Extremely Fast Hydrogen Atom Transfer between Nitroxides and HOO· Radicals and Implication for Catalytic Coantioxidant Systems.

We report a novel coantioxidant system based on TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) that, in biologically relevant model systems, rapidly converts chain-carrying alkylperoxyl radicals to HOO·. Extremely efficient quenching of HOO· by TEMPO blocks the oxidative chain. Rate constants in chlorobenzene were measured to be 1.1 × 109 M-1 s-1 for the reductive reaction TEMPO + HOO· → TEMPOH + O2 and 5.0 × 107 M-1 s-1 for the oxidative reaction TEMPOH + HOO· → TEMPO + H2O2. These rate constants are significantly higher than that associated with the reaction of HOO· with α-tocopherol, Nature's best lipid soluble antioxidant ( k = 1.6 × 106 M-1 s-1). These data show that in the presence of ROO·-to-HOO· chain-transfer agents, which are common in lipophilic environments, the TEMPO/TEMPOH couple protects organic molecules from oxidation by establishing an efficient reductive catalytic cycle. This catalytic cycle provides a new understanding of the efficacy of the antioxidant capability of TEMPO in nonaqueous systems and its potential to act as a chemoprotective against radical damage.

• Publication year

  2018

• Venue

  Journal of the American Chemical Society

• Publication date

  2018-07-19

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/jacs.8b06336PMID 30022659
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Pro‐fluorescent mitochondria‐targeted real‐time responsive redox probes synthesised from carboxy isoindoline nitroxides: Sensitive probes of mitochondrial redox status in cells

  2018cited by this paper
• Electrochemical and Electrostatic Cleavage of Alkoxyamines.

  2018cited by this paper
• The Catalytic Reaction of Nitroxides with Peroxyl Radicals and Its Relevance to Their Cytoprotective Properties.

  2018cited by this paper
• A Bioresistant Nitroxide Spin Label for In-Cell EPR Spectroscopy: In Vitro and In Oocytes Protein Structural Dynamics Studies.

  2018cited by this paper
• New Spin on Organic Radical Batteries-An Isoindoline Nitroxide-Based High-Voltage Cathode Material.

  2018cited by this paper
• Antioxidant activity of nanomaterials.

  2018cited by this paper
• Inhibition of hydrocarbon autoxidation by nitroxide-catalyzed cross-dismutation of hydroperoxyl and alkylperoxyl radicals† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc01575a

  2018cited by this paper
• Biological Relevance of Free Radicals and Nitroxides

  2017cited by this paper
• Lipid Peroxidation: Kinetics, Mechanisms, and Products.

  2017cited by this paper
• Orthogonal Click Postfunctionalization of Alternating Copolymers Prepared by Nitroxide-Mediated Polymerization.

  2017cited by this paper
• Kinetics and Mechanism of Radical‐Chain Oxidation of 1,2‐Substituted Ethylene and 1,4‐Substituted Butadiene‐1,3

  2017cited by this paper
• Measuring Antioxidant Activity in Bioorganic Samples by the Differential Oxygen Uptake Apparatus: Recent Advances

  2017cited by this paper
• On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

  2017cited by this paper
• Nitroxides as Antioxidants and Anticancer Drugs

  2017cited by this paper
• Peroxyl Radical Reactions in Water Solution: A Gym for Proton-Coupled Electron-Transfer Theories.

  2016cited by this paper
• Novel Synthetic PEGylated Conjugate of α-Lipoic Acid and Tempol Reduces Cell Death in a Neuronal PC12 Clonal Line Subjected to Ischemia.

  2016cited by this paper
• Acid Is Key to the Radical-Trapping Antioxidant Activity of Nitroxides.

  2016cited by this paper
• A Mitochondrial-Targeted Nitroxide Is a Potent Inhibitor of Ferroptosis

  2016cited by this paper
• Hydroperoxyl Radicals (HOO. ): Vitamin E Regeneration and H-Bond Effects on the Hydrogen Atom Transfer.

  2016cited by this paper
• Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation.

  2016cited by this paper
• Multiple chain termination by aromatic nitroxides in oxidation of styrene

  2015cited by this paper
• Redox chemistry of selenenic acids and the insight it brings on transition state geometry in the reactions of peroxyl radicals.

  2014cited by this paper
• Performance of conventional and dispersion-corrected density-functional theory methods for hydrogen bonding interaction energies.

  2013cited by this paper
• Antioxidant activity of essential oils.

  2013cited by this paper
• The reaction of sulfenic acids with peroxyl radicals: insights into the radical-trapping antioxidant activity of plant-derived thiosulfinates.

