Superoxide Complex Research Articles

Superoxide to Peroxide Interconversion in Ni-TMC Complexes: The Significance of Structure and Spin States.

A deeper comprehension of the characteristics of metal-superoxide and metal-peroxide chemical species is imperative, considering their pivotal functions in oxygen transport, enzymatic activation, and catalytic oxygenations. O2 activation is mediated by the interconversion of superoxide and peroxide species. Even though there are multiple studies on metal-superoxide and -peroxide intermediates, robust examples of their interconversion processes are scarce synthetically. For example, Ni-superoxide/peroxide complexes have been characterized with N-Tetramethylated Cyclam (TMC) ligands with different ring sizes, i.e., Nickel(II)-superoxide complex is characterized with 14-TMC while Nickel(III)-peroxide complex with 12-TMC. Later, both complexes were obtained with 13-TMC ligand by employing different bases; interestingly, no evidence of interconversion between them was identified. What are the factors influencing these processes and why is this preference? We attempt a computational analysis of this issue and provide arguments based on our conclusions. 2-dimensional potential energy scan is performed on the 12-TMC, 13-TMC, and 14-TMC systems to identify the reaction path connecting superoxide and peroxide species. Analyses indicate that structure and spin states play a significant role in determining the probability of interconversion. The superoxide-peroxide interconversion process appears to be bound by their propensity for distinct structural features and spin states.

A Nonheme Iron(III) Superoxide Complex Leads to Sulfur Oxygenation.

A new alkylthiolate-ligated nonheme iron complex, FeII(BNPAMe2S)Br (1), is reported. Reaction of 1 with O2 at -40 °C, or reaction of the ferric form with O2•- at -80 °C, gives a rare iron(III)-superoxide intermediate, [FeIII(O2)(BNPAMe2S)]+ (2), characterized by UV-vis, 57Fe Mössbauer, ATR-FTIR, EPR, and CSIMS. Metastable 2 then converts to an S-oxygenated FeII(sulfinate) product via a sequential O atom transfer mechanism involving an iron-sulfenate intermediate. These results provide evidence for the feasibility of proposed intermediates in thiol dioxygenases.

Sulfonamido-Pincer Complexes of Cu(II) and the Electrocatalysis of O2 Reduction.

Heteroleptic copper complexes of an asymmetrical pincer ligand containing a central anionic sulfonamide donor (pyridine-2-yl-sulfonyl)(quinolin-8-yl)-amide (psq), which contains a central anionic sulfonamido donor have been prepared. Meridional κ3-N,N″,N‴ binding with the co-ligands acetate, chloride, or acetonitrile (MeCN), trans to the central sulfonamido N-donor, is revealed by the X-ray crystal structures of [Cu(OAc)(psq)(H2O)], [CuCl(psq)]2, and [Cu(psq)(MeCN)](PF6). Either overall distorted square pyramidal or octahedral geometries of the copper atom are satisfied by coordinated water in the case of the acetate complex or interactions with periphery sulfonamido oxygen atoms on adjacent molecules in the dimeric chloride and 1D polymeric acetonitrile complexes. The cyclic voltammogram (CV) of [Cu(OAc)(psq)(H2O)] shows a quasi-reversible CuII/CuI reduction at -0.930 V (vs Fc+/Fc0, MeCN), and an irreversible CuII/CuI reduction for [Cu(psq)(MeCN)](PF6) is seen at -0.838 V. This signal is split into two quasi-reversible redox processes on the addition of 2,2,2-trifluoroethanol (TFE). This suggests that TFE pushes a solution equilibrium toward a dimeric acetate complex analogous to [CuCl(psq)]2, which shows two quasi-reversible waves at -0.666 V and -0.904 V vs Fc+/Fc0 consistent with its dimeric solid-state structure. A comparison of the CVs of [Cu(OAc)(psq)(H2O)] under either a N2 or an O2 atmosphere revealed that this complex catalyzes turnover electro-reduction of O2 to H2O2 and H2O. The rate of reaction increases on addition of a weak organic acid, and a coulombic efficiency of 48% for H2O2 was determined by iodometric titration. We propose that a CuI complex formed on electroreduction binds O2 to yield an intermediate superoxide complex. On electron and proton transfer to this species, a bifurcated route back to the O2-activating CuI complex is feasible with either release of H2O2 or O-O cleavage resulting in the liberation of H2O. The CuI complex is regenerated by subsequent reduction and protonation to close the cycle.

