Proton-coupled electron transfer reactivities of electronically divergent heme superoxide intermediates: a kinetic,thermodynamic, and theoretical study

Heme superoxides are one of the most versatile metallo-intermediates in biology, and they mediate a vast variety of oxidation and oxygenation reactions involving O_2(g). Overall proton-coupled electron transfer (PCET) processes they facilitate may proceed via several different mechanistic pathways, attributes of which are not yet fully understood. Herein we present a detailed investigation into concerted PCET events of a series of geometrically similar, but electronically disparate synthetic heme superoxide mimics, where unprecedented, PCET feasibility-determining electronic effects of the heme center have been identified. These electronic factors firmly modulate both thermodynamic and kinetic parameters that are central to PCET, as supported by our experimental and theoretical observations. Consistently, the most electron-deficient superoxide adduct shows the strongest driving force for PCET, whereas the most electron-rich system remains unreactive. The pivotal role of these findings in understanding significant heme systems in biology, as well as in alternative energy applications is also discussed.

Electronic characteristics of heme significantly influence the feasibility of hydrogen atom abstraction by synthetic heme superoxide moieties, shedding new light on analogous scenarios implicated in both biological and alternate energy applications.     

Proton-coupled electron transfer across benzimidazole bridges in bioinspired proton wires

Designing molecular platforms for controlling proton and electron movement in artificial photosynthetic systems is crucial to efficient catalysis and solar energy conversion. The transfer of both protons and electrons during a reaction is known as proton-coupled electron transfer (PCET) and is used by nature in myriad ways to provide low overpotential pathways for redox reactions and redox leveling, as well as to generate bioenergetic proton currents. Herein, we describe theoretical and electrochemical studies of a series of bioinspired benzimidazole-phenol (BIP) derivatives and a series of dibenzimidazole-phenol (BI₂P) analogs with each series bearing the same set of terminal proton-accepting (TPA) groups. The set of TPAs spans more than 6 pK_a units. These compounds have been designed to explore the role of the bridging benzimidazole(s) in a one-electron oxidation process coupled to intramolecular proton translocation across either two (the BIP series) or three (the BI₂P series) acid/base sites. These molecular constructs feature an electrochemically active phenol connected to the TPA group through a benzimidazole-based bridge, which together with the phenol and TPA group form a covalent framework supporting a Grotthuss-type hydrogen-bonded network. Infrared spectroelectrochemistry demonstrates that upon oxidation of the phenol, protons translocate across this well-defined hydrogen-bonded network to a TPA group. The experimental data show the benzimidazole bridges are non-innocent participants in the PCET process in that the addition of each benzimidazole unit lowers the redox potential of the phenoxyl radical/phenol couple by 60 mV, regardless of the nature of the TPA group. Using a series of hypothetical thermodynamic steps, density functional theory calculations correctly predicted the dependence of the redox potential of the phenoxyl radical/phenol couple on the nature of the final protonated species and provided insight into the thermodynamic role of dibenzimidazole units in the PCET process. This information is crucial for developing molecular “dry proton wires” with these moieties, which can transfer protons via a Grotthuss-type mechanism over long distances without the intervention of water molecules.

Experimental and theoretical methods characterize the thermodynamics of electrochemically driven proton-coupled electron transfer processes in bioinspired constructs involving multiple proton translocations over Grotthus-type proton wires.     

Photoinduced Electron vs. Concerted Proton Electron Transfer Pathways in SnIV (l-Tryptophanato)2 Porphyrin Conjugates

Aromatic amino acids such as l -tyrosine and l -tryptophan are deployed in natural systems to mediate electron transfer (ET) reactions. While tyrosine oxidation is always coupled to deprotonation (proton-coupled electron-transfer, PCET), both ET-only and PCET pathways can occur in the case of the tryptophan residue. In the present work, two novel conjugates 1 and 2 , based on a Sn^IV tetraphenylporphyrin and Sn^IV octaethylporphyrin, respectively, as the chromophore/electron acceptor and l -tryptophan as electron/proton donor, have been prepared and thoroughly characterized by a combination of different techniques including single crystal X-ray analysis. The photophysical investigation of 1 and 2 in CH₂Cl₂ in the presence of pyrrolidine as a base shows that different quenching mechanisms are operating upon visible-light excitation of the porphyrin component, namely photoinduced electron transfer and concerted proton electron transfer (CPET), depending on the chromophore identity and spin multiplicity of the excited state. The results are compared with those previously described for metal-mediated analogues featuring Sn^IV porphyrin chromophores and l -tyrosine as the redox active amino acid and well illustrate the peculiar role of l -tryptophan with respect to PCET.     

