Roles of radical characters of pristine and nitrogen-substituted hydrographene in dioxygen bindings

We investigate by means of density functional theory (DFT) calculations how hydrogen-terminated graphenes (hydrographenes) with and without nitrogen impurities interact with dioxygen. The current study aims at searching whether hydrographenes can be utilized as cathode catalysts in fuel cell with a focus on dioxygen binding, the first step in oxygen reduction reaction (ORR). If hydrographenes have a nanometer-size rhombic structure with zigzag edges, unpaired electrons are localized at their edges with or without the nitrogen impurities. Spin localization comes from frontier orbitals of the nanometer-size hydrographenes whose amplitudes appear only at their edges. Due to their radical characters, dioxygen can bind to an edge carbon atom of the hydrographenes under the condition where fuel cell is usually operated. There are two types of dioxygen binding into a hydrographene: one is a Pauling fashion where one C-O bond is formed and the other is a bridging fashion with two formed C-O bonds. In the bridging fashion, the formation of the two C-O bonds activates dioxygen, and then radical characters of the oxygen atoms completely disappear. In contrast, the Pauling fashions retain an unpaired electron on the oxygen atom that does not participate to the C-O bond formation. The existence of radical oxygen atoms would facilitate the next step in ORR (the initial proton transfer to an adsorbed dioxygen), whereas such facilitative effects cannot be seen in its absence. According to DFT calculations, the Pauling-type bindings are always energetically preferred over the bridging-type bindings. In particular, the C→N substitution enhances the preferences of the Pauling-type binding over the bridging-type binding compared with the pristine case. Accordingly DFT calculations demonstrate that radical characters of edge carbons of a nanometer-sized rhombic hydrographene play a crucial role in dioxygen bindings in a Pauling fashion that would be responsible for enhancing the catalytic activity in fuel cell.     

Covalent Grafting of Carbon Nanotubes with a Biomimetic Heme Model Compound To Enhance Oxygen Reduction Reactions

The oxygen reduction reaction (ORR) is one of the most important reactions in both life processes and energy conversion systems. The replacement of noble‐metal Pt‐based ORR electrocatalysts by nonprecious‐metal catalysts is crucial for the large‐scale commercialization of automotive fuel cells. Inspired by the mechanisms of dioxygen activation by metalloenzymes, herein we report a structurally well‐defined, bio‐inspired ORR catalyst that consists of a biomimetic model compound—an axial imidazole‐coordinated porphyrin—covalently attached to multiwalled carbon nanotubes. Without pyrolysis, this bio‐inspired electrocatalyst demonstrates superior ORR activity and stability compared to those of the state‐of‐the‐art Pt/C catalyst in both acidic and alkaline solutions, thus making it a promising alternative as an ORR electrocatalyst for application in fuel‐cell technology.     

Transient pockets as mediators of gas molecules routes inside proteins: The case study of dioxygen pathway in homogentisate 1,2-dioxygenase and its implication in Alkaptonuria development

Alkaptonuria (AKU) is an ultra-rare disease caused by mutations in homogentisate 1,2-dioxygenase (HGD) enzyme, characterized by the loss of enzymatic activity and the accumulation of its substrate, homogentisic acid (HGA) in different tissues, leading to ochronosis and organ degeneration. Although the pathological effects of HGD mutations are largely studied, less is known about the structure of the enzyme, in particular the pathways for dioxygen diffusion to the active site, required for the enzymatic reaction, are still uninvestigated. In the present project, the combination of two in silico techniques, Molecular Dynamics (MD) simulation and Implicit Ligand Sampling (ILS), was used to delineate gas diffusion routes in HGD enzyme. A route from the central opening of the hexameric structure of the enzyme to the back of the active site trough the protein moiety was identified as the path for dioxygen diffusion, also overlapping with a transient pocket, which then assumes an important role in dioxygen diffusion. Along the route the sequence location of the missense variant E401Q, responsible for AKU development, was also found, suggesting such mutation to be conducive of enzymatic activity loss by altering the flow dynamics of dioxygen. Our in silico approach allowed also to delineate the route of HGA substrate to the active site, until now only supposed.     

In situ structural characterization of platinum dendrimer-encapsulated oxygen reduction electrocatalysts

In situ electrochemical extended X-ray absorption fine structure (EXAFS) was used to evaluate the structure of Pt dendrimer-encapsulated nanoparticles (DENs) during the oxygen reduction reaction (ORR). The DENs contained an average of just 225 atoms each. The results indicate that the Pt coordination number (CN) decreases when the electrode potential is moved to positive values. The results are interpreted in terms of an ordered core, disordered shell model. The structure of the DENs is not significantly impacted by the presence of dioxygen, but other electrogenerated species may have a significant impact on nanoparticle structure.     

