Structure and Reactivity of the Glutathione Radical Cation: Radical Rearrangement from the Cysteine Sulfur to the Glutamic Acid α-Carbon Atom

• Published in: ChemPlusChem (Weinheim, Germany) Germany), 2013-09, Vol.78 (9), p.970-978
• Main Authors: Osburn, Sandra, Berden, Giel, Oomens, Jos, Gulyuz, Kerim, Polfer, Nick C., O'Hair, Richard A. J., Ryzhov, Victor
• Format: Article
• Language: English
• Subjects: glutathione; ion-molecule reactions; IR spectroscopy; radical ions; rearrangement
• ISSN: 2192-6506; 2192-6506
• DOI: 10.1002/cplu.201300057

A gas‐phase radical rearrangement through intramolecular hydrogen‐atom transfer (HAT) was studied in the glutathione radical cation, [γ‐ECG]+., which was generated by a homolytic cleavage of the protonated S‐nitrosoglutathione. Ion–molecule reactions suggested that the radical migrates from the original sulfur position to one of the α‐carbon atoms. Experiments on the radical cations of dipeptides derived from the glutathione sequence, [γ‐EC]+. and [CG]+., pointed to the glutamic acid α‐carbon atom as the most likely site of the radical migration. Infrared multiple‐photon dissociation (IRMPD) spectroscopy was employed to generate complementary information. IRMPD of [γ‐ECG]+. in the approximately 1000–1800 cm−1 region was inconclusive owing to the relatively broad, overlapping absorption bands. However, the IRMPD spectrum of [γ‐EC]+. in this region was consistent with the radical migrating from the sulfur to the α‐carbon atom of glutamic acid. IRMPD in the 2800–3700 cm−1 region performed on [γ‐ECG]+. is consistent with a mixture of both the original sulfur‐based radical and the resulting glutamic acid α‐carbon‐based species. Comparisons are made with previously published condensed and gas‐phase studies on intramolecular HAT in glutathione. Totally radical: Gas‐phase ion–molecule reactions were used to observe a radical rearrangement in the radical cation of glutathione (see scheme). This rearrangement proceeded from sulfur to the glutamic acid α‐carbon atom, which was confirmed by infrared multiple photon dissociation (IRMPD) spectroscopy in two different IR regions (1000–1800 and 2800–3700 cm−1) and DFT calculations.