1. Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection
- Author
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Patrick Bernasconi, Egon Rizzato, Antal Rockenbauer, Didier Siri, Anouk Gaudel-Siri, Olivier Ouari, Roselyne Rosas, Stéphane Viel, Hakim Karoui, Micael Hardy, Laszlo Jicsinszky, David Bardelang, Florent Poulhès, Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Spectropôle - Aix Marseille Université (AMU SPEC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Cyclolab recherche et développement, PO Box 435, H-1525 Budapest, Hongrie, Institute of Materials and Environmental Chemistry [Budapest], Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Laboratoire Chimie Provence (LCP), Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
- Subjects
Nitroxide mediated radical polymerization ,Molecular Conformation ,Ascorbic Acid ,Chemistry Techniques, Synthetic ,Molecular Dynamics Simulation ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,in-vivo ,cyclic nitrone ,Adduct ,Nitrone ,law.invention ,metabolic stability ,chemistry.chemical_compound ,conjugate ,law ,Limit of Detection ,Superoxides ,Moiety ,[CHIM]Chemical Sciences ,Physical and Theoretical Chemistry ,epr ,Electron paramagnetic resonance ,Alkyl ,chemistry.chemical_classification ,Cyclodextrin ,radical adducts ,010405 organic chemistry ,Chemistry ,Superoxide ,Organic Chemistry ,beta-Cyclodextrins ,Electron Spin Resonance Spectroscopy ,Glutathione ,0104 chemical sciences ,Kinetics ,inclusion ,trapping properties ,resonance ,depmpo ,Nitrogen Oxides ,Spin Labels - Abstract
International audience; Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previously reported for CD-DEPMPO (t(1/2) approximate to 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO center dot adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 mu M, the new spin trap enables the reliable detection of superoxide by 1 scan at the position opposite to the corresponding spin trap without the CD moiety. The resistance of the spin adducts to a reduction process has been evaluated, and the superoxide spin adducts are sensitive to ascorbate and glutathione (GSH), but not to glutathione peroxidase/GSH, reflecting the exposed nature of the nitroxide moiety to the bulk solvent. To understand these results, 2D-ROESY NMR studies and molecular dynamics pointed to a shallow or surface self-inclusion of the nitrone spin traps and of nitroxide spin adducts presumably due to the high flexibility of the permethyl-beta-CD rim.
- Published
- 2017