Highly Polarized Coumarin Derivatives Revisited: Solvent-Controlled Competition Between Proton-Coupled Electron Transfer and Twisted Intramolecular Charge Transfer

Linking a polarized coumarin unit with an aromatic substituent via an amide bridge results in weak electronic coupling that affects the intramolecular electron-transfer (ET) process. As a result of this, interesting solvent-dependent photophysical properties can be observed. In polar solvents, electron transfer in coumarin derivatives of this type induces a mutual twist of the electron-donating and -accepting molecular units (TICT process) that facilitates radiationless decay processes (internal conversion). In the dyad with the strongest intramolecular hydrogen bond, the planar form is stabilized, such that twisting can only occur in highly polar solvents, whereas a fast proton-coupled electron-transfer (PCET process) occurs in nonpolar n-alkanes. The k_PCET rate constant decreases linearly with the energy of the fluorescence maximum in different solvents. This observation can be explained in terms of competition between electron- and proton-transfer from a highly polarized (ca. 15 D) and fluorescent locally excited (¹LE) state to a much less polarized (ca. 4 D) charge-transfer (¹CT) state, a unique occurrence. Photophysical measurements performed for a family of related coumarin dyads, together with results of quantum-chemical computations, give insight into the mechanism of the ET process, which is followed by either a TICT or a PCET process. Our results reveal that dielectric solvation of the excited state slows down the PCET process, even in nonpolar solvents.     

Solvent-modulated proton-coupled electron transfer in an iridium complex with an ESIPT ligand

Proton-coupled electron transfer (PCET), an essential process in nature with a well-known example of photosynthesis, has recently been employed in metal complexes to improve the energy conversion efficiency; however, a profound understanding of the mechanism of PCET in metal complexes is still lacking. In this study, we synthesized cyclometalated Ir complexes strategically designed to exploit the excited-state intramolecular proton transfer (ESIPT) of the ancillary ligand and studied their photoinduced PCET in both aprotic and protic solvent environments using femtosecond transient absorption spectroscopy and density functional theory (DFT) and time-dependent DFT calculations. The data reveal solvent-modulated PCET, where charge transfer follows proton transfer in an aprotic solvent and the temporal order of charge transfer and proton transfer is reversed in a protic solvent. In the former case, ESIPT from the enol form to the keto form, which precedes the charge transfer from Ir to the ESIPT ligand, improves the efficiency of metal-to-ligand charge transfer. This finding demonstrates the potential to control the PCET reaction in the desired direction and the efficiency of charge transfer by simply perturbing the external hydrogen-bonding network with the solvent.

The iridium complex with an ESIPT ligand shows solvent-modulated proton-coupled electron transfer, in which the temporal order of proton transfer and charge transfer is altered by the solvent environment.     

Synthesis of oxalamides by acceptorless dehydrogenative coupling of ethylene glycol and amines and the reverse hydrogenation catalyzed by ruthenium

A sustainable, new synthesis of oxalamides, by acceptorless dehydrogenative coupling of ethylene glycol with amines, generating H₂, homogeneously catalyzed by a ruthenium pincer complex, is presented. The reverse hydrogenation reaction is also accomplished using the same catalyst. A plausible reaction mechanism is proposed based on stoichiometric reactions, NMR studies, X-ray crystallography as well as observation of plausible intermediates.

Ruthenium catalyzed acceptorless dehydrogenative coupling of ethylene glycol and amines to oxalamides is reported. The reverse hydrogenation reaction is also accomplished.     

