Nucleoside Cation Radicals: Generation, Radical-Induced Hydrogen Atom Migrations, and Ribose Ring Cleavage in the Gas Phase

Nucleoside ions that were furnished on ribose with a 2′-O-acetyl radical group were generated in the gas phase by multistep collision-induced dissociation of precursor ions tagged with radical initiator groups, and their chemistry was investigated in the gas phase. 2′-O-Acetyladenosine cation radicals were found to undergo hydrogen transfer to the acetoxyl radical from the ribose ring positions that were elucidated using specific deuterium labeling of 1′-H, 2′-H, and 4′-H and in the N–H and O–H exchangeable positions, favoring 4′-H transfer. Ion structures and transition-state energies were calculated by a combination of Born–Oppenheimer molecular dynamics and density functional theory and used to obtain unimolecular rate constants for competitive hydrogen transfer and loss of the acetoxyl radical. Migrations to the acetoxyl radical of ribose hydrogens 1′-H, 2′-H, 3′-H, and 4′-H were all exothermic, but product formation was kinetically controlled. Both Rice–Ramsperger–Kassel–Marcus (RRKM) and transition-state theory (TST) calculations indicated preferential migration of 4′-H in a qualitative agreement with the deuterium labeling results. The hydrogen migrations displayed substantial isotope effects that along with quantum tunneling affected the relative rate constants and reaction branching ratios. UV–vis action spectroscopy indicated that the cation radicals from 2′-O-acetyladenosine consisted of a mixture of isomers. Radical-driven dissociations were also observed for protonated guanosine, cytosine, and thymidine conjugates. However, for those nucleoside ions and cation radicals, the dissociations were dominated by the loss of the nucleobase or formation of protonated nucleobase ions.