An integrated multi-level analysis reveals learning-memory deficits and synaptic dysfunction in the rat model exposure to austere environment

Austere environment existing in tank, submarine and vessel has many risk factors including high temperature and humidity, confinement, noise, hypoxia, and high level of carbon dioxide, which may cause depression and cognitive impairment. However, the underlying mechanism is not fully understood yet. We attempt to investigate the effects of austere environment (AE) on emotion and cognitive function in a rodent model. After 21 days of AE stress, the rats exhibit depressive-like behavior and cognitive impairment. Compared with control group, the glucose metabolic level of the hippocampus is significantly decreased using whole-brain positron emission tomography (PET) imaging, and the density of dendritic spines of the hippocampus is remarkably reduced in AE group. Then, we employ a label-free quantitative proteomics strategy to investigate the differentially abundant proteins in rats' hippocampus. It is striking that the differentially abundant proteins annotated by KEGG enrich in oxidative phosphorylation pathway, synaptic vesicle cycle pathway and glutamatergic synapses pathway. The synaptic vesicle transport related proteins (Syntaxin-1A, Synaptogyrin-1 and SV-2) are down-regulated, resulting in the accumulation of intracellular glutamate. Furthermore, the concentration of hydrogen peroxide and malondialdehyde is increased while the activity of superoxide dismutase and complex I and IV of mitochondria is decreased, indicating that oxidative damage to hippocampal synapses is associated with the cognitive decline. The results of this study offer direct evidence, for the first time, that austere environment can substantially cause learning and memory deficits and synaptic dysfunction in a rodent model via behavioral assessments, PET imaging, label-free proteomics, and oxidative stress tests. SignificanceThe incidence of depression and cognitive decline in military occupations (for example, tanker and submariner) is significantly higher than that of global population. In the present study, we first established novel model to simulate the coexisting risk factors in the austere environment. The results of this study offer the direct evidences, for the first time, that the austere environment can substantially cause learning and memory deficits by altering plasticity of the synaptic transmission in a rodent model via proteomic strategy, PET imaging, oxidative stress and behavioral assessments. These findings provide valuable information to better understand the mechanisms of cognitive impairment.

Mechanistic Insight into Peptidyl-Cysteine Oxidation by the Copper-Dependent Formylglycine-Generating Enzyme.

The copper-dependent formylglycine-generating enzyme (FGE) catalyzes the oxygen-dependent oxidation of specific peptidyl-cysteine residues to formylglycine. Our QM/MM calculations provide a very likely mechanism for this transformation. The reaction starts with dioxygen binding to the tris-thiolate CuI center to form a triplet CuII -superoxide complex. The rate-determining hydrogen atom abstraction involves a triplet-singlet crossing to form a CuII -OOH species that couples with the substrate radical, leading to a CuI -alkylperoxo intermediate. This is accompanied by proton transfer from the hydroperoxide to the S atom of the substrate via a nearby water molecule. The subsequent O-O bond cleavage is coupled with the C-S bond breaking that generates the formylglycine and a CuII -oxyl complex. Moreover, our results suggest that the aldehyde oxygen of the final product originates from O2 , which will be useful for future experimental work.

Spectroelectrochemical one-electron reduction product of (TPP)Zn in nonaqueous media? Not always the expected porphyrin π-anion radical

Zinc tetraphenylporphyrin (TPP)Zn was examined as to its as to its electroreduction properties by cyclic voltammetry and spectroelectrochemistry in six nonaqueous solvents containing tetrabutylammonium perchlorate (TBAP). The porphyrin undergoes an initial one-electron reduction to give a [Formula: see text]-anion radical on the cyclic voltammetry timescale but the radical was not stable on the spectroelectrochemical timescale when utilizting chlorinated alkane solvents containing 0.1 M TBAP (CH2Cl2, 1-2,dichloroethane (C2H4Cl[Formula: see text] where chloride, generated from minute amounts of reduced solvent, formed an axially coordinated complex, (TPP)Zn[Formula: see text](Cl[Formula: see text], prior to reduction of the porphyrin. This spectroelectrochemically characterized product exhibits red-shifted Soret and Q-bands as compared to that of the neutral (TPP)Zn under the same solution conditions and analytical plots obtained from recording the spectrum as a function of potential rule out the possibility of forming the superoxide complex, (TPP)Zn[Formula: see text](O[Formula: see text], in chlorinated alkane solvents.

