Hydrogen atom transfer in metal ion complexes of the glutathione thiyl radical

Abstract

Isomerization of the glutathione thiyl radical via hydrogen atom transfer (HAT) in its complexes with various singly and doubly charged metal ions was studied both experimentally and computationally. The glutathione thiyl radical/metal ion complexes were generated in a quadrupole ion trap mass spectrometer via collision-induced dissociation of S-nitrosoglutathione cationized by the metal ion of interest. The degree of HAT was monitored by gas-phase ion-molecule reactions of these complexes with nitric oxide – the initially formed thiyl radical species were shown previously to be reactive toward NO while the α-carbon (Cα) radicals were not. It was found that group IA metal ions facilitate HAT in the order K+>Na+>Li+>H+. This correlates well with the order of relative stability of the resulting Cα species determined by density functional theory (DFT) calculations. Conversely, the glutathione thiyl radicals complexed by three different doubly-charged metal ions (Mg2+, Zn2+ or Ni2+) did not undergo HAT, thereby remaining the S-based radical species. This was rationalized in terms of the substantially smaller thermodynamic benefit of HAT in the case of Mg2+and Zn2+ and even the endothermicity of this process for Ni2+, as predicted by the DFT calculations. Additionally, for the glutathione radical/Ni2+ complex a possibility of iminol-type binding (as opposed to the “classical” keto form) to the metal ion was investigated computationally. It was found that the iminol structures are lower in energy than the keto ones, similar to the situation in the even-electron peptide/Ni2+ complexes.