The Role of Iron Oxides in Marine Phosphorus Cycling

Dissolved and particulate phase iron (Fe) and phosphorus (P) concentrations were characterized in Effingham Inlet, a fjord located on the west coast of Vancouver Island. The effect of redox conditions on Fe and P cycling was investigated through comparison of sediment and water samples taken above and below a water column redox boundary in the fjord. The data show that sharp increases in the concentration of dissolved P across the redox boundary cannot be explained solely by release of absorbed phosphorus associated with dissolution of iron oxide phases. These findings support new theories of P cycling in oceans, which suggest that redox sensitive cycling of polyphosphates by microorganisms may be a significant source of dissolved phosphorus in marine environments.Ellery Ingall - Faculty Mento

Reversible Anionic Redox Activities in Conventional LiNi1/3 Co1/3 Mn1/3 O2 Cathodes.

Redox reactions of oxygen have been considered critical in controlling the electrochemical properties of lithium-excessive layered-oxide electrodes. However, conventional electrode materials without overlithiation remain the most practical. Typically, cationic redox reactions are believed to dominate the electrochemical processes in conventional electrodes. Herein, we show unambiguous evidence of reversible anionic redox reactions in LiNi1/3 Co1/3 Mn1/3 O2 . The typical involvement of oxygen through hybridization with transition metals is discussed, as well as the intrinsic oxygen redox process at high potentials, which is 75 % reversible during initial cycling and 63 % retained after 10 cycles. Our results clarify the reaction mechanism at high potentials in conventional layered electrodes involving both cationic and anionic reactions and indicate the potential of utilizing reversible oxygen redox reactions in conventional layered oxides for high-capacity lithium-ion batteries

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson\u27s Disease

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress. Redox reactions involve transfer of one or more electrons between two compounds resulting in either oxidation or reduction. In redox cycling, a compound undergoes alternate oxidation and reduction, transferring electrons from a reductant to molecular oxygen. Therefore, we began by investigating different modes of redox cycling by measuring the rate of oxygen consumption using a Clark-type oxygen electrode in the presence of different reductants. We compared chemically synthesized redox cyclers such as menadione, 6-hydroxydopamine (6-OHDA), 3-methyl-5-anilino-1,2- benzoquinone (3-MAQ) and 9,10-phenanthrenequinone, using ascorbic acid and dithiothreitol (DTT) as reductants. Addition of superoxide dismutase diminished DTT dependent redox cycling activity (except in the case of menadione) but had no effect on the ascorbate-dependent redox cycling activity. This suggests that DTT drives a two electron reduction whereas ascorbate causes a one-electron reduction. NADHdependent redox cycling mediated by mitochondria was also studied using 3-MAQ. This mitochondrially mediated redox cycling activity was inhibited by mersalyl acid, thereby suggesting the involvement of the outer-mitochondrial membrane protein, NADH dependent cytochrome b5 reductase, in the redox cycling mechanism. We identified hypochlorite-oxidized cysteinyl-dopamine (HOCD) as a redox cycling product and a potential candidate for dopaminergic neuron toxicity in the progression of Parkinson’s disease. The dopamine oxidation product cysteinyl-dopamine has attracted attention as a contributor to the death of dopaminergic neurons in Parkinson’s disease. Treatment of cysteinyl-dopamine with hypochlorite yields an even more cytotoxic product. This product, HOCD, has potent redox-cycling activity and initiates production of superoxide in PC12 cells. Taurine, which scavenges hypochlorite, protects PC12 cells from cysteinyl-dopamine but not from HOCD, suggesting that HOCD, not cysteinyl-dopamine itself, is toxic. Furthermore, rotenone, which enhances expression of the hypochlorite-producing enzyme myeloperoxidase, increases the cytotoxicity of cysteinyl-dopamine but not of HOCD. This suggests that dopamine oxidation to cysteinyl-dopamine followed by hypochlorite-dependent conversion to a cytotoxic redox-cycling product HOCD, leads to the generation of reactive oxygen species and oxidative stress and may contribute to the death of dopaminergic neurons. Our findings of HOCD toxicity in PC12 cells was followed by our study to determine the mode of cell death. The morphological changes in the cell such as membrane blebbing and appearance of biochemical markers such as cleaved poly-ADP ribose polymerase and active caspase-9 suggested cell death by apoptosis. Moreover, increased expression of tumor suppressor protein p53, indicated mitochondrial mediated apoptotic cell death. Our observations have raised an unappreciated possibility that may link dopamine oxidation, microglial inflammation, oxidative stress and the rotenone model of Parkinson’s disease. Furthermore, it offers a promising new approach in the search for a therapeutic cure for Parkinson’s disease

Identification of Enzymes Causing Redox Cycling, Causing Oxidative Stress and Damaging Mitochondria

