Nitroxyl (HNO) reacts with molecular oxygen and forms peroxynitrite at physiological pH. Biological Implications.
Nitroxyl (HNO), the protonated one-electron reduction product of NO, remains an enigmatic reactive nitrogen species. Its chemical reactivity and biological activity are still not completely understood. HNO donors show biological effects different from NO donors. Although HNO reactivity with molecular oxygen is described in the literature, the product of this reaction has not yet been unambiguously identified. Here we report that the decomposition of HNO donors under aerobic conditions in aqueous solutions at physiological pH leads to the formation of peroxynitrite (ONOO(-)) as a major intermediate. We have specifically detected and quantified ONOO(-) with the aid of boronate probes, e.g. coumarin-7-boronic acid or 4-boronobenzyl derivative of fluorescein methyl ester. In addition to the major phenolic products, peroxynitrite-specific minor products of oxidation of boronate probes were detected under these conditions. Using the competition kinetics method and a set of HNO scavengers, the value of the second order rate constant of the HNO reaction with oxygen (k = 1.8 × 10(4) m(-1) s(-1)) was determined. The rate constant (k = 2 × 10(4) m(-1) s(-1)) was also determined using kinetic simulations. The kinetic parameters of the reactions of HNO with selected thiols, including cysteine, dithiothreitol, N-acetylcysteine, captopril, bovine and human serum albumins, and hydrogen sulfide, are reported. Biological and cardiovascular implications of nitroxyl reactions are discussed.
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and.
Renata
R
Smulik
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and.
Dawid
D
Dębski
the Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
Jacek
J
Zielonka
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and.
Bartosz
B
Michałowski
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and.
Jan
J
Adamus
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and.
Andrzej
A
Marcinek
the Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 balarama@mcw.edu.
Balaraman
B
Kalyanaraman
From the Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland and adam.sikora@p.lodz.pl.
Adam
A
Sikora
D000111:Acetylcysteine / Q000737:chemistry; D000465:Algorithms; D000818:Animals; D001896:Boron Compounds / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D002216:Captopril / Q000737:chemistry; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D008956:Models, Chemical; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D030421:Peroxynitrous Acid / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000737:chemistry
D001896:Boron Compounds; D001897:Boronic Acids; D003374:Coumarins; D009589:Nitrogen Oxides; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D030421:Peroxynitrous Acid; D002216:Captopril; C039900:nitroxyl; D003545:Cysteine; D010100:Oxygen; D004229:Dithiothreitol; D000111:Acetylcysteine; D006862:Hydrogen Sulfide
Angeli's Salt; Boronate Probes; Cardioprotection; Cardiovascular; Ischemia; Nitric Oxide; Nitroxyl; Oxidative Stress; Peroxynitrite; Vascular