Hydrogen atom transfer from iron(II)-tris[2,2'-bi(tetrahydropyrimidine)] to TEMPO: a negative enthalpy of activation predicted by the Marcus equation

The transfer of a hydrogen atom from iron(II)-tris[2,2'-bi(tetrahydropyrimidine)], [FeII(H2bip)3]2+, to the stable nitroxide, TEMPO, was studied by stopped-flow UV-vis spectrophotometry. The products are the deprotonated iron(III) complex [FeIII(H2bip)2(Hbip)]2+ and the hydroxylamine, TEMPO-H. This reaction can also be referred to as proton-coupled electron transfer (PCET). The equilibrium constant for the reaction is close to 1; thus, the reaction can be driven in either direction. The rate constants for the forward and reverse reactions at 298 K are k1 = 260 +/- 30 M-1 s-1 and k-1 = 150 +/- 20 M-1 s-1. Interestingly, the rate constant for the forward reaction decreases as reaction temperature is increased, implying a negative activation enthalpy: DeltaH1 = -2.7 +/- 0.4 kcal mol-1, DeltaS1 = -57 +/- 8 cal mol-1 K-1. Marcus theory predicts this unusual temperature dependence on the basis of independently measured self-exchange rate constants and equilibrium constants: DeltaHcalcd = -3.5 +/- 0.5 kcal mol-1, DeltaScalcd = -42 +/- 10 cal mol-1 K-1. This result illustrates the value of the Marcus approach for these types of reactions. The dominant contributor to the negative activation enthalpy is the favorable enthalpy of reaction, DeltaH1 degrees = -9.4 +/- 0.6 kcal mol-1, rather than the small negative activation enthalpy for the H-atom self-exchange between the iron complexes.     

Strategies for switching the mechanism of proton-coupled electron transfer reactions illustrated by mechanistic zone diagrams

The mechanism by which proton-coupled electron transfer (PCET) occurs is of fundamental importance and has great consequences for applications, e.g. in catalysis. However, determination and tuning of the PCET mechanism is often non-trivial. Here, we apply mechanistic zone diagrams to illustrate the competition between concerted and stepwise PCET-mechanisms in the oxidation of 4-methoxyphenol by Ru(bpy)₃³⁺-derivatives in the presence of substituted pyridine bases. These diagrams show the dominating mechanism as a function of driving force for electron and proton transfer (ΔG⁰_ET and ΔG⁰_PT) respectively [Tyburski et al., J. Am. Chem. Soc., 2021, 143, 560]. Within this framework, we demonstrate strategies for mechanistic tuning, namely balancing of ΔG⁰_ET and ΔG⁰_PT, steric hindrance of the proton-transfer coordinate, and isotope substitution. Sterically hindered pyridine bases gave larger reorganization energy for concerted PCET, resulting in a shift towards a step-wise electron first-mechanism in the zone diagrams. For cases when sufficiently strong oxidants are used, substitution of protons for deuterons leads to a switch from concerted electron–proton transfer (CEPT) to an electron transfer limited (ETPT_lim) mechanism. We thereby, for the first time, provide direct experimental evidence, that the vibronic coupling strength affects the switching point between CEPT and ETPT_lim, i.e. at what driving force one or the other mechanism starts dominating. Implications for solar fuel catalysis are discussed.

The mechanism by which proton-coupled electron transfer (PCET) occurs is of fundamental importance and has great consequences for applications, e.g. in catalysis.     

Electron-transfer oxidation properties of unsaturated fatty acids and mechanistic insight into lipoxygenases

