title: Intramolecular hydrogen atom migration along the backbone of cationic and neutral radical tripeptides and subsequent radical-induced dissociations.
abstract: Dissociation of peptide radical ions involves competition between charge-induced and radical-induced reactions that can be preceded by isomerization. The isomeric radical cations of the peptide methyl ester [G˙GR-OMe](+) and [GG˙R-OMe](+) provide very similar collision-induced dissociation (CID) spectra, suggesting that isomerization occurs prior to fragmentation. They undergo characteristic radical-induced bond cleavage of the peptide N-terminal amide bond resulting in the y2(+) ion, and of the arginine side-chain's Cα-Cβ bond giving protonated allylguanidine {[CH2[double bond, length as m-dash]CHCH2NHC(NH2)2](+), m/z 100}. The absence of a y2(+) fragment ion in the CID of the radical cationic tripeptide [ACH3G˙R](+) and of an m/z 100 ion in the spectrum of [G˙ACH3R](+) (where ACH3 is an α-aminoisobutyric acid residue, which cannot form an α-carbon-centered radical through hydrogen atom transfer) establishes the importance of hydrogen atom migration along the peptide backbone prior to specific radical-induced fragmentations. Herein we use density functional theory (DFT) at the B3LYP/6-31++G(d,p) level to evaluate the barriers for interconversion between the α-carbon-centered radicals and for dissociation. The radical cations [G˙GR](+) and [GG˙R](+) have their radicals located on the α-carbon atoms of the peptide backbone and their charge densities largely sequestered on the guanidine groups of the side-chain of arginine residues. This is in contrast to the isomeric radical cations of [GGG]˙(+), in which the charge resides necessarily on the peptide backbone. The lower charge densities on the backbones of [G˙GR](+) and [GG˙R](+) result in greater structural flexibility, decreasing the barrier for interconversion between these α-carbon-centered radicals to 36.2 kcal mol(-1) (cf. 44.7 kcal mol(-1) for [GGG]˙(+)). The total absence of charge, assessed by examining intramolecular hydrogen atom transfers among the three α-carbon centers of the isomeric neutral α-carbon-centered triglycine radicals [GGG-H]˙, leads to an additional but slight reduction in enthalpy, to approximately 34 kcal mol(-1).
authors.affiliation: Department of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele Street, Toronto, Ontario, CanadaM3J 1P3. ach@yorku.ca.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Minjie
authors.initials: M
authors.lastname: Xu
authors.forename: Quan
authors.initials: Q
authors.lastname: Quan
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
authors.forename: Alan C
authors.initials: AC
authors.lastname: Hopkinson
authors.forename: Ivan K
authors.initials: IK
authors.lastname: Chu
mesh_terms: D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D007536:Isomerism; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D011789:Quantum Theory
chemical_list: D005609:Free Radicals; D009842:Oligopeptides; D006859:Hydrogen; C035647:glycyl-glycyl-glycine