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Perturbing Peptide Cation-Radical Electronic States by Thioxoamide Groups: Formation, Dissociations, and Energetics of Thioxopeptide Cation-Radicals

2012; American Chemical Society; Volume: 117; Issue: 6 Linguagem: Inglês

10.1021/jp305865q

1520-5215

Magdalena Zimnicka, Thomas W. Chung, Christopher L. Moss, František Tureček,

Radical Photochemical Reactions

Thioxodipeptides Gly-thio-Lys (GtK), Ala-thio-Lys (AtK), and Ala-thio-Arg (AtR) in which the amide group has been modified to a thioxoamide were made into dications by electrospray ionization and converted to cation-radicals, (GtK + 2H)+•, (AtK + 2H)+•, and (AtR + 2H)+•, by electron transfer dissociation (ETD) tandem mass spectrometry using fluoranthene anion-radical as an electron donor. The common and dominant dissociation of these cation-radicals was the loss of a hydrogen atom. The dissociation products were characterized by collision-induced dissociation (CID) multistage tandem mass spectrometry up to CID-MS5. The ground electronic states of several (GtK + 2H)+•, (AtK + 2H)+•, and (AtR + 2H)+• conformers were explored by extensive ab initio and density functional theory calculations of the potential energy surface. In silico electron transfer to the precursor dications, (GtK + 2H)2+, (AtK + 2H)2+, and (AtR + 2H)2+, formed zwitterionic intermediates containing thioenol anion-radical and ammonium cation groups that were local energy minima on the potential energy surface of the ground electronic state. The zwitterions underwent facile isomerization by N-terminal ammonium proton migration to the thioenol anion-radical group forming aminothioketyl intermediates. Combined potential energy mapping and RRKM calculations of dissociation rate constants identified N–Cα bond cleavages as the most favorable dissociation pathways, in a stark contrast to the experimental results. This discrepancy is interpreted as being due to the population upon electron transfer of low-lying excited electronic states that promote loss of hydrogen atoms. For (GtK + 2H)+•, these excited states were characterized by time-dependent density functional theory as A–C states that had large components of Rydberg-like 3s molecular orbitals at the N-terminal and lysine ammonium groups that are conducive to hydrogen atom loss.