Academic literature on the topic 'Futile redox cycling'

Methylenetetrahydrofolate reductase (MTHFR) links the folate cycle to the methionine cycle in one-carbon metabolism. The enzyme is known to be allosterically inhibited by SAM for decades, but the importance of this regulatory control to one-carbon metabolism has never been adequately understood. To shed light on this issue, we exchanged selected amino acid residues in a highly conserved stretch within the regulatory region of yeast MTHFR to create a series of feedback-insensitive, deregulated mutants. These were exploited to investigate the impact of defective allosteric regulation on one-carbon metabolism. We observed a strong growth defect in the presence of methionine. Biochemical and metabolite analysis revealed that both the folate and methionine cycles were affected in these mutants, as was the transsulfuration pathway, leading also to a disruption in redox homeostasis. The major consequences, however, appeared to be in the depletion of nucleotides. 13C isotope labeling and metabolic studies revealed that the deregulated MTHFR cells undergo continuous transmethylation of homocysteine by methyltetrahydrofolate (CH3THF) to form methionine. This reaction also drives SAM formation and further depletes ATP reserves. SAM was then cycled back to methionine, leading to futile cycles of SAM synthesis and recycling and explaining the necessity for MTHFR to be regulated by SAM. The study has yielded valuable new insights into the regulation of one-carbon metabolism, and the mutants appear as powerful new tools to further dissect out the intersection of one-carbon metabolism with various pathways both in yeasts and in humans.

1 Nitrofurantoin is an antimicrobial agent which pro duces hepatotoxicity caused by the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress. 2 Our goal was to determine treatment strategies which could mitigate nitrofurantoin-induced toxicity in the isolated perfused rat liver. We co-infused various agents which blocked early or late events in the progression to toxicity. Tissue levels of glutathione and protein thiols were measured as indicators of the progression to toxicity and lactate dehydrogenase leakage into the perfusate was used as a marker of irreversible cell death. 3 Five treatments significantly ( P < 0.05) decreased LDH leakage (reported as thousands of units accumulated in perfusate at 300 min, mean ± standard error, n=3- 4) when compared to nitrofurantoin alone (274 ±37). These treatments were adenosine-2'-monophosphate (120 ± 53), penicillamine (90 ± 29), N-(2-mercaptopro pionyl)-glycine (120 ± 49) and bromosulfophthalein with (80 ± 29) or without 5,5'-difluro-1,2-bis(O-amino phenoxy)ethane-N,N,N'N'-tetraacetic acid (101 ± 46). Two other treatments, N-acetylcysteine (183 ± 7) and dithiothreitol (166 ± 59) delayed the onset of toxicity. Finally, calpeptin (319 ± 34) which blocks activation of nonlysosomal proteases was ineffective. 4 We concluded that early intervention on the pathway to toxicity was most effective. The strategies detailed here may prove beneficial in treating hepatotoxicity seen following nitrofurantoin therapy.

1 Nitrofurantoin is an antimicrobial agent which pro duces pulmonary toxicity via the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress. 2 In the isolated perfused rat lung, nitrofurantoin induced a decrease in tissue levels of glutathione but not protein thiols by the end of the 180 min experi ment. There was no decline in tissue levels of angiotensin converting enzyme (a marker of cell disruption). However, edema was extensive as mon itored in real time by weight gain (2.71 ± 0.56 g vs 0.63 ± 0.53 g in control, P<0.05, n=4) and lung mechanical functioning. The edema was matched by an increase in lavage proteins (85 ± 15 mg vs 16 ± 9 mg in controls, P<0.05, n=4). Electron microscopic examination of tissue indicated that the endothelial cells were detached from the basement membrane which would account for the edema. 3 Co-infusion of penicillamine, N-acetylcysteine or N- (2-mercaptopropionyl)-glycine which can protect tissue from oxidative stress failed to mitigate NFT induced edema. Allopurinol, an inhibitor of xanthine oxidase and a metal chelator, significantly decreased weight gain but did not prevent the loss of glutathione. These results suggested that allopurinol was not blocking metabolic activation of NFT by xanthine oxidase but scavenging metal cations which can initiate and/or propagate the oxidative stress cascade. 4 We concluded that, in the isolated perfused rat lung, the classic pathway of oxidative stress induced by NFT is interrupted at the stage of GSH loss. These experiments demonstrated that organ function was compromised more than the individual cells. They also suggested that allopurinol may prove beneficial in modulating NFT pulmonary toxicity.

