Faculty Collaboration Database

Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection. Org Biomol Chem 2017 Aug 02;15(30):6358-6366

Date

07/18/2017

Pubmed ID

28715016

DOI

10.1039/c7ob00961e

Scopus ID

2-s2.0-85026838922 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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 ≈ 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO˙ adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 μM, 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-β-CD rim.

Author List

Poulhès F, Rizzato E, Bernasconi P, Rosas R, Viel S, Jicsinszky L, Rockenbauer A, Bardelang D, Siri D, Gaudel-Siri A, Karoui H, Hardy M, Ouari O

Author

Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Ascorbic Acid
Chemistry Techniques, Synthetic
Electron Spin Resonance Spectroscopy
Glutathione
Kinetics
Limit of Detection
Molecular Conformation
Molecular Dynamics Simulation
Nitrogen Oxides
Spin Labels
Superoxides
beta-Cyclodextrins