The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.

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How mitochondria produce reactive oxygen species.

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

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Nitric Oxide and Peroxynitrite in Health and Disease

Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Role of free radicals and catalytic metal ions in human disease: an overview.

In this review, we highlight the use of organic photoredox catalysts in a myriad of synthetic transformations with a range of applications. This overview is arranged by catalyst class where the photophysics and electrochemical characteristics of each is discussed to underscore the differences and advantages to each type of single electron redox agent. We highlight both net reductive and oxidative as well as redox neutral transformations that can be accomplished using purely organic photoredox-active catalysts. An overview of the basic photophysics and electron transfer theory is presented in order to provide a comprehensive guide for employing this class of catalysts in photoredox manifolds.

Organic Photoredox Catalysis

1. Advantages of Chemical Redox Agents 878 2. Disadvantages of Chemical Redox Agents 879 C. Potentials in Nonaqueous Solvents 879 D. Reversible vs Irreversible ET Reagents 879 E. Categorization of Reagent Strength 881 II. Oxidants 881 A. Inorganic 881 1. Metal and Metal Complex Oxidants 881 2. Main Group Oxidants 887 B. Organic 891 1. Radical Cations 891 2. Carbocations 893 3. Cyanocarbons and Related Electron-Rich Compounds 894

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Chemical Redox Agents for Organometallic Chemistry

How super is superoxide

The goal of this book is to outline the basic principles and modern methodology of electrochemistry, in such away that the uninitiated may gain sufficient background to use electrochemical methods for the study of chemical systems. Thus chemical problems that are amenable to an electrochemical approach are introduced as representative examples. We hope by this approach to give the reader the necessary background to assess intelligently the most appropriate electrochemical technique for the study of a specific chemical problem.

Experimental Electrochemistry for Chemists

A complete and practical guide to the basic principles of electrochemistry for the nonspecialistEmphasizing practical applications and real-world experimentation, Electrochemistry for Chemists gives chemists, biologists, and material scientists a solid understanding of the basic principles and modern methodology of electrochemistry. Incorporating the many new applications of recent years, this thoroughly updated Second Edition gives the nonelectrochemist access to a powerful tool for the study and measurement of chemical systems. And, like the popular first edition, the Second Edition is also a useful text for senior undergraduate and graduate students, especially in organic, inorganic, and biological chemistry.* Offers a practical guide to the use of electrochemical methods in research and laboratory work* Provides examples of molecular characterization by electrochemical methods in all subdivisions of chemistry, including dioxygen species, base metals, and nonmetals* Includes numerous tables of electrochemical data, as well as physical parameters for solvents, electrolytes, cells, and electrodes* Incorporates the latest information on instrumentation, solvents, and reagents* Lists extensive references for further study of theoretical issues

Electrochemistry for Chemists

Effects of media and electrode materials on the electrochemical reduction of dioxygen

Opening Remarks- Dioxygen Complexes with Transition Metals- Bonding of Dioxygen to Transition Metals- Oxygen Binding by the Metalloproteins Hemerythrin, Hemocyanin, and Hemoglobin- Metal Oxo Complexes and Oxygen Activation- Kinetics of Formation of Biological Oxygen Carriers- Synthetic Dioxygen Carriers for Dioxygen Transport- Formation and Degradation of Cobalt Dioxygen Complexes- Reversible Complexes for the Recovery of Dioxygen- Summary - Dioxygen Complexes with Transition Metals- Oxygen Activation by Transition Metals- Summary - Oxygen Activation by Transition Metals- The Chemistry and Activation of Dioxygen Species (02, 02-, and H00H) in Biology- Oxygen Activation by Neutrophils- Mechanisms of Dioxygen Activation in Metal-Containing Monooxygenases: Enzymes and Model Systems- Radical Cation Pathways for Selective Catalytic Oxidation by Molecular Oxygen- Vanadium Catalyzed Autoxidation of Hydrogen Sulfide- Copper Catalyzed Oxidative Carbonylation of Methanol to Dimethyl Carbonate- Dependence of Reaction Pathways and Product Distribution on the Oxidation State of Palladium Catalysts for the Reactions of Olefinic and Aromatic Substrates with Molecular Oxygen- Oxygen Activation and Oxidation Reactions on Metal Surfaces- Methane Oxidation at Metal Oxide Surfaces- The Activation of Oxygen by Metal Phosphorus Oxides - The Vanadium Phosphorus Oxide Catalyst- The Oxidation of Organic Compounds by Metal Complexes in Zeolites- Abstracts of Posters- Kinetics and Mechanisms of Degradation of Binuclear Cobalt Dioxygen Complexes- Methane Activation over Lanthanide Oxides- Dioxygen Affinities of Some Synthetic Cobalt Schiff Base Complexes- Temporal Analysis of Products (TAP): A Unique Catalyst Evaluation System with Sub-Millisecond Time Resolution- Dioxygen Insertion into Metal-Carbon Bonds of Metalloporphyrins: Formation and Characterization of Alkylperoxy Metalloporphyrins- Iron Porphyrin Catalyzed Air Oxidation of Aldehydes and Alkenes- Oxidative Dimerization of Methane over Sodium-Promoted Calcium Oxides- Synthesis and Metal Ion Affinities of a Binucleating Polyamine: Reversible Formation of a Cobalt Dioxygen Complex- Potentiometric Determination of Stabilities of Cobalt(II) Complexes of Polyamine Schiff Bases and Their Dioxygen Adducts- Catalysis of Cobalt Schiff Base Complexes for the Oxygenation of Olefins Mechanisms for the Ketonization Reaction- Selective Oxidation of Saturated Hydrocarbons by the Gif and Gif-Orsay Systems- The Formation, Characterization, and Reactivity of the Oxene Adduct of Tetrakis(2,6-dichlorophenyl)porphinato-Iron(III) Perchlorate in Acetonitrile- Preparation and Characterization of a Binuclear Iron(III)- Hydroxo-y-hydroperoxy Complex [(Ph3PO)4(HO)FeIII(HOOH)FeIII(OH)(OPPh3)4](C1O4)4- Autoxidation of FeII(dihydroxyphenanthroline)3- Phosphine-Ruthenium(II)-Aquo Redox Chemistry: The Aerobic Catalytic Oxidation of Cyclohexene- The Oxidation of Organic Substrates by Molecular Oxygen Catalysis by Ru(III) and Ru(III)-EDTA- Oxygenation of Tryptophane Catalyzed by Polyamine Cobalt Dioxygen Complexes- Resonance Raman Spectroscopy of the Fe(IV)=0 Group in Peroxidase Intermediates- Reaction of Dioxygen with Synthetic Copper(I) Compounds of Biological Relevance- Thorough Elucidation of Oxygenation- and Oxidation-Mechanisms of Iron(II) Porphyrin on the Basis of a New Hypothesis for an Electron-Transfer Pathway- IUCCP Description

Donald T. Sawyer

Papers

How super is superoxide

Experimental Electrochemistry for Chemists

Electrochemistry for Chemists

Effects of media and electrode materials on the electrochemical reduction of dioxygen

Oxygen complexes and oxygen activation by transition metals