂) leads to thiol dissociation, reversibly forming [Fe₄S₄(SAr)₃L]^1? ( 2 ) and ArSH (L=solvent, and/or conjugate base). Solutions of 2 +ArSH react with the nitroxyl radical TEMPO to give [Fe₄S₄(SAr)₄]^1? ( 1_ox ) and TEMPOH. This reaction involves PCET coupled to thiolate association and may proceed via the unobserved protonated cluster [Fe₄S₄(SAr)₃(HSAr)]^1? ( 1‐H ). Similar reactions with this and related clusters proceed comparably. An understanding of the PCET thermochemistry of this cluster system has been developed, encompassing three different redox levels and two protonation states.     

Release of Formic Acid from Copper Formate: Hydride,Proton-Coupled Electron and Hydrogen Atom Transfer All Play their Role

Although the mechanism for the transformation of carbon dioxide to formate with copper hydride is well understood, it is not clear how formic acid is ultimately released. Herein, we show how formic acid is formed in the decomposition of the copper formate clusters Cu(II)(HCOO)₃⁻ and Cu(II)₂(HCOO)₅⁻. Infrared irradiation resonant with the antisymmetric C−O stretching mode activates the cluster, resulting in the release of formic acid and carbon dioxide. For the binary cluster, electronic structure calculations indicate that CO₂ is eliminated first, through hydride transfer from formate to copper. Formic acid is released via proton-coupled electron transfer (PCET) to a second formate ligand, evidenced by close to zero partial charge and spin density at the hydrogen atom in the transition state. Concomitantly, the two copper centers are reduced from Cu(II) to Cu(I). Depending on the detailed situation, either PCET or hydrogen atom transfer (HAT) takes place.     

Tuning Excited‐State Reactivity by Proton‐Coupled Electron Transfer

The reactivity, and even reaction pathway, of excited states can be tuned by proton‐coupled electron transfer (PCET). The triplet state of benzophenone functionalized with a Brønsted acid (³*BP‐COOH) showed a more powerful oxidation capability over the simple triplet state of benzophenone (³*BP). ³*BP‐COOH could remove an electron from benzene at the rate of 8.0×10⁵ m ^?1 s^?1, in contrast to the reactivity of ³*BP which was inactive towards benzene oxidation. The origin of this great enhancement on the ability of the excited states to remove electrons from substrates is attributed to the intramolecular Brønsted acid, which enables the reductive quenching of ³*BP by concerted electron–proton transfer.     

Proton‐Coupled Electron Transfer Reactions Catalysed by 3 d Metal Complexes

Proton‐coupled electron transfer (PCET) reactions are essential for a wide range of natural energy‐conversion reactions and recently, the impact of PCET pathways has been exploited in artificial systems, too. The Minireview highlights PCET reactions catalysed by first‐row transition‐metal complexes, with a focus on the water oxidation, the oxygen reduction, the hydrogen evolution, and the CO₂ reduction reaction. Special attention will be paid to systems in which the impact of such pathways is deduced by comparison to systems with “electron‐only”‐transfer pathways.     

Aligning Electronic and Protonic Energy Levels of Proton‐Coupled Electron Transfer in Water Oxidation on Aqueous TiO2

The high overpotential in water oxidation on anodes is a limiting factor for the large‐scale application of photoelectrochemical cells. To overcome this limitation, it is essential to understand the four proton‐coupled electron transfer (PCET) steps in the reaction mechanism and their implications to the overpotential. Herein, a simple scheme to compute the energies of the PCET steps in water oxidation on the aqueous TiO₂ surface using a hybrid density functional is described. An energy level diagram for fully decoupled electron‐ and proton‐transfer reactions in which both electronic and protonic levels are placed on the same potential scale is also described. The level diagram helps to visualize the electronic and protonic components of the overpotential, and points out what are needed to improve. For TiO₂, it is found that its catalytic activity is due to aligning the protonic energy levels in the PCET steps, while improving the activity requires also aligning the electronic levels.     