1. Introduction 682. Ferredoxin reduction by photosystem I 723. Ferredoxins 734. Ferredoxin[ratio ]thioredoxin reductase 734.1 Spectroscopic investigations of FTR 764.2 The three-dimensional structure of FTR from the cyanobacterium Synechocystis sp. PCC6803 774.2.1 The variable subunit 774.2.2 The catalytic subunit 814.2.3 The iron–sulfur center and active site disulfide bridge 824.2.4 The dimer 844.3 Thioredoxin f and m 854.4 Ferredoxin and thioredoxin interactions 864.5 Mechanism of action 884.6 Comparison with other chloroplast FTRs 925. Target enzymes 955.1 NADP-dependent malate dehydrogenase 955.1.1 Regulatory role of the N-terminal extension 975.1.2 Regulatory role of the C-terminal extension 995.1.3 Thioredoxin interactions 1015.2 Fructose-1,6-bisphosphatase 1015.3 Redox regulation of chloroplast target enzymes 1036. Conclusion 1037. Acknowledgements 1048. References 104A pre-requisite for life on earth is the conversion of solar energy into chemical energy by photosynthetic organisms. Plants and photosynthetic oxygenic microorganisms trap the energy from sunlight with their photosynthetic machinery and use it to produce reducing equivalents, NADPH, and ATP, both necessary for the reduction of carbon dioxide to carbohydrates, which are then further used in the cellular metabolism as building blocks and energy source. Thus, plants can satisfy their energy needs directly via the light reactions of photosynthesis during light periods. The situation is quite different in the dark, when these organisms must use normal catabolic processes like non-photosynthetic organisms to obtain the necessary energy by degrading carbohydrates, like starch, accumulated in the chloroplasts during daylight. The chloroplast stroma contains both assimilatory enzymes of the Calvin cycle and dissimilatory enzymes of the pentose phosphate cycle and glycolysis. This necessitates a strict, light-sensitive control that switches between assimilatory and dissimilatory pathways to avoid futile cycling (Buchanan, 1980, 1991; Buchanan et al. 1994; Jacquot et al. 1997; Schürmann & Buchanan, 2000).

The Pseudomonas aeruginosa secretory product pyocyanin damages lung epithelium, likely due to redox cycling of pyocyanin and resultant superoxide and H2O2generation. Subcellular site(s) of pyocyanin redox cycling and toxicity have not been well studied. Therefore, pyocyanin's effects on subcellular parameters in the A549 human type II alveolar epithelial cell line were examined. Confocal and electron microscopy studies suggested mitochondrial redox cycling of pyocyanin and extracellular H2O2release, respectively. Pyocyanin decreased mitochondrial and cytoplasmic aconitase activity, ATP levels, cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and mitochondrial membrane potential. These effects were transient at low pyocyanin concentrations and were linked to apparent cell-mediated metabolism of pyocyanin. Overexpression of MnSOD, but not CuZnSOD or catalase, protected cellular aconitase, but not ATP, from pyocyanin-mediated depletion. This suggests that loss of aconitase activity is not responsible for ATP depletion. How pyocyanin leads to ATP depletion, the mechanism of cellular metabolism of pyocyanin, and the impact of mitochondrial pyocyanin redox cycling on other cellular events are important areas for future study.