碳基非贵金属氧还原电催化剂的活性位结构研究进展

以热解型Fe/N/C为代表的碳基非贵金属材料被认为是当前最具潜力替代铂的非贵金属氧还原催化剂,其综合性能的进一步突破,对于推动质子交换膜燃料电池商业化应用具有重要意义。对热解型Fe/N/C催化剂活性位结构的深入认识是实现催化剂高活性位密度和高稳定性理性设计的关键。本文总结了热解型Fe/N/C活性位的研究进展,重点介绍了非晶态铁氮配位活性中心、氮掺杂和碳缺陷三类活性位构型。由于热解型Fe/N/C是非均相的,结构非常复杂,导致在活性位认识上还存在诸多争议,本文总结阐述了活性位结构的不同观点。最后,我们展望了Fe/N/C催化剂活性位研究的未来方向。     

Evidence of Sulfur Non-Innocence in [CoII(dithiacyclam)]2+-Mediated Catalytic Oxygen Reduction Reactions

In many metalloenzymes, sulfur-containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S-ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four-nitrogen bound [Co(cyclam)]²⁺ ( 1 ; cyclam=1,5,8,11-tetraaza-cyclotetradecane) and the S-containing analog [Co(S₂N₂-cyclam)]²⁺ ( 2 ; S₂N₂-cyclam=1,8-dithia-5,11-diaza-cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere. Trapping and characterization of the intermediates formed upon dioxygen activation at the Co^II centers in 1 and 2 point to the involvement of sulfur in the O₂ reduction process as the key for the improved catalytic ORR capabilities of 2 .     

Mechanism of S-oxygenation by a cysteine dioxygenase model complex

In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, [Fe(II)(LN(3)S)](+), in which LN(3)S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O(2) was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869-3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)-superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)-oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron-oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted.     

Dioxygen Reduction in Acetonitrile with Copper Pyridylalkylamine Complexes: The Influence of Acid Strength on the Catalytic Performance

The pyridylalkylamine copper complex [Cu(tmpa)(L)]²⁺ has previously been proposed to reduce dioxygen via a dinuclear resting state, based on experiments in organic aprotic solvents using chemical reductants. Conversely, a mononuclear reaction mechanism was observed under electrochemical conditions in a neutral aqueous solution. We have investigated the electrochemical oxygen and hydrogen peroxide reduction reaction catalyzed by [Cu(tmpa)(L)]²⁺ in acetonitrile, using several different acids over a range of pK_a. We demonstrate that strong acids lead to the loss of redox reversibility and to the destabilization of the copper complex under non-catalytic conditions. Under milder conditions, the electrochemical oxygen reduction reaction (ORR) was shown to proceed via a mononuclear catalytic intermediate, similar to what we have previously observed in water. However, in acetonitrile the catalytic rate constants of the ORR are dramatically lower by a factor 10⁵, which is caused by the unfavorable equilibrium of formation of [Cu^II(O₂⋅⁻)(tmpa)]⁺ in acetonitrile. This results in higher catalytic rates for the reduction of hydrogen peroxide than for the ORR.     

Mononuclear copper(II)-hydroperoxo complex derived from reaction of copper(I) complex with dioxygen as a model of DbetaM and PHM

A mononuclear copper(II)-hydroperoxo species has been generated by the reaction of Cu(I)-H2BPPA complex with dioxygen, which illustrates the enzymatic reaction process of the CuB site in the DbetaM and PHM.     

On the Metal Cooperativity in a Dinuclear Copper–Guanidine Complex for Aliphatic C−H Bond Cleavage by Dioxygen

Selective oxidation reactions of organic compounds with dioxygen using molecular copper complexes are of relevance to synthetic chemistry as well as enzymatic reactivity. In the enzyme peptidylglycine α-hydroxylating monooxygenase (PHM), the hydroxylating activity towards aliphatic substrates arises from the cooperative effect between two copper atoms, but the detailed mechanism has yet to be fully clarified. Herein, we report on a model complex showing hydroxylation of an aliphatic ligand initiated by dioxygen. According to DFT calculations, the proton-coupled electron-transfer (PCET) process leading to ligand hydroxylation in this complex benefits from cooperative effects between the two copper atoms. While one copper atom is responsible for dioxygen binding and activation, the other stabilizes the product of intramolecular PCET by copper–ligand charge transfer. The results of this work might pave the way for the directed utilization of cooperative effects in oxidation reactions.     