SnIV Porphyrin Scaffolds for Axially Bonded Multiporphyrin Arrays: Synthesis and Structure Elucidation by NMR Studies

A simple, one‐step, supramolecular strategy was adopted to synthesize Sn^IV‐porphyrin‐based axially bonded triads and higher oligomers by using meso‐pyridyl Sn^IV porphyrin, meso‐hydroxyphenyl‐21,23‐dithiaporphyrin, and Ru^II porphyrin as building blocks and employing complementary and non‐interfering Sn^IV?O and Ru^II ??? N interactions. The multiporphyrin arrays are stable and robust and were purified by column chromatography. ¹H, ¹H–¹H COSY and NOESY NMR spectroscopic studies were used to unequivocally deduce the molecular structures of Sn^IV‐porphyrin‐based triads and higher oligomers. Absorption and electrochemical studies indicated weak interaction among the different porphyrin units in triads and higher oligomers, in support of the supramolecular nature of the arrays. Steady‐state fluorescence studies on triads indicated the possibility of energy transfer in the singlet state from the basal Sn^IV porphyrin to the axial 21,23‐dithiaporphyrin. However, the higher oligomers were weakly fluorescent due to the presence of heavy Ru^II porphyrin unit(s), which quench the fluorescence of the Sn^IV porphyrin and 21,23‐dithiaporphyrin units.     

Evidence for a Proton-Coupled Electron Transfer Mechanism in a Biomimetic System for Monoamine Oxidase B Catalysis

Mechanistic studies with 5-ethyl-3-methyllumiflavinium (Fl⁺) perchlorate, a biomimetic model for flavoenzyme monoamine oxidase B (MAO-B) catalysis, and the tertiary, allyl amine 1-methyl-4-(1-methyl-1 H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (MMTP) reveal that proton-coupled electron transfer (PCET) may be an important pathway for MAO catalysis. The first step involves a single-electron transfer (SET) leading to the free radicals Fl^. and MMTP^., the latter produced by deprotonation of the initially formed and highly acidic MMTP^.+. Molecular oxygen (O₂) is found to play a hitherto unrecognized role in the early steps of the oxidation. MMTP and several structurally similar tertiary amines are the only tertiary amines oxidized by MAO, and their structural/electronic properties provide the key to understanding this behavior. A general hypothesis about the role of SET in MAO catalysis, and the recognition that PCET occurs with appropriately substituted substrates is presented.     

Electron Transfer in Peptides with Cysteine and Methionine as Relay Amino Acids

Caught on the hop : In multistep electron transfer (ET) reactions through peptides, aliphatic amino acids can also act as relay stations. With cysteine, the reaction occurs as a proton‐coupled electron transfer (PCET) with water used as a mediator for the proton transfer (see picture).

     

Selective Formation of an FeIVO or an FeIIIOOH Intermediate From Iron(II) and H2O2: Controlled Heterolytic versus Homolytic Oxygen–Oxygen Bond Cleavage by the Second Coordination Sphere

We demonstrate that the devised incorporation of an alkylamine group into the second coordination sphere of an Fe^II complex allows to switch its reactivity with H₂O₂ from the usual formation of Fe^III species towards the selective generation of an Fe^IV‐oxo intermediate. The Fe^IV‐oxo species was characterized by UV/Vis absorption and Mössbauer spectroscopy. Variable‐temperature kinetic analyses point towards a mechanism in which the heterolytic cleavage of the O?O bond is triggered by a proton transfer from the proximal to the distal oxygen atom in the Fe^II‐H₂O₂ complex with the assistance of the pendant amine. DFT studies reveal that this heterolytic cleavage is actually initiated by an homolytic O?O cleavage immediately followed by a proton‐coupled electron transfer (PCET) that leads to the formation of the Fe^IV‐oxo and release of water through a concerted mechanism.     

卟啉-噁二唑二元体系光诱导能量及电子传递研究

以5-对氨基苯基-10,15,20-三苯基卟啉及2-苯基-5-(对氨基苯基)-1,3,4-噁二唑为原料合成了系列卟啉-噁二唑二元化合物, 其结构通过¹H NMR, ESI-MS, IR, UV-Vis确定. 对合成化合物进行光谱性能测定, 结果表明, 在卟啉与噁二唑混合体系中, 存在着卟啉激发态分子向噁二唑基态分子的分子间电子传递过程, 导致卟啉激发态的荧光猝灭; 在卟啉-噁二唑二元体系中, 315 nm激发下发生了由激发态噁二唑基团至卟啉基团的能量传递, 导致噁二唑基团荧光猝灭, 卟啉基团荧光增强. 420 nm激发下不存在分子内卟啉基团向噁二唑基团的电子回传竞争; 电化学性能测定进一步表明从噁二唑基团向卟啉基团的电子传递是可能的. 因此卟啉-噁二唑二元化合物可能作为一种模型, 模拟光合作用中电子给体至叶绿素之间的电子传递过程.     