Rate constants of photoinduced electron-transfer oxidation of unsaturated fatty acids with a series of singlet excited states of oxidants in acetonitrile at 298 K were examined and the resulting electron-transfer rate constants (k(et)) were evaluated in light of the free energy relationship of electron transfer to determine the one-electron oxidation potentials (E(ox)) of unsaturated fatty acids and the intrinsic barrier of electron transfer. The k(et) values of linoleic acid with a series of oxidants are the same as the corresponding k(et) values of methyl linoleate, linolenic acid, and arachidonic acid, leading to the same E(ox) value of linoleic acid, methyl linoleate, linolenic acid, and arachidonic acid (1.76 V vs SCE), which is significantly lower than that of oleic acid (2.03 V vs SCE) as indicated by the smaller k(et) values of oleic acid than those of other unsaturated fatty acids. The radical cation of linoleic acid produced in photoinduced electron transfer from linoleic acid to the singlet excited state of 10-methylacridinium ion as well as that of 9,10-dicyanoanthracene was detected by laser flash photolysis experiments. The apparent rate constant of deprotonation of the radical cation of linoleic acid was determined as 8.1 x 10(3) s(-1). In the presence of oxygen, the addition of oxygen to the deprotonated radical produces the peroxyl radical, which has successfully been detected by ESR. No thermal electron transfer or proton-coupled electron transfer has occurred from linoleic acid to a strong one-electron oxidant, Ru(bpy)3(3+) (bpy = 2,2'-bipyridine) or Fe(bpy)3(3+). The present results on the electron-transfer and proton-transfer properties of unsaturated fatty acids provide valuable mechanistic insight into lipoxygenases to clarify the proton-coupled electron-transfer process in the catalytic function.     

Ground- and excited-state dynamic control of an anion receptor by hydrostatic pressure

Stimulus-responsive supramolecular architectures have become an attractive alternative to conventional ones for many applications in sensing, drug-delivery and switchable memory systems. Herein, we used an anion receptor (H: host) as a hydrostatic-pressure-manipulatable fluorescence foldamer and halide anions as chiral (binaphthylammonium) and achiral (tetrabutylammonium) ion pairs (SS or RR·X and TBA·X; X = Cl, Br), and then investigated their (chir)optical properties and molecular recognition behavior under hydrostatic pressures. The conformational changes and optical properties of H in various organic solvents were revealed by UV/vis absorption and fluorescence spectra and fluorescence lifetimes upon hydrostatic pressurization. The anion-recognition abilities of H upon interactions with SS or RR·X and TBA·X at different pressure ranges were determined by hydrostatic-pressure spectroscopy to quantitatively afford the binding constant (K_anion) and apparent reaction volume changes . The results obtained indicate that hydrostatic pressure as well as solvation plays significant roles in the dynamic control of the present supramolecular system in the ground and excited states. This work will provide a new guideline for further developing hydrostatic-pressure-responsive foldamers and supramolecular materials.

Hydrostatic pressure can control interactions of chiral countercations with helical receptors containing anions, causing remarkable chiroptical changes.     

One-electron oxidation of a hydrogen-bonded phenol occurs by concerted proton-coupled electron transfer

The hydrogen-bonded phenol 2-(aminodiphenylmethyl)-4,6-di-tert-butylphenol (HOAr-NH2) was prepared and oxidized in MeCN by a series of one-electron oxidants. The product is the phenoxyl radical in which the phenolic proton has transferred to the amine, *OAr-NH3+. The reaction of HOAr-NH2 and tris(p-tolyl)aminium ([N(tol)3]*+) to give *OAr-NH3+ + N(tol)3 has Keq = 2.0 +/- 0.5, follows second-order kinetics with k = (1.1 +/- 0.2) x 105 M-1 s-1 (DeltaG = 11 kcal mol-1), and has a primary isotope effect kH/kD = 2.4 +/- 0.4. Oxidation of HOAr-NH2 with [N(C6H4Br)3]*+ is faster, with k congruent with 4 x 107 M-1 s-1. The isotope effect, thermochemical arguments, and the dependence of the rate on driving force (DeltaDeltaG/DeltaDeltaG degrees = 0.53) all indicate that electron transfer from HOAr-NH2 must occur concerted with intramolecular proton transfer from the phenol to the amine (proton-coupled electron transfer, PCET). The data rule out stepwise paths that involve initial electron transfer to form the phenol radical cation *+HOAr-NH2 or that involve initial proton transfer to give the zwitterion -OAr-NH3+. The dependence of the electron-transfer rate constants on driving force can be fit with the adiabatic Marcus equation, yielding a large intrinsic barrier: lambda = 34 kcal mol-1 for reactions of HOAr-NH2 with NAr3*+.     

