title: HNO and NO release from a primary amine-based diazeniumdiolate as a function of pH.
abstract: The growing evidence that nitroxyl (HNO) has a rich pharmacological potential that differs from that of nitric oxide (NO) has intensified interest in HNO donors. Recently, the diazeniumdiolate (NONOate) based on isopropylamine (IPA/NO; Na[(CH(3))(2)CHNH(N(O)NO)]) was demonstrated to function under physiological conditions as an organic analogue to the commonly used HNO donor Angeli's salt (Na(2)N(2)O(3)). The decomposition mechanism of Angeli's salt is dependent on pH, with transition from an HNO to an NO donor occurring abruptly near pH 3. Here, pH is shown to also affect product formation from IPA/NO. Chemical analysis of HNO and NO production led to refinement of an earlier, quantum mechanically based prediction of the pH-dependent decomposition mechanisms of primary amine NONOates such as IPA/NO. Under basic conditions, the amine proton of IPA/NO is able to initiate decomposition to HNO by tautomerization to the nitroso nitrogen (N(2)). At lower pH, protonation activates a competing pathway to NO production. At pH 8, the donor properties of IPA/NO and Angeli's salt are demonstrated to be comparable, suggesting that at or above this pH, IPA/NO is primarily an HNO donor. Below pH 5, NO is the major product, while IPA/NO functions as a dual donor of HNO and NO at intermediate pH. This pH-dependent variability in product formation may prove useful in examination of the chemistry of NO and HNO. Furthermore, primary amine NONOates may serve as a tunable class of nitrogen oxide donor.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Salmon
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Torres de Holding
authors.forename: Lynta
authors.initials: L
authors.lastname: Thomas
authors.forename: Kyle V
authors.initials: KV
authors.lastname: Peterson
authors.forename: Gens P
authors.initials: GP
authors.lastname: Goodman
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Saavedra
authors.forename: Aloka
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Keith M
authors.initials: KM
authors.lastname: Davies
authors.forename: Larry K
authors.initials: LK
authors.lastname: Keefer
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
mesh_terms: D000588:Amines / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009589:Nitrogen Oxides / Q000737:chemistry*
chemical_list: D000588:Amines; D001391:Azo Compounds; D009589:Nitrogen Oxides; C452539:diazeniumdiolate; C039900:nitroxyl