Water Molecules Gating a Photoinduced One‐Electron Two‐Protons Transfer in a Tyrosine/Histidine (Tyr/His) Model of Photosystem II

We investigate a biomimetic model of a Tyr_Z/His₁₉₀ pair, a hydrogen‐bonded phenol/imidazole covalently attached to a porphyrin sensitizer. Laser flash photolysis in the presence of an external electron acceptor reveals the need for water molecules to unlock the light‐induced oxidation of the phenol through an intramolecular pathway. Kinetics monitoring encompasses two fast phases with distinct spectral properties. The first phase is related to a one‐electron transfer from the phenol to the porphyrin radical cation coupled with a domino two‐proton transfer leading to the ejection of a proton from the imidazole–phenol pair. The second phase concerns conveying the released proton to the porphyrin N₄ coordinating cavity. Our study provides an unprecedented example of a light‐induced electron‐transfer process in a Tyr_Z/His₁₉₀ model of photosystem II, evidencing the movement of both the phenol and imidazole protons along an isoenergetic pathway.     

Hydrocarbon Oxidation by a Porphyrin-π-Cation Radical Complex

Heme and chlorin π-cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π-cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a Ni^II-porphyrin-π-cation complex ([Ni^II(P⋅⁺)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([Ni^II(P⋅⁺)]) working in concert with atmospheric O₂ to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin-π-cation radical species oxidised substrates through a concerted PCET mechanism, where the porphyrin-π-cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π-cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non-innocence could be a readily manipulated resource for oxidation catalyst development.     

High‐Affinity Proton Donors Promote Proton‐Coupled Electron Transfer by Samarium Diiodide

The relationship between proton‐donor affinity for Sm^II ions and the reduction of two substrates (anthracene and benzyl chloride) was examined. A combination of spectroscopic, thermochemical, and kinetic studies show that only those proton donors that coordinate or chelate strongly to Sm^II promote anthracene reduction through a PCET process. These studies demonstrate that the combination of Sm^II ions and water does not provide a unique reagent system for formal hydrogen atom transfer to substrates.     

Density Functional Studies on Isomerization of Prostaglandin H2 to Prostacyclin Catalyzed by Cytochrome P450

At the double : DFT studies on the biosynthesis of prostacyclin (PGI₂, see scheme) from prostaglandin H₂ (PGH₂) show two reaction mechanisms through two different oxidation states, an Fe^IV–porphyrin intermediate and an Fe^III–porphyrin π‐cation radical, followed by a proton‐coupled electron‐transfer process.

     

Unusual Photoinduced Electron Transfer from a Zinc Porphyrin to a Tetrapyridyl Free‐Base Porphyrin in a Noncovalent Multiporphyrin Array

Excitation of the peripheral Zn porphyrin units in a noncovalent five‐porphyrin array, formed by gable‐like zinc(II) bisporphyrins and a central free‐base meso‐tetrakis(4‐pyridyl)porphyrin in a 2:1 ratio, ( ZnP₂ )₂? ( TPyP ), does not lead to a quantitative sensitization of the luminescence of the free‐base porphyrin acceptor, even though there is an effective energy transfer. Time resolution of the luminescence evidences a quenching of TPyP upon sensitization by the peripheral ZnP₂ . The time evolution of the TPyP fluorescence in the complex can be described by a bi‐exponential fitting with a major component of 180 ps and a minor one of 5 ns, compared to an isolated TPyP lifetime of 9.4 ns. The two quenched lifetimes are shown to be correlated to the presence of 2:1 and 1:1 complexes, respectively. No quenching of TPyP fluorescence occurs in ( ZnP₂ )₂?( TPyP ) at 77 K in a rigid solvent for which only an energy‐transfer process (τ=150±10 ps) from peripheral ZnP₂ to the central TPyP is observed. An unusual HOMO–HOMO electron‐transfer reaction from ZnP₂ to the excited TPyP units, responsible for the observed phenomena, is detected. The resulting charge‐separated state, ( ZnP₂ )⁺₂?( TPyP )^? is found to recombine to the ground state with a lifetime of 11 ns.