title: Synthesis and spin-trapping properties of a trifluoromethyl analogue of DMPO: 5-methyl-5-trifluoromethyl-1-pyrroline N-oxide (5-TFDMPO).
abstract: The 5-diethoxyphosphonyl-5-methyl-1-pyrroline N-oxide superoxide spin adduct (DEPMPO-OOH) is much more persistent (about 15 times) than the 5,5-dimethyl-1-pyrroline N-oxide superoxide spin adduct (DMPO-OOH). The diethoxyphosphonyl group is bulkier than the methyl group and its electron-withdrawing effect is much stronger. These two factors could play a role in explaining the different half-lifetimes of DMPO-OOH and DEPMPO-OOH. The trifluoromethyl and the diethoxyphosphonyl groups show similar electron-withdrawing effects but have different sizes. We have thus synthesized and studied 5-methyl-5-trifluoromethyl-1-pyrroline N-oxide (5-TFDMPO), a new trifluoromethyl analogue of DMPO, to compare its spin-trapping performance with those of DMPO and DEPMPO. 5-TFDMPO was prepared in a five-step sequence by means of the Zn/AcOH reductive cyclization of 5,5,5-trifluoro-4-methyl-4-nitropentanal, and the geometry of the molecule was estimated by using DFT calculations. The spin-trapping properties were investigated both in toluene and in aqueous buffer solutions for oxygen-, sulfur-, and carbon-centered radicals. All the spin adducts exhibit slightly different fluorine hyperfine coupling constants, thereby suggesting a hindered rotation of the trifluoromethyl group, which was confirmed by variable-temperature EPR studies and DFT calculations. In phosphate buffer at pH 7.4, the half-life of 5-TFDMPOOOH is about three times shorter than for DEPMPO-OOH and five times longer than for DMPO-OOH. Our results suggest that the stabilization of the superoxide adducts comes from a delicate balance between steric, electronic, and hydrogen-bonding effects that involve the β group, the hydroperoxyl moiety, and the nitroxide.
authors.affiliation: Aix-Marseille Université, CNRS UMR7273, Institut de Chimie Radicalaire (ICR), Case 521, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20 (France), Fax: (+33) 491-288-758.
authors.forename: Hakim
authors.initials: H
authors.lastname: Karoui
authors.forename: Céline
authors.initials: C
authors.lastname: Nsanzumuhire
authors.forename: François
authors.initials: F
authors.lastname: Le Moigne
authors.forename: Micael
authors.initials: M
authors.lastname: Hardy
authors.forename: Didier
authors.initials: D
authors.lastname: Siri
authors.forename: Etienne
authors.initials: E
authors.lastname: Derat
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.forename: Olivier
authors.initials: O
authors.lastname: Ouari
authors.forename: Paul
authors.initials: P
authors.lastname: Tordo
mesh_terms: D002244:Carbon / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D015394:Molecular Structure; D019097:Spin Trapping / Q000379:methods*; D013481:Superoxides / Q000737:chemistry*
chemical_list: D013481:Superoxides; D002244:Carbon
keywords: EPR spectroscopy; fluorinated ligands; radicals; spin trapping; substituent effects