Mechanistic Insights into Cobalt-Based Water Oxidation Catalysis by DFT-Based Molecular Dynamics Simulations.

We report the mechanistic details of the water oxidation process by the complex, [CoII(bpbH2)Cl2], where bpbH2 = N, N'-bis(2'-pyridinecarboxamide)-1,2-benzene. An experimental study reported the complex as the efficient catalyst for the water oxidation process. We performed density functional theory calculations at the M06-L level and first-principles molecular dynamics simulations to study the catalytic nature of the complex. We investigated the energetics of the total catalytic cycle, which combines the oxygen-oxygen bond formation, proton-coupled electron transfer (PCET) steps, and release of oxygen molecule. The formed peroxide and superoxide intermediates in the catalytic cycle were characterized with the help of the Mulliken spin density parameters. Mulliken spin densities of the metal-oxo bond reveal that the triplet state of CoV═O has a double-bond nature, but the quintet state of the complex has a radical nature (CoIV-O•-). In an alternative way, the deprotonation of the amide groups of the ligand is also considered. The deprotonation and formation of higher oxidation metal-oxo intermediates are also possible. In addition to this, we have considered the effect of phosphate buffer on water nucleophilic addition. The oxygen-oxygen bond formation is favorable by the catalyst with the deprotonated form of the ligand, with the addition of water as the nucleophile. In the oxidation process, the C═O bonds of the ligand transfer the electron density to nitrogen atoms, stabilizing the higher order oxo, peroxide, and superoxide bonds. The oxygen-oxygen bond formation is the rate-determining step in the overall water oxidation process. This bond was further investigated using first-principles molecular dynamics at the PBE-D2 level. The dynamics of proton, hydroxide ion, and the nature of the ligand structure on the oxygen-oxygen bond were examined. We find that the oxygen molecule is released from the superoxide complex with the addition of water molecules.

Surface-chemistry-driven water dissociation on cobalt-based graphene hybrid from molecular dynamics simulations.

We explore the water dissociation process of graphene hybridized with a Co-bipyridine complex through first principles molecular dynamics simulations. We compute the free energies of the three main steps of the water dissociation process catalyzed by this hybrid catalyst. During the oxygen-oxygen bond formation, the transfer of the proton to the cis-OH of the cobalt complex is the rate determining step. The formation of the oxygen-oxygen bond leads to the peroxide complex, which is converted to the superoxide complex through the proton-coupled electron transfer (PCET) process. The formed superoxide complex is the rate-determining intermediate from which the oxygen molecule releases. The electronic properties of each state of the process were examined through Lowdin and Mulliken population analyses, local density of states (LDOS), and Wannier center analysis. The detailed electronic analysis reveals that the graphene sheet takes electronic density from the complex during the oxygen-oxygen bond formation. During the PCET process, the sheet shares the electron density with the complex, which stabilizes the superoxide complex. The Wannier center analysis provides evidence of the variation in the oxidation states of the metal center.

Mechanistic Insight into the O2 Evolution Catalyzed by Copper Complexes with Tetra- and Pentadentate Ligands

