title: Comparison of the chemical reactivity of synthetic peroxynitrite with that of the autoxidation products of nitroxyl or its anion.
abstract: Donors of nitroxyl (HNO) exhibit pharmacological properties that are potentially favorable for treatment of a variety of diseases. To fully evaluate the pharmacological utility of HNO, it is therefore important to understand its chemistry, particularly involvement in deleterious biological reactions. Of particular note is the cytotoxic species formed from HNO autoxidation that is capable of inducing double strand DNA breaks. The identity of this species remains elusive, but a conceivable product is peroxynitrous acid. However, chemical comparison studies have demonstrated that HNO autoxidation leads to a unique reactive nitrogen oxide species to that of synthetic peroxynitrite. Here, we extend the analysis to include a new preparation of peroxynitrite formed via autoxidation of nitroxyl anion (NO(-)). Both peroxynitrite preparations exhibited similar chemical profiles, although autoxidation of NO(-) provided a more reliable sample of peroxynitrite. Furthermore, the observed dissimilarities to the HNO donor Angeli's salt substantiate that HNO autoxidation produces a unique intermediate from peroxynitrite.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA; Department of Chemistry, Mindanao State University - Iligan Institute of Technology, Iligan 9200, Philippines.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Jorolan
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Buttitta
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cheah
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. Electronic address: kmiranda@email.arizona.edu.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
mesh_terms: D000838:Anions / Q000737:chemistry*; D019817:Benzoic Acid; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D009566:Nitrates; D009569:Nitric Oxide; D009573:Nitrites; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen; D030421:Peroxynitrous Acid / Q000737:chemistry*; D012235:Rhodamines
chemical_list: D000838:Anions; D005456:Fluorescent Dyes; D009566:Nitrates; D009573:Nitrites; D009589:Nitrogen Oxides; D012235:Rhodamines; C058319:dihydrorhodamine 123; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D019817:Benzoic Acid; C039900:nitroxyl; D010100:Oxygen
keywords: Angeli's salt; Autoxidation; IPA/NO; Nitric oxide; Nitroxyl; Peroxynitrite