Abstract As the demand for rechargeable lithium-ion batteries (LIBs) with higher energy density increases, the interest in lithium-rich oxide (LRO) with extraordinarily high capacities is surging. The capacity of LRO cathodes exceeds that of conventional layered oxides. This has been attributed to the redox contribution from both cations and anions, either sequentially or simultaneously. However, LROs with notable anion redox suffer from capacity loss and voltage decay during cycling. Therefore, a fundamental understanding of their electrochemical behaviors and related structural evolution is a prerequisite for the successful development of high-capacity LRO cathodes with anion redox activity. However, there is still controversy over their electrochemical behavior and principles of operation. In addition, complicated redox mechanisms and the lack of sufficient analytical tools render the basic study difficult. In this review, we aim to introduce theoretical insights into the anion redox mechanism and in situ analytical instruments that can be used to prove the mechanism and behavior of cathodes with anion redox activity. We summarized the anion redox phenomenon, suggested mechanisms, and discussed the history of development for anion redox in cathode materials of LIBs. Finally, we review the recent progress in identification of reaction mechanisms in LROs and validation of engineering strategies to improve cathode performance based on anion redox through various analytical tools, particularly, in situ characterization techniques. Because unexpected phenomena may occur during cycling, it is crucial to study the kinetic properties of materials in situ under operating conditions, especially for this newly investigated anion redox phenomenon. This review provides a comprehensive perspective on the future direction of studies on materials with anion redox activity.

Realizing reversible reduction-oxidation (redox) reactions of lattice oxygen in batteries is a promising way to improve the energy and power density. However, conventional oxygen absorption spectroscopy fails to distinguish the critical oxygen chemistry in oxide-based battery electrodes. Therefore, high-efficiency full-range mapping of resonant inelastic X-ray scattering (mRIXS) has been developed as a reliable probe of oxygen redox reactions. Here, based on mRIXS results collected from a series of Li1.17Ni0.21Co0.08Mn0.54O2 electrodes at different electrochemical states and its comparison with peroxides, we provide a comprehensive analysis of five components observed in the mRIXS results. While all the five components evolve upon electrochemical cycling, only two of them correspond to the critical states associated with oxygen redox reactions. One is a specific feature at 531.0 eV excitation and 523.7 eV emission energy, the other is a low-energy loss feature. We show that both features evolve with electrochemical cycling of Li1.17Ni0.21Co0.08Mn0.54O2 electrodes, and could be used for characterizing oxidized oxygen states in the lattice of battery electrodes. This work provides an important benchmark for a complete assignment of all mRIXS features collected from battery materials, which sets a general foundation for future studies in characterization, analysis, and theoretical calculation for probing and understanding oxygen redox reactions.

Redox flow batteries (RFBs) have significant potential in grid-level electrical energy storage, generated by renewable sources such as wind or solar power. Of particular interest in this research are aqueous organic electrolyte systems due to their safety, cost, fast kinetics and greater sustainability compared to the use of conventional inorganic electrolytes or organic solvents. To date this area has been limited by both the solubility and long term cycling stability of organic electrolytes.1 The most difficult challenge in this field is the development of stable organic catholytes that have high redox potentials, high energy density, and high battery efficiency. Triarylamines (TAAs) have the potential to meet these criteria because of the ease of functional group modification allowing for variation of the redox potential, and the low reorganisation energy between the neutral and radical states.2,3 TAAs have previously been explored as catholyte materials in organic non-aqueous RFBs, with studies showing that the redox properties of these easily prepared compounds can be tuned by judicious choice of functional groups at the para positions.4 It was also shown that TAAs have high cycling stability compared to other popular catholytes such as TEMPOL.5 However, TAAs have not previously been used as catholytes in aqueous RFBs. In this work, a number of TAAs were explored with various substituents in the para-positions of their aromatic rings, with the aim of promoting good aqueous solubility and cycling stability (two of the main selection criteria for any RFB electrolyte). Tris-4-amino-phenyl amine was found to be the most promising candidate, with reversible redox at high positive potentials, ease of synthesis, and reasonable aqueous solubility. Extensive electrochemical investigations using cyclic voltammetry (CV), impedance and full cell cycling were carried out which provide clues as to how the TAA framework can be modified to improve the redox properties for future catholyte applications. Figure 1: Triarylamine framework containing various substituents and CV of 1mM Tris-4-amino-phenyl amine with a scan rate of 20 mV/s in 1 M HCl with a Ag/AgCl reference electrode, glassy carbon working electrode and platinum counter electrode 1 R. M. Darling, K. G. Gallagher, J. A. Kowalski, S. Ha and F. R. Brushett, Energy Environ. Sci., 2014, 7, 3459–3477. 2 Tohru Nishinaga, Organic Redox Systems, Synthesis, Properties and Applications, Wiley, 2016. 3 J. Wang, K. Liu, L. Ma and X. Zhan, Chem. Rev., 2016, 116, 14675–14725. 4 I. A. V. Romadina, Elena I., K. J. Stevensona and P. A. Troshin, Mater. Chem. A, 2021, 9, 8303–8307. 5 G. Kwon, K. Lee, J. Yoo, S. Lee, J. Kim, Y. Kim, J. E. Kwon, S. Y. Park and K. Kang, Energy Storage Mater., 2021, 42, 185–192. Figure 1