Insights into the Role of Graphitic Carbon Nitride as a Photobase in Proton-Coupled Electron Transfer in (sp3)C−H Oxygenation of Oxazolidinones

Graphitic carbon nitride (g-CN) is a transition metal free semiconductor that mediates a variety of photocatalytic reactions. Although photoinduced electron transfer is often postulated in the mechanism, proton-coupled electron transfer (PCET) is a more favorable pathway for substrates possessing X−H bonds. Upon excitation of an (sp²)N-rich structure of g-CN with visible light, it behaves as a photobase—it undergoes reductive quenching accompanied by abstraction of a proton from a substrate. The results of modeling allowed us to identify active sites for PCET—the ‘triangular pockets’ on the edge facets of g-CN. We employ excited state PCET from the substrate to g-CN to selectively cleavethe endo-(sp³)C−H bond in oxazolidine-2-ones followed by trapping the radical with O₂. This reaction affords 1,3-oxazolidine-2,4-diones. Measurement of the apparent pK_a value and modeling suggest that g-CN excited state can cleave X−H bonds that are characterized by bond dissociation free energy (BDFE) ≈100 kcal mol⁻¹.     

Biomimetic hydrogen-bonding cascade for chemical activation: telling a nucleophile from a base

Hydrogen bonding-assisted polarization is an effective strategy to promote bond-making and bond-breaking chemical reactions. Taking inspiration from the catalytic triad of serine protease active sites, we have devised a conformationally well-defined benzimidazole platform that can be systematically functionalized to install multiple hydrogen bonding donor (HBD) and acceptor (HBA) pairs in a serial fashion. We found that an increasing number of interdependent and mutually reinforcing HBD–HBA contacts facilitate the bond-forming reaction of a fluorescence-quenching aldehyde group with the cyanide ion, while suppressing the undesired Brønsted acid–base reaction. The most advanced system, evolved through iterative rule-finding studies, reacts rapidly and selectively with CN⁻ to produce a large (>180-fold) enhancement in the fluorescence intensity at λ_max = 450 nm.

Biomimetic cascade hydrogen bonds promote covalent capture of a nucleophile by polarizing the electrophilic reaction site, while suppressing non-productive acid–base chemistry as the competing reaction pathway.     

FREE ENERGY DEPENDENCE OF THE QUENCHING OF CHLOROPHYLL a FLUORESCENCE BY SUBSTITUTED QUINONES*

The quenching of chlorophyll a (Chl a) fluorescence hy a series of substituted benzoquinones. naphthoquinones and anthraquinones has been examined employing ethanol and acetonitrile as solvents. All quinones are good quenchers of fluorescence. There is an excellent linear relation between the Stern-Volmer quenching constants, K, and the polarographic half wave potentials (E₁₂) of the quinones, with more oxidizing quinones being better quenchers. The quenching data are consistent with the excited state half wave potential of ?1.31 eV predicted theoretically, demonstrating that the kinetically estimated value of the Chl a excited state reduction potential agrees with that expected on spectroscopic grounds. The results of quenching are not in agreement with the conventional Marcus theory of electron-transfer reactions, as there is no evidence of quenching constant. K_q. decrease vsΔG⁰ even for free energy changes nearly twice that expected for the onset of the Marcus inverted region. However, the kinetically estimated K_q values are in good agreement with the ones calculated by using the Rehm and Weller equation for fluorescence quenching by electron transfer. Our experimental results support the electron transfer mechanism of quenching proposed by Seely.     

Photoredox-catalyzed aminofluorosulfonylation of unactivated olefins

The development of efficient approaches to access sulfonyl fluorides is of great significance because of the widespread applications of these structural motifs in many areas, among which the emerging sulfur(vi) fluoride exchange (SuFEx) click chemistry is the most prominent. Here, we report the first three-component aminofluorosulfonylation of unactivated olefins by merging photoredox-catalyzed proton-coupled electron transfer (PCET) activation with radical relay processes. Various aliphatic sulfonyl fluorides featuring a privileged 5-membered heterocyclic core have been efficiently afforded under mild conditions with good functional group tolerance. The synthetic potential of the sulfonyl fluoride products has been examined by diverse transformations including SuFEx reactions and transition metal-catalyzed cross-coupling reactions. Mechanistic studies demonstrate that amidyl radicals, alkyl radicals and sulfonyl radicals are involved in this difunctionalization transformation.

