Radical Cascade Dissociation Pathways to Unusual Nucleobase Cation Radicals

We report unusual dissociations of protonated RNA nucleosides tagged with radical initiator groups at ribose 5'-O and furnished with a 2',3'-O-isopropylidene protecting group. The ions undergo collision-induced radical cascade dissociations starting at the radical initiator that break down the dioxolane ring and trigger the formation of nucleobase cations and cation radicals. The adenine cation radical that was formed by radical cascade dissociations was identified by MS⁵ UV-vis photodissociation action spectroscopy to be a higher-energy N-3-H tautomer of the canonical ionized nucleobase. The guanine cation radical was formed by radical cascade dissociations as the N-7-H tautomer. In contrast to adenosine and guanosine, radical cascade dissociations of the tagged ribocytidine ion produced protonated cytosine, whereas tagged ribothymidine showed yet different dissociations resulting in predominant thymine loss. Reaction mechanisms were suggested for the cascade dissociations that were based on Born-Oppenheimer molecular dynamics and density functional theory calculations that were used to map the relevant parts of the potential energy surfaces for adenosine, guanosine, and cytidine radical ions. The reported radical cascade dissociations represent a new, nonredox approach to nucleobase and nucleoside cation radicals that has the potential of being expanded to the generation of various oligonucleotide cation radicals.