The mononuclear complexes ([(bztpen)Cu] (BF4)2 (bztpen = N-benzyl-N,N',N'-tris (pyridin-2-yl methyl ethylenediamine))) and ([(dbzbpen)Cu(OH2)] (BF4)2 (dbzbpen = N,N'-dibenzyl-N,N'-bis(pyridin-2-ylmethyl) ethylenediamine)) have been reported as water oxidation catalysts in basic medium (pH = 11.5). We explore the O2 evolution process catalyzed by these copper catalysts with various ligands (L) by applying the first-principles molecular dynamics simulations. First, the oxidation of catalysts to the metal-oxo intermediates [LCu(O)]2+ occurs through the proton-coupled electron transfer (PCET) process. These intermediates are involved in the oxygen-oxygen bond formation through the water-nucleophilic addition process. Here, we have considered two types of oxygen-oxygen bond formation. The first one is the transfer of the hydroxide of the water molecule to the Cu═O moiety; the proton transfer to the solvent leads to the formation of the peroxide complex ([LCu(OOH)]+). The other is the formation of the hydrogen peroxide complex ([LCu(HOOH)]2+) by the transfer of proton and hydroxide of the water molecule to the metal-oxo intermediate. The formation of the peroxide complex requires less activation free energy than hydrogen peroxide formation for both catalysts. We found two transition states in the well-tempered metadynamics simulations: one for proton transfer and another for hydroxide transfer. In both cases, the proton transfer requires higher free energy. Following the formation of the oxygen-oxygen bond, we study the release of the dioxygen molecule. The formed peroxide and hydrogen peroxide complexes are converted into the superoxide complex ([LCu(OO)]2+) through the transfer of proton, electron, and PCET processes. The superoxide complex releases an oxygen molecule upon the addition of a water molecule. The free energy of activation for the release of the dioxygen molecule is lesser than that of the oxygen-oxygen bond formation. When we observe the entire water oxidation process, the oxygen-oxygen bond formation is the rate-determining step. We calculated the rates of reaction by using the Eyring equation and found them to be close to the experimental values.

Ferric Heme Superoxide Reductive Transformations to Ferric Heme (Hydro)Peroxide Species: Spectroscopic Characterization and Thermodynamic Implications for H‐Atom Transfer (HAT)

AbstractA new end‐on low‐spin ferric heme peroxide, [(PIm)FeIII−(O22−)]− (PIm‐P), and subsequently formed hydroperoxide species, [(PIm)FeIII−(OOH)] (PIm‐HP) are generated utilizing the iron‐porphyrinate PIm with its tethered axial base imidazolyl group. Measured thermodynamic parameters, the ferric heme superoxide [(PIm)FeIII−(O2⋅−)] (PIm‐S) reduction potential (E°′) and the PIm‐HP pKa value, lead to the finding of the OO−H bond‐dissociation free energy (BDFE) of PIm‐HP as 69.5 kcal mol−1 using a thermodynamic square scheme and Bordwell relationship. The results are validated by the observed oxidizing ability of PIm‐S via hydrogen‐atom transfer (HAT) compared to that of the F8 superoxide complex, [(F8)FeIII−(O2.−)] (S) (F8=tetrakis(2,6‐difluorophenyl)porphyrinate, without an internally appended axial base imidazolyl), as determined from reactivity comparison of superoxide complexes PIm‐S and S with the hydroxylamine (O‐H) substrates TEMPO‐H and ABNO‐H.

Ferric Heme Superoxide Reductive Transformations to Ferric Heme (Hydro)Peroxide Species: Spectroscopic Characterization and Thermodynamic Implications for H-Atom Transfer (HAT).

A new end-on low-spin ferric heme peroxide, [(PIm )FeIII -(O22- )]- (PIm -P), and subsequently formed hydroperoxide species, [(PIm )FeIII -(OOH)] (PIm -HP) are generated utilizing the iron-porphyrinate PIm with its tethered axial base imidazolyl group. Measured thermodynamic parameters, the ferric heme superoxide [(PIm )FeIII -(O2⋅- )] (PIm -S) reduction potential (E°') and the PIm -HP pKa value, lead to the finding of the OO-H bond-dissociation free energy (BDFE) of PIm -HP as 69.5 kcal mol-1 using a thermodynamic square scheme and Bordwell relationship. The results are validated by the observed oxidizing ability of PIm -S via hydrogen-atom transfer (HAT) compared to that of the F8 superoxide complex, [(F8 )FeIII -(O2.- )] (S) (F8 =tetrakis(2,6-difluorophenyl)porphyrinate, without an internally appended axial base imidazolyl), as determined from reactivity comparison of superoxide complexes PIm -S and S with the hydroxylamine (O-H) substrates TEMPO-H and ABNO-H.