Oxidative stress is thought to contribute to the death of dopamine neurons and the consequential progression of Parkinson’s disease. Redox cycling of quinones, including compounds formed by dopamine oxidation, can lead to oxidative stress and damaging of the mitochondria. Which enzymes catalyze the redox cycling of quinones is unknown, however. Inhibitors of the mitochondrial respiratory chain (cyanide, rotenone) do not inhibit redox cycling. Mitochondrial NAD(P)H:quinone oxidoreductases are likely candidates, but dicumarol, a common inhibitor of such enzymes is not effective. We observed that Cibacron Blue does indeed inhibit NADH-dependent redox cycling to an extent. Our data shows that the rate of oxygen consumption decreased with the addition of Cibacron Blue. Moreover, the changes in the mitochondrial membrane potential, indicated by fluorescence of the rhodamine dye bound to the membrane, are less significant when the inhibitor was added. Cibacron Blue inhibits a quinone:oxidoreductase enzyme and has important implications for the causes of Parkinson’s disease. Moreover, another inhibitor, mersalyl acid, has also been identified as a potentially more effective blocker to redox cycling, based on the drastic decrease in oxygen consumption upon its addition

Naphthoquinone-mediated inhibition of lysine acetyltransferase KAT3B/p300, basis for non-toxic inhibitor synthesis

Hydroxynaphthoquinone-based inhibitors of the lysine acetyltransferase KAT3B (p300), such as plumbagin, are relatively toxic. Here, we report that free thiol reactivity and redox cycling properties greatly contribute to the toxicity of plumbagin. A reactive 3rd position in the naphthoquinone derivatives is essential for thiol reactivity and enhances redox cycling. Using this clue, we synthesized PTK1, harboring a methyl substitution at the 3rd position of plumbagin. This molecule loses its thiol reactivity completely and its redox cycling ability to a lesser extent. Mechanistically, non-competitive, reversible binding of the inhibitor to the lysine acetyltransferase (KAT) domain of p300 is largely responsible for the acetyltransferase inhibition. Remarkably, the modified inhibitor PTK1 was a nearly non-toxic inhibitor of p300. The present report elucidates the mechanism of acetyltransferase activity inhibition by 1,4-naphthoquinones, which involves redox cycling and nucleophilic adduct formation, and it suggests possible routes of synthesis of the non-toxic inhibitor

Dissociate lattice oxygen redox reactions from capacity and voltage drops of battery electrodes.

The oxygen redox (OR) activity is conventionally considered detrimental to the stability and kinetics of batteries. However, OR reactions are often confused by irreversible oxygen oxidation. Here, based on high-efficiency mapping of resonant inelastic x-ray scattering of both the transition metal and oxygen, we distinguish the lattice OR in Na0.6[Li0.2Mn0.8]O2 and compare it with Na2/3[Mg1/3Mn2/3]O2. Both systems display strong lattice OR activities but with distinct electrochemical stability. The comparison shows that the substantial capacity drop in Na0.6[Li0.2Mn0.8]O2 stems from non-lattice oxygen oxidations, and its voltage decay from an increasing Mn redox contribution upon cycling, contrasting those in Na2/3[Mg1/3Mn2/3]O2. We conclude that lattice OR is not the ringleader of the stability issue. Instead, irreversible oxygen oxidation and the changing cationic reactions lead to the capacity and voltage fade. We argue that lattice OR and other oxygen activities should/could be studied and treated separately to achieve viable OR-based electrodes

Development of Dual-Electrode Amperometric Detectors for Liquid Chromatography and Capillary Electrophoresis

Abstract The body of this research was focused on the use and development dual-electrode detection schemes for liquid chromatography and capillary electrophoresis. These detection schemes were developed to investigate redox chemistries for endogenous and exogenous antioxidants that play key roles in maintaining tissue redox homeostasis under oxidative stress conditions. A parallel adjacent dual electrode detector was first proposed for liquid chromatography in which redox cycling was hypothesized to occur between the electrodes resulting in signal enhancement. Flow rates for these systems were too high (≥ 1.0 mL) to obtain redox cycling and subsequently no signal enhancement was observed for these systems. Flow rates in capillary electrophoresis are significantly lower compared to liquid chromatography. Therefore, a parallel dual–electrode was developed for capillary electrophoresis in this work. The dual–electrode was investigated using reduced phenolic acids, which were chemically reversible, semi–reversible and non-reversible compounds allowing all potential electrochemistry’s to be investigated. Redox cycling and signal enhancement was observed with the developed dual–electrode. Furthermore, the parallel dual–electrode could be operated in either a redox cycling mode or dual–potential mode, where either chemical reversibility or voltammetry could be used as a means to confirm migration based peak identification, respectively. The same design was then applied for a dual Au/Hg electrode for capillary electrophoresis, in which thiols and disulfides were investigated in vivo. With the developed dual Au/Hg electrode redox changes were observed as a result of chemically induced oxidative stress

Differential Cyclic Voltammetry - a Novel Technique for Selective and Simultaneous Detection using Redox Cycling Based Sensors

Redox cycling (RC) is an effect that is used to amplify electrochemical signals. However, traditional techniques such as cyclic voltammetry (CV) do not provide clear insight for a mixture of multiple redox couples while RC is applied. Thus, we have developed a new measurement technique which delivers electrochemical spectra of all reversible redox couples present based on concentrations and standard potentials. This technique has been named differential cyclic voltammetry (DCV). We have fabricated micrometer-sized interdigitated electrode (IDE) sensors to conduct DCV measurements in mixtures of 1mM catechol and 4mM [Ru(NH3)6]Cl3. To simulate the electrochemical behavior of these sensors we have also developed a finite element model (FEM) in Comsol®. The\ud experimental data corresponds to the calculated spectra obtained from simulations. Additionally, the measured spectra can be used to easily derive standard potentials and concentrations simultaneously and selectively.\u