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Rafael Radi - One of the best experts on this subject based on the ideXlab platform.
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fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration
Redox biology, 2018Co-Authors: Silvina Bartesaghi, Rafael RadiAbstract:In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the Diffusion-Controlled Reaction between superoxide (O2•-) and nitric oxide (•NO). This process is in competition with the enzymatic dismutation of O2•- and the Diffusion of •NO across cells and tissues and its Reaction with molecular targets (e.g. guanylate cyclase). Understanding the kinetics and compartmentalization of the O2•- / •NO interplay is critical to rationalize the shift of •NO from a physiological mediator to a cytotoxic intermediate. Once formed, peroxynitrite (ONOO- and ONOOH; pKa = 6,8) behaves as a strong one and two-electron oxidant towards a series of biomolecules including transition metal centers and thiols. In addition, peroxynitrite anion can secondarily evolve to secondary radicals either via its fast Reaction with CO2 or through proton-catalyzed homolysis. Thus, peroxynitrite can participate in direct (bimolecular) and indirect (through secondary radical intermediates) oxidation Reactions; through these processes peroxynitrite can participate as cytotoxic effector molecule against invading pathogens and/or as an endogenous pathogenic mediator. Peroxynitrite can cause protein tyrosine nitration in vitro and in vivo. Indeed, tyrosine nitration is a hallmark of the Reactions of •NO-derived oxidants in cells and tissues and serves as a biomarker of oxidative damage. Protein tyrosine nitration can mediate changes in protein structure and function that affect cell homeostasis. Tyrosine nitration in biological systems is a free radical process that can be promoted either by peroxynitrite-derived radicals or by other related •NO-dependent oxidative processes. Recently, mechanisms responsible of tyrosine nitration in hydrophobic biostructures such as membranes and lipoproteins have been assessed and involve the parallel occurrence and connection with lipid peroxidation. Experimental strategies to reveal the proximal oxidizing mechanism during tyrosine nitration in given pathophysiologically-relevant conditions include mapping and identification of the tyrosine nitration sites in specific proteins.
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biochemistry of peroxynitrite and protein tyrosine nitration
Chemical Reviews, 2018Co-Authors: Gerardo Ferrersueta, Beatriz Alvarez, Silvina Bartesaghi, Madia Trujillo, Nicolas Campolo, Sebastian Carballal, Natalia Romero, Rafael RadiAbstract:Peroxynitrite is a short-lived and reactive biological oxidant formed from the Diffusion-Controlled Reaction of the free radicals superoxide (O2•–) and nitric oxide (•NO). In this review, we first analyze the biochemical evidence for the formation of peroxynitrite in vivo and the Reactions that lead to it. Then, we describe the principal Reactions that peroxynitrite undergoes with biological targets and provide kinetic and mechanistic details. In these Reactions, peroxynitrite has roles as (1) peroxide, (2) Lewis base, and (3) free radical generator. Physiological levels of CO2 can change the outcome of peroxynitrite Reactions. The second part of the review assesses the formation of protein 3-nitrotyrosine (NO2Tyr) by peroxynitrite-dependent and -independent mechanisms, as one of the hallmarks of the actions of •NO-derived oxidants in biological systems. Moreover, tyrosine nitration impacts protein structure and function, tyrosine kinase signal transduction cascades and protein turnover. Overall, the revi...
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Peroxynitrite, a stealthy biological oxidant
The Journal of biological chemistry, 2013Co-Authors: Rafael RadiAbstract:Peroxynitrite is the product of the Diffusion-Controlled Reaction of nitric oxide and superoxide radicals. Peroxynitrite, a reactive short-lived peroxide with a pKa of 6.8, is a good oxidant and nucleophile. It also yields secondary free radical intermediates such as nitrogen dioxide and carbonate radicals. Much of nitric oxide- and superoxide-dependent cytotoxicity resides on peroxynitrite, which affects mitochondrial function and triggers cell death via oxidation and nitration Reactions. Peroxynitrite is an endogenous toxicant but is also a cytotoxic effector against invading pathogens. The biological chemistry of peroxynitrite is modulated by endogenous antioxidant mechanisms and neutralized by synthetic compounds with peroxynitrite-scavenging capacity.
