Cysteine radical cation: A distonic structure probed by gas phase IR spectroscopy

Abstract

The interest in the radical cations of amino acids is twofold. On the one hand, these species are relevant in enzymatic catalysis and in oxidative damage of proteins. On the other hand, as constituents of peptides and proteins, they aid the mass spectrometric characterization of these biomolecules, yielding diagnostic fragmentation patterns and providing complementary information with respect to the one obtained from even electron ions. The cysteine radical cation has been obtained by S-NO bond cleavage of protonated S-nitrosocysteine and thoroughly characterized by IRMPD spectroscopy, both in the 1000-2000 cm(-1) range (the highly structurally diagnostic, so-called 'fingerprint' range) and in the 2900-3700 cm(-1) spectral range, encompassing O-H and N-H stretching vibrations. In this way the distonic structure in which the charge is on the NH(3) group and the spin is on the sulfur atom is unambiguously demonstrated. This tautomer is a local minimum on the potential energy surface, at 29.7 kJ mol(-1) with respect to the most stable tautomer, a captodative structure allowing extensive delocalization of charge and spin.

The Radical Ion Chemistry of S-Nitrosylated Peptides

“…Both Zhao et al [36] and Ryzhov et al [22], calculated that the most stable structure was the result of hydrogen atom transfer from the α-carbon giving an α-radical stabilized by the captodative effect [37]. Nevertheless, gas-phase IR spectroscopy by Fornarini and co-workers revealed the long-lived distonic structure of the radical [28]. More recent work by Ryzhov and co-workers [27] suggests that radical migration to the α-carbon does occur.…”

“…• NO neutral loss is observed following CID of Snitrosopeptides [5,22,[26][27][28], which might suggest a thermal process is occurring; however, no loss of + ions were observed when the energy of the electrons was reduced (Supplemental Figure 3).…”

Structure and Reactivity of theN-Acetyl-Cysteine Radical Cation and Anion: Does Radical Migration Occur?

“…An emerging method for determining the structure of these radical ions is through infrared multiple photon dissociation (IRMPD) spectroscopy. Since the first study on the structure of histidine radical cation [33], two other studies were performed on the cysteine radical cation [34] and its methyl ester [35]. Theoretical calculations have also been actively employed [36].…”

S-to-αC Radical Migration in the Radical Cations of Gly-Cys and Cys-Gly

“…In contrast, when randomly generated under conditions of oxidative stress, radical generation can be destructive to proteins [7][8][9][10][11][12], ultimately leading to loss of function. The S based thiyl radicals of the side chains of cysteine are one class of protein radicals that have attracted considerable recent attention through studies of model systems in both the condensed [12] and gas phases [13][14][15]. Of particular interest have been the structural requirements for intramolecular hydrogen atom transfer (HAT) from the α-carbon position to the sulfur in peptide thiyl radicals, which is slightly exothermic because of the enhanced stability of peptide backbone radicals, particularly those located at the α-carbon of glycine [11].…”