Redox flow batteries (RFBs) are very promising storage systems in the transition towards renewable energy sources. They can be broadly classified in aqueous and non-aqueous systems. Last-named operate with organic solvents, which allow for a much broader potential window (up to three times higher) compared to water. Combination of organic solvents with organic redox active materials could pave the way for all carbon-based RFBs with superior energy densities compared to aqueous systems. In this contribution, newly developed organic electrolytes will be presented, focusing on their performance as RFB materials in acetonitrile with quaternary ammonium electrolyte salts. To push the limits of energy density, we investigated multi-electron reduction and oxidation reactions on a single molecule. As catholyte, tetrathiafulvalene (TTF) as a core structure was used. The unsubstituted TTF exhibits two reversible oxidation events (-0.04 and +0.34 V vs Fc/Fc+) but a poor solubility in acetonitrile. To optimize this and to achieve a higher oxidation potential a series of molecules with different side chains was synthesized. The resulting solubilities led to volumetric capacities of up to 71 Ah/L for the newly designed compounds. Electrochemical cycling stability was evaluated in bulk electrolysis, UV-Vis-NIR and flow cycling experiments. Current state-of-the-art anolytes based on N-methylphthalimide compounds exhibit one reversible reduction pair at a desirable low reduction potential (-1.87 V vs Fc/Fc+) and good cycling stability in bulk electrolysis experiments.[1] Expanding on this structure, new derivatives with one or two additional functional imide groups per phthalimide core were synthesized. Consequently, molecules with a single (-1.87 V vs Fc/Fc+), double (-1.26 and -1.88 V vs Fc/Fc+) and triple reduction event (-1.02, -1.65 and -2.37 V vs Fc/Fc+) can be obtained. To optimize their solubility in acetonitrile, a series of molecules with different side chains was synthesized for each of the three core structures. Determination of the solubility led to volumetric capacities of up to 66 Ah/L for the newly developed compounds. Additionally, we tested the electrochemical cycling stability in bulk electrolysis, UV-Vis-NIR, coin cell and flow cycling experiments. In the final flow battery, a high energy density of 24 Wh/L was achieved (at 1 M of transferred electrons).[2] All of this led to a critical comparison between the different molecular designs, cumulating in design rules that will influence future designs of the organic redox active compounds for organic RFBs. [1] Wei, X.; Duan, W.; Huang, J.; Zhang, L.; Li, B.; Reed, D.; Xu, W.; Sprenkle, V.; Wang, W. A High-Current, Stable Nonaqueous Organic Redox Flow Battery. ACS Energy Lett. 2016, 1, 705−711 [2] Daub, N.; Janssen, R. A. J.; Hendriks, K. H. Imide-Based Multielectron Anolytes as High-Performance Materials in Nonaqueous Redox Flow Batteries. ACS Appl. Energy Mater. 2021, 4, 9, 9248–9257