Triangular trinuclear metal-N4 complexes with high electrocatalytic activity for oxygen reduction

A new class of macrocyclic metal-N(4) complexes [MN(4)](n) (M = Co and Fe) were designed and synthesized based on a triangular ligand. Their unique triangular trinuclear structure provides a high density of active sites and facilitates the reduction of dioxygen via a four-electron pathway. Among them, a [CoN(4)](3)/C catalyst (20 wt %) exhibits high catalytic activity and long-time stability for the oxygen reduction reaction (ORR) in alkaline conditions, superior to the commercial Pt/C catalyst. Such structurally well-defined [MN(4)](n) complexes provide a platform for a new generation of nonprecious metal catalysts (NPMCs) for fuel cell applications.     

Oxygen economy of cytochrome P450: what is the origin of the mixed functionality as a dehydrogenase-oxidase enzyme compared with its normal function?

The economy of dioxygen consumption by enzymes constitutes a fundamental problem in enzymatic chemistry (ref 1). Sometimes, the enzyme converts ALL the oxygen into water, without affecting the organic substrate, thereby acting as an "oxidase" (ref 1). Other times, the enzyme converts all the oxygen into water and causes desaturation in the substrate, thus exhibiting a mixed function as both "oxidase" and "dehydrogenase" (refs 2-5). The present paper describes density functional calculations demonstrating that the oxidase-dehydrogenase mixed activity occurs from the cationic intermediate species and requires electro-steric inhibition of the rebound process. Furthermore, the calculations reveal that the carbocation is formally nascent from an excited state of the active species of the enzyme (2Cpd I), in which the Fe=O moiety is singlet coupled as in the 1Deltag state of dioxygen! Thus, our results resolve an important mechanism and reveal the factors that underlie its observability.     

A hybrid density functional study of O-O bond cleavage and phenyl ring hydroxylation for a biomimetic non-heme iron complex

Density functional calculations using the B3LYP functional have been used to study the reaction mechanism of [Fe(Tp(Ph2))BF] (Tp(Ph2) = hydrotris(3,5-diphenylpyrazol-1-yl)borate; BF = benzoylformate) with dioxygen. This mononuclear non-heme iron(II) complex was recently synthesized, and it proved to be the first biomimetic complex reproducing the dioxygenase activity of alpha-ketoglutarate-dependent enzymes. Moreover, the enthalpy and entropy of activation for this biologically interesting process were derived from kinetic experiments offering a unique possibility for direct comparison of theoretical and experimental data. The results reported here support a mechanism in which oxidative decarboxylation of the keto acid is the rate-limiting step. This oxygen activation process proceeds on the septet potential energy surface through a transition state for a concerted O-O and C-C bond cleavage. In the next step, a high-valent iron-oxo species performs electrophilic attack on the phenyl ring of the Tp(Ph2) ligand leading to an iron(III)-radical sigma-complex. Subsequent proton-coupled electron-transfer yields an iron(II)-phenol intermediate, which can bind dioxygen and reduce it to a superoxide radical. Finally, the protonated superoxide radical leaves the first coordination sphere of the iron(III)-phenolate complex and dismutates to dioxygen and hydrogen peroxide. The calculated activation barrier (enthalpy and entropy) and the overall reaction energy profile agree well with experimental data. A comparison to the enzymatic process, which is suggested to occur on the quintet surface, has been made.     

A Mechanistic Dichotomy in Two-Electron Reduction of Dioxygen Catalyzed by N,N’-Dimethylated Porphyrin Isomers

Selective two-electron reduction of dioxygen (O₂) to hydrogen peroxide (H₂O₂) has been achieved by two saddle-distorted N,N’-dimethylated porphyrin isomers, an N21,N’22-dimethylated porphyrin ( anti -Me₂P ) and an N21,N’23-dimethylated porphyrin ( syn -Me₂P ) as catalysts and ferrocene derivatives as electron donors in the presence of protic acids in acetonitrile. The higher catalytic performance in an oxygen reduction reaction (ORR) was achieved by anti -Me₂P with higher turnover number (TON=250 for 30 min) than that by syn -Me₂P (TON=218 for 60 min). The reactive intermediates in the catalytic ORR were confirmed to be the corresponding isophlorins ( anti -Me₂Iph or syn -Me₂Iph ) by spectroscopic measurements. The rate-determining step in the catalytic ORRs was concluded to be proton-coupled electron-transfer reduction of O₂ with isophlorins based on kinetic analysis. The ORR rate by anti -Me₂Iph was accelerated by external protons, judging from the dependence of the observed initial rates on acid concentrations. In contrast, no acceleration of the ORR rate with syn -Me₂Iph by external protons was observed. The different mechanisms in the O₂ reduction by the two isomers should be derived from that of the arrangement of hydrogen bonding of a O₂ with inner NH protons of the isophlorins.     