Computational mechanistic study on molecular catalysis of water oxidation by cyclam ligand-based iron complex

The iron metal complexes containing cyclam-based macrocyclic ligands are active water oxidation catalysts, which can facilitate oxygen–oxygen bond formation during the water-splitting process. To understand the mechanism of the catalytic process, we explored this process by [Fe(cyclam)Cl2]Cl performing density functional theory-based first-principles calculations. We examined the energetics of the formation of the oxygen–oxygen bond through the investigation of complexes [FeV(cyclam)(O)2]+, and [FeV(cyclam)(OH)(O)]+2. The process of water nucleophilic addition by this FeV–(oxo) complexes was explored in detail. Our computational study confirms the formation of these species, which were reported earlier in experimental conditions. The transition states for various reactions of the catalytic cycle were obtained within the implicit water model. From these calculations, we find that the proton transfers to cis–oxo or hydroxide moiety require high activation energy during the formation of the oxygen–oxygen bond. Our calculations reveal that the oxygen–oxygen bond formation by the transfer of a proton to the explicit water molecule requires more activation free energy than the transfer of a proton to the cis–oxo or hydroxide of the FeV–oxo species. Overall [FeV(cyclam)(O)2]+ and [FeV(cyclam)(OH)(O)]+2 species with one explicit water molecule requires similar free energy. The Mulliken spin density data confirm the formation of the superoxide complexes. The activation free energy for the release of the oxygen molecule is lesser than that of the oxygen–oxygen bond formation. The natural bond orbital analysis for the complexes before and after the formation of the oxygen–oxygen bond formation shows that this bond formation happens through the interaction of antibonding orbital, π*(d2 −2 –2py) of Fe=O moiety, with the σ*–orbital of the hydroxide group of the water molecule.

The mechanism of Metal-H2O2 complex immobilized on MCM-48 and enhanced electron transfer for effective peroxone ozonation of sulfamethazine

In the peroxone process (O3/H2O2), OH yield ratio with respect to O3 consumption was low due to the competition experiments. Singular effectiveness of CoCe as a supporting ligand in the interface of ozone-H2O2-catalysts and related complexes formed on catalysts enhanced the electron transfer between ozone chain reaction and various chemical state of Ce/Co. A computationally determined stereochemical structure corroborated that the CoCe synergistic effect led to the region around Co atom (electron donor) with low Gibbs free energy to form OH. Meanwhile, reactive oxygen species (ROSs) were tend to attack the sites with very negative natural population charge or high frontier electron density (FED) values of sulfamethazine (SMT) by LC–MS/MS and density functional theory (DFT) calculations. Benefiting from the unique superoxide complexes and synergetic effect of CoCe, the Co10Ce10@MCM-48 catalysts showed superior performance of SMT mineralization (64.1 %, 120 min), which resolved the low-efficient ROSs generation in bare peroxone reaction.

Routes to Heterotrinuclear Metal Siloxide Complexes for Cooperative Activation of O2.

The assembly of heterometallic complexes capable of activating dioxygen is synthetically challenging. Here, we report two different approaches for the preparation of heterometallic superoxide complexes [PhL2CrIII-η1-O2][MX]2 (PhL = -OPh2SiOSiPh2O-, MX+ = [CoCl]+, [ZnBr]+, [ZnCl]+) starting from the CrII precursor complex [PhL2CrII]Li2(THF)4. The first strategy proceeds via the exchange of Li+ by [MX]+ through the addition of MX2 to [PhL2CrII]Li2(THF)4 before the reaction with dioxygen, whereas in the second approach a salt metathesis reaction is undertaken after O2 activation by adding MX2 to [PhL2CrIII-η1-O2]Li2(THF)4. The first strategy is not applicable in the case of redox-active metal ions, such as Fe2+ or Co2+, as it leads to the oxidation of the central chromium ion, as exemplified with the isolation of [PhL2CrIIICl][CoCl]2(THF)3. However, it provided access to the hetero-bimetallic complexes [PhL2CrIII-η1-O2][MX]2 ([MX]+ = [ZnBr]+, [ZnCl]+) with redox-inactive flanking metals incorporated. The second strategy can be applied not only for redox-inactive but also for redox-active metal ions and led to the formation of chromium(III) superoxide complexes [PhL2CrIII-η1-O2][MX]2 (MX+ = [ZnCl]+, [ZnBr]+, [CoCl]+). The results of stability and reactivity studies (employing TEMPO-H and phenols as substrates) as well as a comparison with the alkali metal series (M+ = Li+, Na+, K+) confirmed that although the stability is dependent on the Lewis acidity of the counterions M and the number of solvent molecules coordinated to those, the reactivity is strongly dependent on the accessibility of the superoxide moiety. Consequently, replacement of Li+ by XZn+ in the superoxides leads to more stable complexes, which at the same time behave more reactive toward O-H groups. Hence, the approaches presented here broaden the scope of accessible heterometallic O2 activating compounds and provide the basis for further tuning of the reactivity of [RL2CrIII-η1-O2]M2 complexes.