The cytochrome P450 enzymes CYP101B1 and CYP101C1, which are from the aromatic hydrocarbon degrading bacterium Novosphingobium aromaticivorans DSM12444, can hydroxylate norisoprenoids with high activity and selectivity. With the aim of further understanding their substrate range, a selection of cyclic alkanes, ketones and alcohols were studied. Cycloalkanes were oxidised, but both enzymes displayed low binding affinity and productive activity. The presence of a ketone moiety in the cycloalkane skeleton significantly improved the substrate binding affinity and the oxidation activity. CYP101C1 catalysed the oxidation of the cycloalkanones at the C-2 position with high regioselectivity. The regioselectivity of CYP101B1 was different. It oxidised cycloalkanones at positions remote from the carbonyl group. This indicated that the binding orientation of the cyclic ketones in the active site of each enzyme must be different. Cyclic alcohols and cyclohexylacetic acid showed little to no activity with either enzyme. The introduction of an ester protecting group to these substrates significantly enhanced the monooxygenase activity. These substrates were oxidised regioselectively on the opposite side of the ring system to the ester directing group. For example, both enzymes preferentially oxidised the C-H bond at the C4, C5 and C7 position of the cyclohexyl, cyclooctyl and cyclododecyl ester compounds, respectively. In addition, certain linear ketones and esters were also found to be suitable substrates for these biocatalysts. CYP101B1 mediated metabolism of the tricyclic compounds adamantane, 1‐ and 2‐ adamantanol and 2‐adamantanone proceeds with low oxidation activity and multiple metabolites were identified. Insertion of a directing group (acetate/isobutyrate) at the alcohol of these adamantanols significantly increased the affinity, activity and coupling efficiency (productive use of reducing equivalents) of CYP101B1 compared to the parent compounds. This substrate engineering approach with these adamantyl derivatives led to a 65 to 122-fold higher product formation activity. The turnovers were also regioselective and in some instances stereoselective. Additionally, the amide N‐(1‐adamantyl)acetamide was oxidised efficiently by CYP101B1, whereas 1‐adamantylamine was not. Whole-cell biotransformation systems were used to generate the metabolites in good yield (g/L scale). Overall, the use of ester directing groups and the modification of the amine to an amide enabled CYP101B1 to oxidise the adamantane skeleton more efficiently and selectively. Wild-type (WT) CYP101B1 can catalyse the oxidation of aromatic substrates such as alkylbenzenes, alkylnaphthalenes and acenaphthene, but the binding affinities and the oxidation activities were low. Both the binding affinity and product formation activity of this enzyme for these hydrophobic substrates were enhanced using site-directed mutagenesis. The Histidine 85 (H85) of CYP101B1 aligns with tyrosine 96 of CYP101A1 (P450cam), which, in the latter enzyme forms the only hydrophilic interaction with its natural substrate, camphor. The H85 residue of CYP101B1 was therefore replaced with phenylalanine (F), and this H85F variant exhibited greater affinity and activity towards hydrophobic substrates. For instance, the product formation activity of the H85F variant for acenaphthene oxidation was increased sixfold to 245 nmol.nmol-CYP–1.min–1. This indicated that this residue is in the substrate binding pocket or the access channel of the enzyme. Methylcubanes have been used as mechanistic probes to differentiate between radical and cationic pathways in cytochrome P450 oxidation. A series of methylcubanes were designed which would place the methyl group close to reactive heme iron centre of CYP101B1. CYP101B1 efficiently oxidised the substituted methylcubane derivatives yielding the equivalent cubylmethanol in 93 ± 7 % yield. The cube was found to be intact in all the turnover products, and no methylcubanols or any other rearranged metabolites containing homocubyl were detected. These results were consistent with a rapid radical rebound step in these oxidations and argued against the involvement of any carbocation-based intermediates during the oxidation. The CYP101B1 system, which also combines a FAD-containing ferredoxin reductase and a [2Fe-2S] ferredoxin, was investigated with oxygenated aromatics including naphthols, naphthoquinones, dihydroxynaphthalene and phenols. In vitro NADH oxidation rates in both the presence and absence of CYP101B1 were fast with these substrates (≥800 min-1). Minimal metabolite formation was detected, and the majority of reducing equivalents were transformed into hydrogen peroxide. Large amount of H2O2 in these reactions in the absence of P450 indicated that the ferredoxin (Arx) and ferredoxin reductase (ArR) catalysed futile redox cycling with naphthoquinones giving rise to the uncoupling of the reducing equivalents. Further examination of naphthols and naphthoquinones together with 2-adamantyl acetate in the fully reconstituted CYP101B1 turnovers demonstrated that the presence of naphthoquinones led to diminished product formation as they interfere with the electron transfer process. This type of uncoupling in the bacterial P450 electron transfer partners containing ferredoxin system would be considered an additional form of uncoupling over those which arise in the P450 active site.
Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2019