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peroxynitrite biochemistry pathophysiology and development of therapeutics
Nature Reviews Drug Discovery, 2007Co-Authors: Harry Ischiropoulos, Csaba Szabo, Rafael RadiAbstract:Peroxynitrite--the product of the Diffusion-Controlled Reaction of nitric oxide with superoxide radical--is a short-lived oxidant species that is a potent inducer of cell death. Conditions in which the Reaction products of peroxynitrite have been detected and in which pharmacological inhibition of its formation or its decomposition have been shown to be of benefit include vascular diseases, ischaemia-reperfusion injury, circulatory shock, inflammation, pain and neurodegeneration. In this Review, we first discuss the biochemistry and pathophysiology of peroxynitrite and then focus on pharmacological strategies to attenuate the toxic effects of peroxynitrite. These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.
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nitric oxide oxidants and protein tyrosine nitration
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Rafael RadiAbstract:The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions of (.)NO to oxidative and potentially pathogenic pathways. Tyrosine nitration is mediated by reactive nitrogen species such as peroxynitrite anion (ONOO(-)) and nitrogen dioxide ((.)NO2), formed as secondary products of (.)NO metabolism in the presence of oxidants including superoxide radicals (O2(.-)), hydrogen peroxide (H2O2), and transition metal centers. The precise interplay between (.)NO and oxidants and the identification of the proximal intermediate(s) responsible for nitration in vivo have been under controversy. Despite the capacity of peroxynitrite to mediate tyrosine nitration in vitro, its role on nitration in vivo has been questioned, and alternative pathways, including the nitrite/H2O2/hemeperoxidase and transition metal-dependent mechanisms, have been proposed. A balanced analysis of existing evidence indicates that (i) different nitration pathways can contribute to tyrosine nitration in vivo, and (ii) most, if not all, nitration pathways involve free radical biochemistry with carbonate radicals (CO3(.-)) and/or oxo-metal complexes oxidizing tyrosine to tyrosyl radical followed by the Diffusion-Controlled Reaction with (.)NO2 to yield 3-nitrotyrosine. Although protein tyrosine nitration is a low-yield process in vivo, 3-nitrotyrosine has been revealed as a relevant biomarker of (.)NO-dependent oxidative stress; additionally, site-specific nitration focused on particular protein tyrosines may result in modification of function and promote a biological effect. Tissue distribution and quantitation of protein 3-nitrotyrosine, recognition of the predominant nitration pathways and individual identification of nitrated proteins in disease states open new avenues for the understanding and treatment of human pathologies.
Thomas F Fassler - One of the best experts on this subject based on the ideXlab platform.
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zintl phases k4 xnaxsi4 1 x 2 2 and k7nasi8 synthesis crystal structures and solid state nmr spectroscopic investigations
European Journal of Inorganic Chemistry, 2016Co-Authors: Lavinia M Scherf, Oliver Pecher, Kent J Griffith, Frank Haarmann, Clare P Grey, Thomas F FasslerAbstract:The Zintl phases K4–xNaxSi4 (1 ≤ x ≤ 2.2) and K7NaSi8 are the first representatives of the K–Na–Si system, and both contain tetrahedral [Si4]4– clusters and a charge-balancing number of K+ and Na+ cations. All phases of K4–xNaxSi4 (1 ≤ x ≤ 2.2) crystallize in a new structure type with space group P21/n, as determined by single-crystal X-ray diffraction analysis of the parent phase K3NaSi4. Rietveld refinement of the X-ray diffraction data showed that the solid solutions follow Vegard's rule. K7NaSi8 can only be synthesized by Diffusion-Controlled Reaction of binary precursors and is isostructural with known A7A′T8 (A = Na–Cs; A′ = Li, Na; T = Si, Ge) phases. A combination of solid-state NMR investigations and quantum mechanical calculations served to show the anisotropic chemical bonding behavior of all the atoms in K7NaSi8, which is additionally compared with the related phases A7NaSi8 (A = Rb, Cs).
