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

Abstract

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 d 2 + ions, hydrogen atom migrations accompanying the formation of ( w 2 +H)+•, ( w 2 +2H)+, and ( d 2 +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.

Do d(GCGAAGC) Cations Retain the Hairpin Structure in the Gas Phase? A Cyclic Ion Mobility Mass Spectrometry and Density Functional Theory Computational Study

“…Electron transfer to oligonucleotide cations has been reported to cause dissociation at various levels, which were very low to practically none for hexanucleotides, weak for tetranucleotides, , and moderate to abundant for di- and trinucleotides. , In an effort to characterize the present heptanucleotide cations, we obtained ET-CID-MS 3 spectra of various charge states that were generated by nondissociative electron transfer, e.g., one-electron 3 + → 2 +• , 4 + → 3 +• , and two-electron 4 + → 2 + charge reducing reactions. The former two one-electron reductions generated open shell systems that were potentially susceptible to radical-induced dissociations, which are briefly described here.…”

Carbene Cross-Linking in Gas-Phase Peptide Ion Scaffolds

“…Born–Oppenheimer molecular dynamics (BOMD) calculations were run as 20 ps trajectories with 1 fs steps at 350–600 K using PM6-D3H4 calculations, as described previously . The BOMD calculations were run under the high-level Cuby4 platform .…”

“…Born−Oppenheimer molecular dynamics (BOMD) calculations were run as 20 ps trajectories with 1 fs steps at 350−600 K using PM6-D3H4 calculations, as described previously. 51 The BOMD calculations were run under the high-level Cuby4 platform. 52 The initial ion structures were constructed with different protonation sites that were at the peptide amide carbonyls for the nonbasic peptides (Ala, Leu, Gly, Pro) and the imidazole side chain for His.…”

Competitive Radical Migrations and Ribose Ring Cleavage in Adenosine and 2′-Deoxyadenosine Cation Radicals

“…Studies that have been aimed at the generation of cation radicals of nucleic acid components in the gas phase have addressed nucleobases, nucleosides, and oligonucleotides, as reviewed . In particular, hydrogen atom transfers in oligonucleotide cation radicals have been detected by tandem mass spectrometry that was coupled to UV–vis photodissociation action spectroscopy (UVPD) of gas-phase ions. − O’Hair and co-workers have used infrared multiphoton dissociation (IRMPD) spectroscopy to characterize the cytosine–guanosine Watson–Crick pair as a cation radical in the gas phase. These authors have also provided density-functional theory (DFT) calculations to rationalize the observed dissociations …”