The DNA Radical Code. Resolution of Identity in Dissociations of Trinucleotide Codon Cation Radicals in the Gas Phase

Sixty DNA trinucleotide cation radicals covering a large part of the genetic code alphabet were generated by electron transfer in the gas phase, and their chemistry was studied by collision-induced dissociation tandem mass spectrometry and theoretical calculations. The major dissociations involved loss of nucleobase molecules and radicals, backbone cleavage, and cross-ring fragmentations that depended on the nature and position of the nucleobases. Mass identity in dissociations of symmetrical trinucleotide cation radicals of the (XXX+2H)^+• and (XYX+2H)^+• type was resolved by specific ¹⁵N labeling. The specific features of trinucleotide cation radical dissociations involved the dominant formation of ions, hydrogen atom migrations accompanying the formation of (+H)^+•, (+2H)⁺, and (+2H)⁺ sequence ions, and cross-ring cleavages in the 3'- and 5'-deoxyribose moieties that depended on the nucleobase type and its position in the ion. Born-Oppenheimer molecular dynamics (BOMD) and density functional theory calculations were used to obtain structures and energies of several cation-radical protomers and conformers for (AAA+2H)^+•, (CCC+2H)^+•, (GGG+2H)^+•, (ACA+2H)^+•, and (CAA+2H)^+• that were representative of the different types of backbone dissociations. The ion electronic structure, protonation and radical sites, and hydrogen bonding were used to propose reaction mechanisms for the dissociations.