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Zintl Phases K4–xNaxSi4(1 ≤ x ≤ 2.2) and K7NaSi8: Synthesis, Crystal Structures, and Solid-State NMR Spectroscopic Investigations
'Organisation for Economic Co-Operation and Development (OECD)', 2016Co-Authors: Lm Scherf, Pecher Oliver, Griffith Kent, Haarmann F, Grey Clare, Thomas F FasslerAbstract:The Zintl phases K₄₋ₓNaₓSi₄ (1 ≤ x ≤ 2.2) and K₇NaSi₈ are the first representatives of the K–Na–Si system, and both contain tetrahedral [Si₄]⁴⁻ clusters and a charge-balancing number of K⁺ and Na⁺ cations. All phases of K₄₋ₓNaₓSi₄ (1 ≤ x ≤ 2.2) crystallize in a new structure type with space group P2₁/n, as determined by single-crystal X-ray diffraction analysis of the parent phase K₃NaSi₄. Rietveld refinement of the X-ray diffraction data showed that the solid solutions follow Vegard's rule. K₇NaSi₈ can only be synthesized by Diffusion-Controlled Reaction of binary precursors and is isostructural with known A₇A′T₈ (A = Na–Cs; A′ = Li, Na; T = Si, Ge) phases. A combination of solid-state NMR investigations and quantum mechanical calculations served to show the anisotropic chemical bonding behavior of all the atoms in K₇NaSi₈, which is additionally compared with the related phases A₇NaSi₈ (A = Rb, Cs).We gratefully acknowledge fruitful discussions with Dr. Rachel N. Kerber (Cambridge). L. M. S. is grateful for financial support by the Fonds der Chemischen Industrie and a fellowship from the Studienstiftung des deutschen Volkes. This work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. K. J. G. thanks the Winston Churchill Foundation of the United States and the Herchel Smith Scholarship for financial support
Lavinia M Scherf - One of the best experts on this subject based on the ideXlab platform.
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zintl phases k4 xnaxsi4 1 x 2 2 and k7nasi8 synthesis crystal structures and solid state nmr spectroscopic investigations
European Journal of Inorganic Chemistry, 2016Co-Authors: Lavinia M Scherf, Oliver Pecher, Kent J Griffith, Frank Haarmann, Clare P Grey, Thomas F FasslerAbstract:The Zintl phases K4–xNaxSi4 (1 ≤ x ≤ 2.2) and K7NaSi8 are the first representatives of the K–Na–Si system, and both contain tetrahedral [Si4]4– clusters and a charge-balancing number of K+ and Na+ cations. All phases of K4–xNaxSi4 (1 ≤ x ≤ 2.2) crystallize in a new structure type with space group P21/n, as determined by single-crystal X-ray diffraction analysis of the parent phase K3NaSi4. Rietveld refinement of the X-ray diffraction data showed that the solid solutions follow Vegard's rule. K7NaSi8 can only be synthesized by Diffusion-Controlled Reaction of binary precursors and is isostructural with known A7A′T8 (A = Na–Cs; A′ = Li, Na; T = Si, Ge) phases. A combination of solid-state NMR investigations and quantum mechanical calculations served to show the anisotropic chemical bonding behavior of all the atoms in K7NaSi8, which is additionally compared with the related phases A7NaSi8 (A = Rb, Cs).
Yi Zhang - One of the best experts on this subject based on the ideXlab platform.
