title: Perturbing peptide cation-radical electronic states by thioxoamide groups: formation, dissociations, and energetics of thioxopeptide cation-radicals.
abstract: 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-MS(5). 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-C(α) 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.
authors: Department of Chemistry, Bagley Hall, Box 351700, University of Washington, Seattle, Washington 98195-1700, USA.
authors: Magdalena
authors: M
authors: Zimnicka
authors: Thomas W
authors: TW
authors: Chung
authors: Christopher L
authors: CL
authors: Moss
authors: František
authors: F
authors: Tureček
mesh_terms: D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D004583:Electrons; D005609:Free Radicals / Q000138:chemical synthesis / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D011789:Quantum Theory; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013997:Time Factors
chemical_list: D002412:Cations; D004151:Dipeptides; D005609:Free Radicals; D011725:Pyridines; D013438:Sulfhydryl Compounds; C034960:oxoamide