Abstract For continuous operation of Concentrated Solar Power (CSP) Plants it is necessary to integrate thermal energy storage module. High-density energy storage system at a high temperature is required for the new generation of large scale CSP plants. The Thermochemical Energy Storage (TCES) systems use the enthalpy of formation of a reversible chemical reaction for energy storage and release. Gas/solid reduction-oxidation (redox) reactions of solid metal oxides using air as heat transfer fluid (HTF) can be directly integrated with air operated CSP plants, and there is no need for HTF storage and any intermediate heat exchanger. A new generation of large scale CSP plants uses high-temperature solar collectors to increase power cycle efficiency. Such operating conditions require the development of suitable high-temperature TCES systems. The selection of suitable metal oxide reactant is very critical in the design of such high-temperature storage systems and requires a detailed study of the physics of reaction within the reactor. Cobalt oxide (Co3O4/CoO) has been verified to have a high reaction temperature, high enthalpy of reaction together with reasonable cyclic and thermal stability. Unique features of cobalt oxide require more fundamental study of the physics behind the redox reaction and its cyclic performance. Study of the physics of materials during the storage/release cycle is necessary for the design and improvement of the reactor and can be used as a benchmark for comparison of any implemented changes. A high precision, true differential TGA/DSC instrument is used for simultaneous measurement of weightchange (TGA) and true differential heat flow (DSC) for pure cobalt oxide (Co3O4) powder. Storage cycle (charge/discharge) was conducted for five cycles. Complete re-oxidation was achieved within reasonable times by performing the two reactions at close temperatures and controlling heating/cooling rates. Basic performance parameters were derived as a benchmark for future references. Single-cycle controlling parameters such as heating/cooling rate, dwelling time, and purge gas rate were investigated. System response for few initial cycles was studied. It was shown that pure cobalt oxide could regain weight and complete re-oxidation with reasonable stability. A transition for heat flow was detected after a few initial cycles which reduced discharge heat and decreased overall performance.

Mercuric ion, inorganic metal ion, found in three oxidation state in nature, including elemental mercury (Hg0), mercurous ion (Hg+), and mercuric ion (Hg2+). These three forms possess hazardous environmental contaminant and are extremely toxic metal materials to damage mammalian organs.[1] This work demonstrates a label-free technique for Hg2+ ions detection using capped gold nanowire arrays based sensors[2] combined with the electrochemical surface plasmon resonance method. The three-electrode electrochemical analysis (Fig. 1) and optical transmission measurement were employed to characterize the potential-current responses and the resonant peak signals were for the investigation of metal ion electrodeposition (Fig. 2). The nanostructured EC-SPR sensors were used to characterize the eletrochemical behaviors of K3Fe(CN)6/K2Fe(CN)6 redox couple and evaluate the wavelength sensitivity (480.3 nm RIU-1) with a FOM of 40.0 RIU-1 and the intensity sensitivity (1819.9 %) in the glycerol-water solutions. Fig. shows the detection limit of 1 pM Hg2+ can be obtained by the chronoamperomet- ric-spectrum analysis. The developed capped gold nanowire arrays based sensors present Hg2+ ion selectivity over the wavelength shifts of the interfering ions including Ca2+, Co2+, Ni2+, Na+, Cu2+, Pb2+, and Mn2+ ions. The developed capped gold nanoslit arrays based sensors present Hg2+ ion selectivity over the wavelength shifts of the interfering ions including Ca2+, Co2+, Ni2+, Na+, Cu2+, Pb2+, and Mn2+ ions. The proposed flexible capped gold nanowire arrays based sensor is applicable to be an EC-SPR label-free platform and enabled a rapid, sensitive and selective sensing method for aqueous Hg2+ detection. The application of biomolecule analysis can be further evaluation in the future. applicable to be an EC-SPR label-free platform and enabled a rapid, sensitive and selective sensing method for aqueous Hg2+ detection. The application of biomolecule analysis can be further evaluation in the future. Fig.1.Schematic representation of electrochemical surface plasmon resonance configuration set-up for mercury ions detection. Fig. 2 Redox current curves during the first cyclic voltammetry scan and the simultaneously measured surface plasmon resonance intensity. Fig. 3. The wavelength shifts and the intensity changes of gold nanowire arrays against Hg2+concentrations between 100|rM and 100nM. The inset shows the reduction reaction currents of amperometric responses at various Hg2+ concentrations.