A three-component aminofluorosulfonylation of unactivated alkenes has been developed by merging photocatalytic PCET with radical relay processes, affording various aliphatic sulfonyl fluorides featuring medicinally privileged heterocyclic scaffolds.     

Exploiting single-electron transfer in Lewis pairs for catalytic bond-forming reactions

A single-electron transfer (SET) between tris(pentafluorophenyl)borane (B(C₆F₅)₃) and N,N-dialkylanilines is reported, which is operative via the formation of an electron donor–acceptor (EDA) complex involving π-orbital interactions as a key intermediate under dark conditions or visible-light irradiation depending on the structure of the aniline derivatives. This inherent SET in the Lewis pairs initiates the generation of the corresponding α-aminoalkyl radicals and their additions to electron-deficient olefins, revealing the ability of B(C₆F₅)₃ to act as an effective one-electron redox catalyst.

Radical–ion pair generation from common Lewis pairs and its application to catalytic carbon–carbon bond formation.     

Broadband fluorescence reveals mechanistic differences in excited-state proton transfer to protic and aprotic solvents

Excited-state proton transfer (ESPT) to solvent is often explained according to the two-step Eigen–Weller model including a contact ion pair (CIP*) as an intermediate, but general applicability of the model has not been thoroughly examined. Furthermore, examples of the spectral identification of CIP* are scarce. Here, we report on a detailed investigation of ESPT to protic (H₂O, D₂O, MeOH and EtOH) and aprotic (DMSO) solvents utilizing a broadband fluorescence technique with sub-200 fs time resolution. The time-resolved spectra are decomposed into contributions from the protonated and deprotonated species and a clear signature of CIP* is identified in DMSO and MeOH. Interestingly, the CIP* intermediate is not observable in aqueous environment although the dynamics in all solvents are multi-exponential. Global analysis based on the Eigen–Weller model is satisfactory in all solvents, but the marked mechanistic differences between aqueous and organic solvents cast doubt on the physical validity of the rate constants obtained.

Time-resolved broadband fluorescence facilitates direct observation of reaction intermediates in excited-state proton transfer to solvent in protic and aprotic solvents.     

Direct Enamido C(sp2)−H Diphosphorylation Enabled by a PCET-Triggered Double Radical Relay: Access to gem-Bisphosphonates

Herein we report a novel and straightforward protocol for the construction of valuable gem-BPs by means of proton-coupled electron-transfer (PCET)-triggered enamido C(sp²)−H diphosphorylation. This reaction represents a rare example of realizing the challenging double C−P bond formation at a single carbon atom, thus providing facile access to a broad variety of structurally diverse bisphosphonates from simple enamides under silver-mediated conditions. Initial mechanistic studies demonstrated that the diphosphorylation involves two rounds of PCET-initiated radical relay process.     

Revealing the bonding of solvated Ru complexes with valence-to-core resonant inelastic X-ray scattering

Ru-complexes are widely studied because of their use in biological applications and photoconversion technologies. We reveal novel insights into the chemical bonding of a series of Ru(ii)- and Ru(iii)-complexes by leveraging recent advances in high-energy-resolution tender X-ray spectroscopy and theoretical calculations. We perform Ru 2p4d resonant inelastic X-ray scattering (RIXS) to probe the valence excitations in dilute solvated Ru-complexes. Combining these experiments with a newly developed theoretical approach based on time-dependent density functional theory, we assign the spectral features and quantify the metal–ligand bonding interactions. The valence-to-core RIXS features uniquely identify the metal-centered and charge transfer states and allow extracting the ligand-field splitting for all the complexes. The combined experimental and theoretical approach described here is shown to reliably characterize the ground and excited valence states of Ru complexes, and serve as a basis for future investigations of ruthenium, or other 4d metals active sites, in biological and chemical applications.

Combined experimental and theoretical Ru 2p4d resonant inelastic X-ray scattering study probes the chemical bonding and the valence excited states of solvated Ru complexes.