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indirect electrochemical cr iii oxidation in koh solutions at an au electrode the role of oxygen reduction Reaction
Journal of Physical Chemistry B, 2012Co-Authors: Wei Jin, Shili Zheng, Yi Zhang, Michael S Moats, J D MillerAbstract:The indirect electro-oxidation of Cr(III) by in situ generated superoxide at a gold electrode has been investigated in KOH solutions using cyclic voltammetry and UV-vis spectroscopy. It is observed that the indirect Cr(III) oxidation behavior is substantially affected by the media pH and there is a pH-modulated oxygen reduction Reaction (ORR) process to generate reactive oxygen species which promotes Cr(III) oxidation. The ORR in KOH solutions is attributed to a quasi-reversible Diffusion-Controlled Reaction. In dilute KOH solution (0.2 M), 4e reduction occurs and no reactive oxygen species are generated for the indirect Cr(III) oxidation. Moreover, Cr(III) oxidation is inhibited due to competition for the electrode active sites. As the alkaline concentration increases (3.0 M), the protonation of superoxide is greatly suppressed, and thus, le ORR to generate superoxide is observed. This change in mechanism facilitates the indirect Cr(III) oxidation through the superoxide as a mediator to oxidize Cr(III) to Cr(IV), which is the rate-determining step of Cr(III) oxidation to Cr(VI).
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comparison of the oxygen reduction Reaction between naoh and koh solutions on a pt electrode the electrolyte dependent effect
Journal of Physical Chemistry B, 2010Co-Authors: Wei Jin, Shili Zheng, Yi ZhangAbstract:The oxygen reduction Reaction (ORR) on a polycrystalline Pt surface was studied using cyclic voltammetry techniques, and the influence of Reaction media on the ORR is examined by comparing the ORR in NaOH and KOH solutions with concentration ranging from 0.5 to 14 M at 298 K. The results show that, in NaOH and KOH solutions, the ORR, a quasi-reversible Diffusion-Controlled Reaction, is largely dependent on the electrolyte conditions, and KOH solutions are superior to NaOH solutions for the ORR process in both thermodynamic and kinetic consideration. As the alkaline concentration increases, the ORR performance frustrates, and the protonation of superoxide is suppressed; thus, the ORR shifts from a 2e reduction pathway to a 1e reduction pathway in both solutions.
Wei Jin - One of the best experts on this subject based on the ideXlab platform.
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indirect electrochemical cr iii oxidation in koh solutions at an au electrode the role of oxygen reduction Reaction
Journal of Physical Chemistry B, 2012Co-Authors: Wei Jin, Shili Zheng, Yi Zhang, Michael S Moats, J D MillerAbstract:The indirect electro-oxidation of Cr(III) by in situ generated superoxide at a gold electrode has been investigated in KOH solutions using cyclic voltammetry and UV-vis spectroscopy. It is observed that the indirect Cr(III) oxidation behavior is substantially affected by the media pH and there is a pH-modulated oxygen reduction Reaction (ORR) process to generate reactive oxygen species which promotes Cr(III) oxidation. The ORR in KOH solutions is attributed to a quasi-reversible Diffusion-Controlled Reaction. In dilute KOH solution (0.2 M), 4e reduction occurs and no reactive oxygen species are generated for the indirect Cr(III) oxidation. Moreover, Cr(III) oxidation is inhibited due to competition for the electrode active sites. As the alkaline concentration increases (3.0 M), the protonation of superoxide is greatly suppressed, and thus, le ORR to generate superoxide is observed. This change in mechanism facilitates the indirect Cr(III) oxidation through the superoxide as a mediator to oxidize Cr(III) to Cr(IV), which is the rate-determining step of Cr(III) oxidation to Cr(VI).
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comparison of the oxygen reduction Reaction between naoh and koh solutions on a pt electrode the electrolyte dependent effect
Journal of Physical Chemistry B, 2010Co-Authors: Wei Jin, Shili Zheng, Yi ZhangAbstract:The oxygen reduction Reaction (ORR) on a polycrystalline Pt surface was studied using cyclic voltammetry techniques, and the influence of Reaction media on the ORR is examined by comparing the ORR in NaOH and KOH solutions with concentration ranging from 0.5 to 14 M at 298 K. The results show that, in NaOH and KOH solutions, the ORR, a quasi-reversible Diffusion-Controlled Reaction, is largely dependent on the electrolyte conditions, and KOH solutions are superior to NaOH solutions for the ORR process in both thermodynamic and kinetic consideration. As the alkaline concentration increases, the ORR performance frustrates, and the protonation of superoxide is suppressed; thus, the ORR shifts from a 2e reduction pathway to a 1e reduction pathway in both solutions.