Dioxygen reactivity of new bispidine-copper complexes

The reactivity of copper complexes of three different second-generation bispidine-based ligands (bispidine = 3,7-diazabicyclo[3.3.1]nonane; mono- and bis-tetradentate; exclusively tertiary amine donors) with dioxygen [(reversible) binding of dioxygen by copper(I)] is reported. The UV-vis, electrospray ionization mass spectrometry, electron paramagnetic resonance, and vibrational spectra (resonance Raman) of the dioxygen adducts indicate that, depending on the ligand and reaction conditions, several different species (mono- and dinuclear, superoxo, peroxo, and hydroperoxo), partially in equilibrium with each other, are formed. Minor changes in the ligand structure and/or experimental conditions (solvent, temperature, relative concentrations) allow switching between the different forms. With one of the ligands, an end-on peroxodicopper(II) complex and a mononuclear hydroperoxocopper(II) complex could be characterized. With another ligand, reversible dioxygen binding was observed, leading to a metastable superoxocopper(II) complex. The amount of dioxygen involved in the reversible binding to Cu(I) was determined quantitatively. The mechanism of dioxygen binding as well as the preference of each of the three ligands for a particular dioxygen adduct is discussed on the basis of a computational (density functional theory) analysis.     

Distal metal effects in cobalt porphyrins related to CcO

Cobalt(II) porphyrins were studied to determine the influence of distal site metalation and superstructure upon dioxygen reactivity in active site models of cytochrome c oxidase (CcO). Monometallic, Co(II)(P) complexes when ligated by an axial imidazole react with dioxygen to form reversible Co-superoxide adducts, which were characterized by EPR and resonance Raman (RR). Unexpectedly, certain Co porphyrins with Cu(I) metalated imidazole pickets do not form mu-peroxo Co(III)/Cu(II) products even though the calculated intermetallic distance suggests this is possible. Instead, cobalt-porphyrin-superoxide complexes are obtained with the distal copper remaining as Cu(I). Moreover, distal metals (Cu(I) or Zn(II)) greatly enhance the stability of the dioxygen adduct, such that Co superoxides of bimetallic complexes demonstrate minimal reversibility. The "trapping" of dioxygen by a second metal is attributed to structural and electrostatic changes within the distal pocket upon metalation. EPR evidence suggests that the terminal oxygen in these bimetallic Co-superoxide systems is H-bonded to the NH of an imidazole picket amide linker, which may contribute to enthalpic stabilization of the dioxygen adduct. Stabilization of the dioxygen adduct in these bimetallic systems suggests one possible role for the distal copper in the Fe/Cu bimetallic active site of terminal oxidases, which form a heme-superoxide/copper(I) adduct upon oxygenation.     

Reaction coordinate analysis for beta-diketone cleavage by the non-heme Fe2+-dependent dioxygenase Dke1

Acetylacetone dioxygenase from Acinetobacter johnsonii (Dke1) utilizes a non-heme Fe2+ cofactor to promote dioxygen-dependent conversion of 2,4-pentanedione (PD) into methylglyoxal and acetate. An oxidative carbon-carbon bond cleavage by Dke1 is triggered from a C-3 peroxidate intermediate that performs an intramolecular nucleophilic attack on the adjacent carbonyl group. But how does Dke1 bring about the initial reduction of dioxygen? To answer this question, we report here a reaction coordinate analysis for the part of the Dke1 catalytic cycle that involves O2 chemistry. A weak visible absorption band (epsilon approximately 0.2 mM(-1) cm(-1)) that is characteristic of an enzyme-bound Fe2+-beta-keto-enolate complex served as spectroscopic probe of substrate binding and internal catalytic steps. Transient and steady-state kinetic studies reveal that O2-dependent conversion of the chromogenic binary complex is rate-limiting for the overall reaction. Linear free-energy relationship analysis, in which apparent turnover numbers (k(app) cat) for enzymatic bond cleavage of a series of substituted beta-dicarbonyl substrates were correlated with calculated energies for the highest occupied molecular orbitals of the corresponding beta-keto-enolate structures, demonstrates unambiguously that k(app) cat is governed by the electron-donating ability of the substrate. The case of 2'-hydroxyacetophenone (2'HAP), a completely inactive beta-dicarbonyl analogue that has the enol double bond delocalized into the aromatic ring, indicates that dioxygen reduction and C-O bond formation cannot be decoupled and therefore take place in one single kinetic step.     

