title: Very stable superoxide radical adducts of 5-ethoxycarbonyl- 3,5-dimethyl-pyrroline N-oxide (3,5-EDPO) and its derivatives.
abstract: Oxygen radicals are involved in the onset of many diseases. Adequate spin traps are required for identification and localisation of free radical formation in biological systems. Superoxide spin adducts with half-lives up to 20 min at physiological pH have recently been reported to be formed from derivatives of the spin trap 5-ethoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO). This is a major improvement over DMPO (t(1/2) ca. 45 s), and even DEPMPO (t(1/2) ca. 14 min). In this study, an additional methyl group was introduced into position 3 or 4 of the pyrroline ring which greatly increases the stability of the respective superoxide spin adducts. In addition, the ethoxy group of EMPO was exchanged by either a propoxy- or an iso-propoxy group in order to test the influence of increasing lipophilic properties of the investigated spin traps. The structure of all compounds was confirmed by (1)H and (13)C-NMR with full signal assignment. In comparison with EMPO (t(1/2) ca. 8 min) or DEPMPO (t(1/2) ca. 14 min), the superoxide adducts of all novel spin traps were considerably higher (t(1/2) ca. 12-55 min). In addition, various other spin adducts obtained from oxygen-centered as well as carbon-centered radicals (e.g. derived from methanol or linoleic acid hydroperoxide) were also detected.
authors.affiliation: Research Institute of Biochemical Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Stolze
authors.forename: Natascha
authors.initials: N
authors.lastname: Rohr-Udilova
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenau
authors.forename: Roswitha
authors.initials: R
authors.lastname: Stadtmüller
authors.forename: Hans
authors.initials: H
authors.lastname: Nohl
mesh_terms: D002247:Carbon Isotopes; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000737:chemistry*; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis / Q000138:chemical synthesis*; D006207:Half-Life; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D011522:Protons; D011758:Pyrroles / Q000032:analysis / Q000138:chemical synthesis*; D013113:Spin Labels / Q000138:chemical synthesis*; D019097:Spin Trapping; D013237:Stereoisomerism; D013481:Superoxides / Q000737:chemistry*
chemical_list: D002247:Carbon Isotopes; D003497:Cyclic N-Oxides; D005609:Free Radicals; D011522:Protons; D011758:Pyrroles; D013113:Spin Labels; D013481:Superoxides; C013231:pyrroline