On the Mechanism of the Reaction between Thiolate-Protected Gold Clusters and Molecular Oxygen: What is Activated?

The various energy pathways of Au20(SCH3)16 oxidation were simulated in the gas phase and on a CeO2 surface at the density functional theory/Perdew–Burke–Ernzerhof (DFT/PBE) level. Due to the high stability and strong Au–S bonds of the protected cluster, there was no stable complex with oxygen. Alternative processes were considered: oxidation of staple (AuSCH3)x fragments and the cluster, in which one, two, and three thiolate ligands were removed (Au20(SCH3)16–x, x = 1–3). It was shown that peroxide and superoxide complexes formed only if the cluster fragments reacted with singlet oxygen. Oxygen was sufficiently absorbed on Au20(SCH3)16–x. The structures of Au20(SCH3)16 and Au20(SCH3)16–x on the CeOx surface were studied in detail. After deposition of the cluster on ceria, the thiolate ligands were lost. Oxygen was activated on Au20(SCH3)13/CeOx near the particle–support interface (the adsorption energy was −112 kJ/mol).

Heme-FeIII Superoxide, Peroxide and Hydroperoxide Thermodynamic Relationships: FeIII-O2•- Complex H-Atom Abstraction Reactivity.

Establishing redox and thermodynamic relationships between metal-ion-bound O2 and its reduced (and protonated) derivatives is critically important for a full understanding of (bio)chemical processes involving dioxygen processing. Here, a ferric heme peroxide complex, [(F8)FeIII-(O22-)]- (P) (F8 = tetrakis(2,6-difluorophenyl)porphyrinate), and a superoxide complex, [(F8)FeIII-(O2•-)] (S), are shown to be redox interconvertible. Using Cr(η-C6H6)2, an equilibrium state where S and P are present is established in tetrahydrofuran (THF) at -80 °C, allowing determination of the reduction potential of S as -1.17 V vs Fc+/0. P could be protonated with 2,6-lutidinium triflate, yielding the low-spin ferric hydroperoxide species, [(F8)FeIII-(OOH)] (HP). Partial conversion of HP back to P using a derivatized phosphazene base gave a P/HP equilibrium mixture, leading to the determination of pKa = 28.8 for HP (THF, -80 °C). With the measured reduction potential and pKa, the O-H bond dissociation free energy (BDFE) of hydroperoxide species HP was calculated to be 73.5 kcal/mol, employing the thermodynamic square scheme and Bordwell relationship. This calculated O-H BDFE of HP, in fact, lines up with an experimental demonstration of the oxidizing ability of S via hydrogen atom transfer (HAT) from TEMPO-H (2,2,6,6-tetramethylpiperdine-N-hydroxide, BDFE = 66.5 kcal/mol in THF), forming the hydroperoxide species HP and TEMPO radical. Kinetic studies carried out with TEMPO-H(D) reveal second-order behavior, kH = 0.5, kD = 0.08 M-1 s-1 (THF, -80 °C); thus, the hydrogen/deuterium kinetic isotope effect (KIE) = 6, consistent with H-atom abstraction by S being the rate-determining step. This appears to be the first case where experimentally derived thermodynamics lead to a ferric heme hydroperoxide OO-H BDFE determination, that FeIII-OOH species being formed via HAT reactivity of the partner ferric heme superoxide complex.

Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O-H and C-H Substrates.

The dioxygen reactivity of a series of TMPA-based copper(I) complexes (TMPA=tris(2-pyridylmethyl)amine), with and without secondary-coordination-sphere hydrogen-bonding moieties, was studied at -135 °C in 2-methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H-bonded [( TMPA)CuII (O2.- )]+ cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( TMPA)CuII (N3- )]+ azido analogues were compared, and the O2.- reactivity of ligand-CuI complexes when an H-bonding moiety is replaced by a methyl group was contrasted. A drastic enhancement in the reactivity of the cupric superoxide towards phenolic substrates as well as oxidation of substrates possessing moderate C-H bond-dissociation energies is observed, correlating with the number and strength of the H-bonding groups.

Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O−H and C−H Substrates

AbstractThe dioxygen reactivity of a series of TMPA‐based copper(I) complexes (TMPA=tris(2‐pyridylmethyl)amine), with and without secondary‐coordination‐sphere hydrogen‐bonding moieties, was studied at −135 °C in 2‐methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H‐bonded [( TMPA)CuII(O2.−)]+ cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( TMPA)CuII(N3−)]+ azido analogues were compared, and the O2.− reactivity of ligand–CuI complexes when an H‐bonding moiety is replaced by a methyl group was contrasted. A drastic enhancement in the reactivity of the cupric superoxide towards phenolic substrates as well as oxidation of substrates possessing moderate C−H bond‐dissociation energies is observed, correlating with the number and strength of the H‐bonding groups.

Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: The alleviating effect and its mechanism of Polygonatum kingianum

BackgroundMitochondrial dysfunction is an important mechanism of non-alcoholic fatty liver disease (NAFLD). Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for NAFLD therapy. In China, Polygonatum kingianum (PK) has been used as a herb and food nutrient for centuries. So far, studies in which the effects of PK on NAFLD are evaluated are lacking. Our study aims at identifying the effects and mechanism of action of PK on NAFLD based on mitochondrial regulation. MethodsA NAFLD rat model was induced by a high-fat diet (HFD) and rats were intragastrically given PK (1, 2 and 4 g/kg) for 14 weeks. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in oxidative stress, energy metabolism, fatty acid metabolism, and apoptosis were investigated. ResultsPK significantly inhibited the HFD-induced increase of alanine transaminase, aspartate transaminase, total cholesterol (TC), and low density lipoprotein cholesterol in serum, and TC and triglyceride in the liver. In addition, PK reduced high density lipoprotein cholesterol and liver enlargement without affecting food intake. PK also remarkably inhibited the HFD-induced increase of malondialdehyde and the reduction of superoxide dismutase, glutathione peroxidase, ATP synthase, and complex I and II, in mitochondria. Moreover, mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2 was significantly up-regulated and down-regulated after PK treatment, respectively. Finally, PK notably inhibited the HFD-induced increase of caspase 9, caspase 3 and Bax expression in hepatocytes, and the decrease of expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria. ConclusionPK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD.

Mechanistic Dichotomy in Proton-Coupled Electron-Transfer Reactions of Phenols with a Copper Superoxide Complex.

The kinetics and mechanism(s) of the reactions of [K(Krypt)][LCuO2] (Krypt = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane, L = a bis(arylcarboxamido)pyridine ligand) with 2,2,6,6-tetramethylpiperdine- N-hydroxide (TEMPOH) and the para-substituted phenols XArOH (X = para substituent NO2, CF3, Cl, H, Me, tBu, OMe, or NMe2) at low temperatures were studied. The reaction with TEMPOH occurs rapidly ( k = 35.4 ± 0.3 M-1 s-1) by second-order kinetics to yield TEMPO• and [LCuOOH]- on the basis of electron paramagnetic resonance spectroscopy, the production of H2O2 upon treatment with protic acid, and independent preparation from reaction of [NBu4][LCuOH] with H2O2 ( Keq = 0.022 ± 0.007 for the reverse reaction). The reactions with XArOH also follow second-order kinetics, and analysis of the variation of the k values as a function of phenol properties (Hammett σ parameter, O-H bond dissociation free energy, p Ka, E1/2) revealed a change in mechanism across the series, from proton transfer/electron transfer for X = NO2, CF3, Cl to concerted-proton/electron transfer (or hydrogen-atom transfer) for X = OMe, NMe2 (data for X = H, Me, tBu are intermediate between the extremes). Thermodynamic analysis and comparisons to previous results for LCuOH, a different copper-oxygen intermediate with the same supporting ligand, and literature for other [CuO2]+ complexes reveal significant differences in proton-coupled electron-transfer mechanisms that have implications for understanding oxidation catalysis by copper-containing enzymes and abiological catalysts.