Toward understanding macrocycle specificity of iron on the dioxygen-binding ability: a theoretical study

In an effort to examine the interaction between dioxygen and iron-macrocyclic complexes, and to understand how this interaction was affected by those different macrocyclic ligands, dioxygen binding with iron-porphyrin, iron-phthalocyanine, iron-dibenzotetraaza[14]annulene, and iron-salen complexes is investigated by means of quantum chemical calculations utilizing Density Functional Theory (DFT). Based on the analysis of factors influencing the corresponding dioxygen binding process, it showed that different macrocyclic ligands possess different O-O bond distances, and different electronic configurations for the bound O(2) and non-aromatic macrocyclic ligands favor dioxygen activation. Furthermore, the smaller the energy gap between the HOMO of iron-macrocyclic complexes and the LUMO of dioxygen, the more active the bound O(2) becomes, with a longer O-O bond distance and a shorter Fe-O bond length.     

Dioxygen activation in methane monooxygenase: a theoretical study

Using broken-symmetry unrestricted Density Functional Theory, the mechanism of enzymatic dioxygen activation by the hydroxylase component of soluble methane monooxygenase (MMOH) is determined to atomic detail. After a thorough examination of mechanistic alternatives, an optimal pathway was identified. The diiron(II) state H(red) reacts with dioxygen to give a ferromagnetically coupled diiron(II,III) H(superoxo) structure, which undergoes intersystem crossing to the antiferromagnetic surface and affords H(peroxo), a symmetric diiron(III) unit with a nonplanar mu-eta(2):eta(2)-O(2)(2)(-) binding mode. Homolytic cleavage of the O-O bond yields the catalytically competent intermediate Q, which has a di (mu-oxo)diiron(IV) core. A carboxylate shift involving Glu243 is essential to the formation of the symmetric H(peroxo) and Q structures. Both thermodynamic and kinetic features agree well with experimental data, and computed spin-exchange coupling constants are in accord with spectroscopic values. Evidence is presented for pH-independent decay of H(red) and H(peroxo). Key electron-transfer steps that occur in the course of generating Q from H(red) are also detailed and interpreted. In contrast to prior theoretical studies, a requisite large model has been employed, electron spins and couplings have been treated in a quantitative manner, potential energy surfaces have been extensively explored, and quantitative total energies have been determined along the reaction pathway.     

Mechanism of four-electron reduction of dioxygen to water by ferrocene derivatives in the presence of perchloric acid in benzonitrile, catalyzed by cofacial dicobalt porphyrins

The selective two-electron reduction of dioxygen occurs in the case of a monocobalt porphyrin [Co(OEP)], whereas the selective four-electron reduction of dioxygen occurs in the case of a cofacial dicobalt porphyrin [Co(2)(DPX)]. The other cofacial dicobalt porphyrins [Co(2)(DPA), Co(2)(DPB), and Co(2)(DPD)] also catalyze the two-electron reduction of dioxygen, but the four-electron reduction is not as efficient as in the case of Co(2)(DPX). The micro-superoxo species of cofacial dicobalt porphyrins were produced by the reactions of cofacial dicobalt(II) porphyrins with dioxygen in the presence of a bulky base and the subsequent one-electron oxidation of the resulting micro-peroxo species by iodine. The superhyperfine structure due to two equivalent cobalt nuclei was observed at room temperature in the ESR spectra of the micro-superoxo species. The superhyperfine coupling constant of the micro-superoxo species of Co(2)(DPX) is the largest among those of cofacial dicobalt porphyrins. This indicates that the efficient catalysis by Co(2)(DPX) for the four-electron reduction of dioxygen by Fe(C(5)H(4)Me)(2) results from the strong binding of the reduced oxygen with Co(2)(DPX) which has a subtle distance between two cobalt nuclei for the oxygen binding. Mechanisms of the catalytic two-electron and four-electron reduction of dioxygen by ferrocene derivatives will be discussed on the basis of detailed kinetics studies on the overall catalytic reactions as well as on each redox reaction in the catalytic cycle. The turnover-determining step in the Co(OEP)-catalyzed two-electron reduction of dioxygen is an electron transfer from ferrocene derivatives to Co(OEP)(+), whereas the turnover-determining step in the Co(2)(DPX)-catalyzed four-electron reduction of dioxygen changes from the electron transfer to the O-O bond cleavage of the peroxo species of Co(2)(DPX), depending on the electron donor ability of ferrocene derivatives.