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Hydrogen-rich cation radicals (GATT + 2H) + ˙ and (AGTT + 2H) + ˙ represent oligonucleotide models of charged hydrogen atom adducts to DNA. These tetranucleotide cation radicals were generated in the gas phase by one-electron reduction of the respective (GATT + 2H) 2+ and (AGTT + 2H) 2+ dications in which the charging protons were placed on the guanine and adenine nucleobases. We used wavelength-dependent UV/Vis photodissociation in the valence-electron excitation region of 210–700 nm to produce action spectra of (GATT + 2H) + ˙ and (AGTT + 2H) + ˙ that showed radical-associated absorption bands in the near-UV (330 nm) and visible (400–440 nm) regions. Born–Oppenheimer molecular dynamics and density-functional theory calculations were used to obtain and rank by energy multiple (GATT + 2H) dication and cation-radical structures. Time-dependent density functional theory (TD-DFT) calculations of excited-state energies and electronic transitions in (GATT + 2H) + ˙ were augmented by vibronic spectra calculations at 310 K for selected low-energy cation radicals to provide a match with the action spectrum. The stable product of one-electron reduction was identified as having a 7,8-dihydroguanine cation radical moiety, formed by intramolecular hydrogen atom migration from adenine N-1–H. The hydrogen migration was calculated to have a transition state with a low activation energy, E a = 96.5 kJ mol −1 , and positive activation entropy, Δ S ‡ = 75 J mol −1 K −1 . This allowed for a fast isomerization of the primary reduction products on the ion-trap time scale of 150 ms that was substantially accelerated by highly exothermic electron transfer. 

ABSTRACT: We report the generation and spectroscopic study of hydrogen-rich DNA tetranucleotide cation radicals (GATC+2H)+• and (AGTC+2H)+•. The radicals were generated in the gas phase by one-electron reduction of the respective dications (GATC +2H)2+ and (AGTC+2H)2+ and characterized by collision-induced dissociation and photodissociation tandem mass spectrometry and UV−vis photodissociation action spectroscopy. Among several absorption bands observed for (GATC+2H)+•, the bands at 340 and 450 nm were assigned to radical chromophores. Timedependent density functional theory calculations including vibronic transitions in the visible region of the spectrum were used to provide theoretical absorption spectra of several low-energy tetranucleotide tautomers having cytosine-, adenine-, and thymine- based radical chromophores that did not match the experimental spectrum. Instead, the calculations indicated the formation of a new isomer with the 7,8-H-dihydroguanine cation radical moiety. The isomerization involved hydrogen migration from the cytosine N-3−H radical to the C-8 position in N-7-protonated guanine that was calculated to be 87 kJ mol−1 exothermic and had a low-energy transition state. Although the hydrogen migration was facilitated by the spatial proximity of the guanine and cytosine bases in the low-energy (GATC+2H)+• intermediate formed by electron transfer, the reaction was calculated to have a large negative activation entropy. Rice−Ramsperger−Kassel−Marcus (RRKM) and transition state theory kinetic analysis indicated that the isomerization occurred rapidly in hot cation radicals produced by electron transfer with the population-weighed rate constant of k = 8.9 × 103 s−1. The isomerization was calculated to be too slow to proceed on the experimental time scale in thermal cation radicals at 310 K. 

Non-covalent complexes of the short amyloid peptide motif Gly-Asn-Asn-Gln-Gln-Asn-Tyr (GNNQQNY) with peptide counterparts that were tagged with a diazirine ring at the N-termini (*GNNQQNY) were generated as singly charged ions in the gas phase. Specific laser photodissociation (UVPD) of the diazirine tag in the gas-phase complexes at 355 nm generated transient carbene intermediates that underwent covalent cross-linking with the target GNNQQNY peptide. The crosslinking yields ranged between 0.8 and 4.5%, depending on the combinations of peptide C-terminal amides and carboxylates. The covalent complexes were analyzed by collision-induced dissociation tandem mass spectrometry (CID-MS 3 ), providing distributions of cross-links at the target peptide amino acid residues. A general preference for cross-linking at the target peptide Gln-4-Gln-5-Asn-6-Tyr-7 segment was observed. Born–Oppenheimer molecular dynamics calculations were used to obtain 100 ps trajectories for nine lowest free-energy conformers identified by ωB97X-D/6-31+G(d,p) gradient geometry optimizations. The trajectories were analyzed for close contacts between the incipient carbene atom and the X–H bonds in the target peptide. The close-contact analysis pointed to the Gln-5 and Tyr-7 residues as the most likely sites of cross-linking, consistent with the experimental CID-MS 3 results. Non-covalent binding in the amide complexes was evaluated by DFT calculations of structures and energies. Although antiparallel arrangements of the GNNQQNY and *GNNQQNY peptides were favored in low-energy gas-phase and solvated complexes, the conformations and peptide–peptide interface surfaces were found to differ from the secondary structure of the dry interface in GNNQQNY motifs of amyloid aggregates.