Reactive nitrogen species reactivities with nitrones: theoretical and experimental studies
Kevin M Nash1, Antal Rockenbauer, Frederick A Villamena
1Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Chemical Research in Toxicology
|July 11, 2012
Summary
Nitrone spin traps effectively detect damaging reactive nitrogen species (RNS) using electron paramagnetic resonance (EPR) spectroscopy. These spin traps also show potential as antioxidants against RNS-mediated oxidative damage in biological systems.
Area of Science:
- Biochemistry and Molecular Biology
- Chemical Biology
- Spectroscopy
Background:
- Reactive nitrogen species (RNS) are highly damaging in biological systems, causing oxidative, nitrosylative, and nitrative modifications to biomolecules.
- Nitrone spin traps are established reagents for detecting free radicals via electron paramagnetic resonance (EPR) spectroscopy and possess pharmacological antioxidant properties.
Purpose of the Study:
- To investigate the reactivity of cyclic nitrones, specifically 5,5-dimethylpyrroline N-oxide (DMPO), with various reactive nitrogen species (RNS).
- To elucidate the reaction mechanisms and thermochemistry of nitrone-RNS interactions using computational methods and EPR spectroscopy.
- To explore the potential of nitrone spin traps as both detection probes and therapeutic agents against RNS-induced oxidative stress.
Main Methods:
- Electron paramagnetic resonance (EPR) spectroscopy was employed to study the spin trapping of RNS by cyclic nitrones.
- Computational chemistry calculations (PCM(water)/B3LYP/6-31+G**//B3LYP/6-31G*) were performed to determine thermochemistries and hyperfine coupling constants (hfscs) of addition products.
- Mass spectrometry was used in conjunction with EPR spin trapping to investigate a broader range of RNS, including azide, nitrogen trioxide, amino radicals, and nitroxyl.
Main Results:
- The study successfully demonstrated the spin trapping of nitrogen dioxide ((•)NO(2)), peroxynitrite (ONOO(-)), and nitrosoperoxycarbonate (ONOOCO(2)(-)) by DMPO using EPR.
- Computational analysis provided insights into the electronic structure and stability of the nitrone-RNS adducts, rationalizing the observed EPR spectra.
- Various nitrone spin traps, including DMPO and its derivatives, were shown to react with both radical and nonradical RNS, confirming their versatility.
Conclusions:
- Nitrone spin traps are effective tools for the detection and characterization of reactive nitrogen species (RNS) using EPR spectroscopy.
- The reactivity profile and computational data support the role of nitrones in scavenging RNS, highlighting their potential as antioxidants.
- This research validates nitrone spin traps as valuable probes and potential therapeutic agents for mitigating RNS-mediated oxidative damage.
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