  2012cited by this paper
• The ROS scavenging and renal protective effects of pH-responsive nitroxide radical-containing nanoparticles.

  2011cited by this paper
• DSD-PBEP86: in search of the best double-hybrid DFT with spin-component scaled MP2 and dispersion corrections.

  2011cited by this paper
• Effect of the damping function in dispersion corrected density functional theory

  2011cited by this paper
• Thermochemistry of proton-coupled electron transfer reagents and its implications.

  2010cited by this paper
• A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu.

  2010cited by this paper
• Mechanism of the aerobic oxidation of alpha-pinene.

  2010cited by this paper
• TEMPO reacts with oxygen-centered radicals under acidic conditions.

  2010cited by this paper
• Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions.

  2009cited by this paper
• The unusual reaction of semiquinone radicals with molecular oxygen.

  2008cited by this paper
• Lone pair-pi and pi-pi interactions play an important role in proton-coupled electron transfer reactions.

  2007cited by this paper
• Kinetics and mechanism of peroxyl radical reactions with nitroxides.

  2007cited by this paper
• The chemistry and biology of nitroxide compounds.

  2007cited by this paper
• Lone Pair−π and π−π Interactions Play an Important Role in Proton-Coupled Electron Transfer Reactions

  2007cited by this paper
• Solvent effects on the rates and mechanisms of reaction of phenols with free radicals.

  2007cited by this paper
• Semiempirical hybrid density functional with perturbative second-order correlation.

  2006cited by this paper
• A theoretical study of the iminoxyl/oxime self-exchange reaction. A five-center, cyclic proton-coupled electron transfer.

  2005cited by this paper
• New insight into solvent effects on the formal HOO. + HOO. reaction.

  2005cited by this paper
• Water effect on the o-h dissociation enthalpy of para-substituted phenols: a DFT study.

  2004cited by this paper
• A new hybrid exchange–correlation functional using the Coulomb-attenuating method (CAM-B3LYP)

  2004cited by this paper
• Mechanism of inhibition of lipid peroxidation by gamma-terpinene, an unusual and potentially useful hydrocarbon antioxidant.

  2003cited by this paper
• Thermolysis of N‐tetramethylpiperidinyl triphenylacetate: homolytic fragmentation of a TEMPO ester

  2003cited by this paper
• The role of oxoammonium cation in the SOD-mimic activity of cyclic nitroxides.

  2003cited by this paper
• Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen.

  2001cited by this paper
• Quantitative studies on the peroxidation of human low-density lipoprotein initiated by superoxide and by charged and neutral alkylperoxyl radicals.

  2001cited by this paper
• A complete basis set model chemistry. VII. Use of the minimum population localization method

  2000cited by this paper
• Density-functional thermochemistry. III. The role of exact exchange

  1993cited by this paper
• Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density.

  1988cited by this paper
• Absolute rate constants for hydrocarbon autoxidation. 31. Autoxidation of cumene in the presence of tertiary amines

  1981cited by this paper
• Absolute rate constants for hydrocarbon autoxidation. XIX. Oxidation of some α-substituted toluenes

  1970cited by this paper
• ABSOLUTE RATE CONSTANTS FOR HYDROCARBON AUTOXIDATION: I. STYRENE

  1965cited by this paper
• Bioinformatics Original Paper Copasi—a Complex Pathway Simulator

  year unknowncited by this paper

• Rational design of tetrahydrotetrazinones as potent nonclassical radical-trapping antioxidants for inhibition of ferroptosis.

  2026cites this paper
• Solvent Effects on C–H Abstraction by Hydroperoxyl Radicals: Implication for Antioxidant Strategies

  2025cites this paper
• Inhibited and non-inhibited lipid oxidation in colloidal solutions: A review

  2025cites this paper
• Intramolecular Hydrogen Atom Transfer Enables Hydroperoxyl Radical Formation during the Peroxidation of Unsaturated Lipids.

  2025cites this paper
• Tempo‐Functionalized Janus Hydrogel Crosslinked by Tandem Dynamic Covalent Bonds for Internal Organ Injury Repair and Deep Second‐Degree Burn Wound Healing

  2025cites this paper
• Inhibition of acrylic acid and acrylate autoxidation.

  2025cites this paper
• Photochemical and Oxidative Degradation of Chamazulene Contained in Artemisia, Matricaria and Achillea Essential Oils and Setup of Protection Strategies

  2024cites this paper
• Pro-aromatic Natural Terpenes as Unusual "Slingshot" Antioxidants with Promising Ferroptosis Inhibition Activity.

