Histidine-Containing Radicals in the Gas Phase

Abstract

Radicals containing the histidine residue have been generated in the gas phase by femtosecond electron transfer to protonated histidine-N-methylamide (1H+), Nalpha-acetylhistidine-N-methylamide (2H+), Nalpha-glycylhistidine (3H+), and Nalpha-histidylglycine (4H+). Radicals generated by collisional electron transfer from dimethyldisulfide to ions 1H+ and 2H+ at 7 keV collision energies were found to dissociate completely on the microsecond time scale, as probed by reionization to cations. The main dissociations produced fragments from the imidazole side chain and the cleavage of the C(alpha)CO bond, whereas products of NCalpha bond cleavage were not observed. Electron transfer from gaseous potassium atoms to ions 3H+ and 4H+ at 2.97 keV collision energies not only caused backbone NCalpha bond dissociations but also furnished fractions of stable radicals that were detected after conversion to anions. Ion structures, ion-electron recombination energies, radical structures, electron affinities, and dissociation and transition-state energies were obtained by combined density functional theory and Møller-Plesset perturbational calculations (B3-PMP2) and basis sets ranging from 6-311+G(2d,p) to aug-cc-pVTZ. The Rice-Ramsperger-Kassel-Marcus theory was used to calculate rate constants on the B3-PMP2 potential energy surfaces to aid interpretation of the mass spectrometric data. The stability of Nalpha-histidylglycine-derived radicals is attributed to an exothermic isomerization in the imidazole ring, which is internally catalyzed by reversible proton transfer from the carboxyl group. The isomerization depends on the steric accessibility of the histidine side chain and the carboxyl group and involves a novel cation radical-COO salt-bridge intermediate.

Difference of Electron Capture and Transfer Dissociation Mass Spectrometry on Ni2+-, Cu2+-, and Zn2+-Polyhistidine Complexes in the Absence of Remote Protons

“…Electron attachment to the protonated histidine residue produces an imidazoline radical of the [1H,3H]-type, which undergoes an exothermic hydrogen radical rearrangement to form an isomeric radical having a [1H,2H]-type imidazoline group [24]. In the ETD mass spectrum, the intact electron-transfer product produces an intense signal owing to the high stability of the [1H,2H]-type imidazoline radical [25][26][27]. In contrast to ETD, ECD of a protonated histidine-containing peptide induces loss of a hydrogen radical via a [1H,2H]-type imidazoline radical, followed by the backbone dissociation of even-electron ions [28].…”

Gas-Phase Peptide Sulfinyl Radical Ions: Formation and Unimolecular Dissociation

“…Several groups have utilized both experimental approaches (i.e., ion/molecule reactions [14,15,27] and ion spectroscopy [43][44][45]) and theoretical calculations [21,[46][47][48][49] to investigate the structures of amino acid or small peptide radical ions. Radical ion chemistry, such as intramolecular radical migration [27,50] and competition between charge-and radical-directed dissociation upon collisional activation [49][50][51] have also been explored with different chemical systems.…”

Tunable Charge Tags for Electron-Based Methods of Peptide Sequencing: Design and Applications

“…In general, these are greater than the intrinsic recombination energies of charged groups in amino acid and peptide ions, which range between 2.8 and 3.7 eV for RE a (Table 1) [38][39][40][41][42][43][44] and depend on the charge internal solvation and thus the ion secondary structure. The RE for the AQC group indicate that electron attachment to doubly charged AQCderivatized peptides should form a cation-radical in which the radical site is in the quinoline ring in the ground electronic state.…”