title: CyDEPMPOs: a class of stable cyclic DEPMPO derivatives with improved properties as mechanistic markers of stereoselective hydroxyl radical adduct formation in biological systems.
abstract: The cis/trans diastereoisomeric composition of hydroxyl radical adducts to chiral cyclic nitrones can be used to approach mechanisms of free radical formation in biological systems. Such determination is greatly simplified when both diastereoisomers have ESR spectra with at least two non-overlapping lines. To achieve this prerequisite, a series of DEPMPO-derived spin traps bearing one unsubstituted or alkyl-substituted 2-oxo-1,3,2-dioxaphosphorinane ring were synthesized and their structures were confirmed by X-ray diffraction, (1)H, (13)C and (31)P NMR. These CyDEPMPOs nitrones showed variable lipophilicities and LD(50) values on murine fibroblasts compatible with a safe use in biological spin trapping. All CyDEPMPOs formed persistent spin adducts with a series of free radicals, including superoxide and hydroxyl (i.e., CyDEPMPOs-OH) and the in vitro half-life times of these two latter were at least as extended as those of parent DEPMPO. Using four methods of CyDEPMPOs-OH formation, the cis-CyDEPMPOs-OH percentage was found significantly varied with substitution on the P-containing ring and, more interestingly, with the generating system.
authors.affiliation: Sondes Moléculaires en Biologie, Laboratoire Chimie Provence, CNRS UMR 6264, Universités d'Aix-Marseille, Centre Scientifique de Saint-Jérôme (Case 522), 13397 Marseille Cedex 20, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Gosset
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Clément
authors.forename: Marcel
authors.initials: M
authors.lastname: Culcasi
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.forename: Sylvia
authors.initials: S
authors.lastname: Pietri
mesh_terms: D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D017665:Hydroxyl Radical / Q000737:chemistry*; D007700:Kinetics; D008968:Molecular Conformation; D019097:Spin Trapping / Q000379:methods*; D013237:Stereoisomerism; D013481:Superoxides / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003497:Cyclic N-Oxides; D013481:Superoxides; C098505:5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide; D017665:Hydroxyl Radical