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

Abstract

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.

Cysteine Radical/Metal Ion Adducts: A Gas‐Phase Structural Elucidation and Reactivity Study

“…This type of behavior indicates that the sulfur radical structure isomerizes to a less reactive isomer: for instance, a C α radical that results in an isomeric mixture. We have previously seen this behavior with other sulfur‐based radical species, including the radical cations of glutathione and γGluCys . In this case, only about 25 % of the Cys radical/silver ion complex appears to have the reactive sulfur‐based radical structure.…”

“…In larger systems in which both the proton and hydrogen‐atom transfer steps are less hindered, barriers to isomerization are substantially lower. For instance, S‐based radical cations of dipeptides GlyCys, γ‐GluCys, and the tripeptide glutathione were found to undergo facile rearrangements into C α radical species …”

Unleashing radical sites in non‐covalent complexes: The case of the protonated S‐nitrosocysteine/18‐crown‐6 complex

“…Eqns. and ) whereas the α‐carbon is unreactive, leading to unique reactivity profiles when there is a mixture of radical sites since the radical abstraction reactions do not go to completion . This does not occur for the reaction shown in Fig.…”

“…(5) and (6)) whereas the α-carbon is unreactive, leading to unique reactivity profiles when there is a mixture of radical sites since the radical abstraction reactions do not go to completion. [21,23,24] This does not occur for the reaction shown in Fig. 3(a), where the presence of the 18-C-6 ring slows the reactivity down but does not stop it.…”

“…(5)) or an iodine atom(Eqn. (6)), [20][21][22][23][24] and here we have measured the rate constant of this reaction to be 1.03 × 10 -9 cm 3 molecule -1 s -1 , corresponding to an efficiency of 85%. The [CysS + H + (18-C-6)] •+ non-covalent complex undergoes the same types of reactions, but it reacts at an order of magnitude more slowly, with a rate constant of 7.6 × 10 -11 cm 3 molecule -1 s -1 , corresponding to an efficiency of 8%.…”