  2024cites this paper
• The effect of dual antioxidant modification on oxidative stress resistance and anti-dysfunction of non-split HDL and recombinant HDL.

  2024cites this paper
• Lipid Peroxidation and Antioxidant Protection

  2023influential citation
• Insight into the Antioxidant Activity of 1,8-Dihydroxynaphthalene Allomelanin Nanoparticles

  2023cites this paper
• The Synergy between Glutathione and Phenols—Phenolic Antioxidants Repair Glutathione: Closing the Virtuous Circle—A Theoretical Insight

  2023cites this paper
• Hydroperoxyl radical (HOO•) as a reducing agent: unexpected synergy with antioxidants. A review

  2023cites this paper
• Reaction with ROO• and HOO• Radicals of Honokiol-Related Neolignan Antioxidants

  2023cites this paper
• An atoms‐in‐molecules characterization of the nature of the OO bond in peroxides and nitroxide dimers

  2023cites this paper
• Melamine Barbiturate as a Light-Induced Nanostructured Supramolecular Material for a Bioinspired Oxygen and Organic Radical Trap and Stabilization

  2023cites this paper
• Enhancement of Diarylamine Antioxidant Activity by Molybdenum Dithiocarbamates.

  2023cites this paper
• Tandem Hydroperoxyl–Alkylperoxyl Radical Quenching by an Engineered Nanoporous Cerium Oxide Nanoparticle Macrostructure (NCeONP): Toward Efficient Solid-State Autoxidation Inhibitors

  2023cites this paper
• Mutual Activation of Two Radical Trapping Agents: Unusual “Win–Win Synergy” of Resveratrol and TEMPO during Scavenging of dpph• Radical in Methanol

  2022cites this paper
• The Underrecognized Role of the Hydroperoxyl (HOO•) Radical in Chain Propagation of Lipids and its Implication in Antioxidant Activity

  2022cites this paper
• New Insights into the Actual H-Abstraction Activities of Important Oxygen and Nitrogen Free Radicals: Thermodynamics and Kinetics in Acetonitrile

  2022cites this paper
• H/D Kinetic Solvent Isotope Effect in the Oxidation of Methyl Linoleate in Triton X-100 Micelles

  2022cites this paper
• Revisiting the Electrochemistry of TEMPOH Analogues in Acetonitrile.

  2022cites this paper
• Probing the efficiency of thermal and photochemical bond homolysis in functionalized nanostructured SBA-15 silicas

  2021cites this paper
• Two Faces of the Bi−O Bond: Photochemically and Thermally Induced Dehydrocoupling for Si−O Bond Formation

  2021cites this paper
• Expanding the spectrum of polydopamine antioxidant activity by nitroxide conjugation.

  2021cites this paper
• Catalytic inhibition of olefin oxidation with Mn and Cu compounds

  2021cites this paper
• Methods to Determine Chain-Breaking Antioxidant Activity of Nanomaterials beyond DPPH•. A Review

  2021cites this paper
• Mechanism of Electrochemical Generation and Decomposition of Phthalimide-N-oxyl.

  2021cites this paper
• Nitroxides as Building Blocks for Nanoantioxidants

  2021cites this paper
• Autoxidation vs. antioxidants - the fight for forever.

  2021cites this paper
• Temperature-Dependent Effects of Alkyl Substitution on Diarylamine Antioxidant Reactivity.

  2021cites this paper
• Hydrogen Atom Transfer from HOO. to ortho‐Quinones Explains the Antioxidant Activity of Polydopamine

  2021cites this paper
• The influence of medium polarity on the kinetics and mechanism of interaction of aliphatic nitroxides with hydroperoxyl radicals

  2021cites this paper
• Synergic antioxidant activity of γ-terpinene with phenols and polyphenols enabled by hydroperoxyl radicals.

  2020cites this paper
• Potent Ferroptosis Inhibitors Can Catalyze the Cross-Dismutation of Phospholipid-Derived Peroxyl Radicals and Hydroperoxyl Radicals.

  2020cites this paper
• Quantum chemical evaluation of the role of $${{{\text{HO}}_{2}}^{ \cdot }}$$HO2· radicals in the kinetics of the methyl linoleate oxidation in micelles

  2019cites this paper
• 1-Methyl-1,4-cyclohexadiene as a traceless reducing agent for the synthesis of catechols and hydroquinones.

  2019cites this paper
• Kinetics of oxidation of benzyl alcohols with molecular oxygen catalyzed by N ‐hydroxyphthalimide: Role of hydroperoxyl radicals

  2019cites this paper
• Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from Activated Phenols.

  2019cites this paper