Gas-phase Reactivity of meta-Benzyne Analogs Toward Small Oligonucleotides of Differing Lengths

Abstract

Abstract. The gas-phase reactivity of two aromatic carbon-centered σ,σ-biradicals (meta-benzyne analogs) and a related monoradical towards small oligonucleotides of differing lengths was investigated in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with laser-induced acoustic desorption (LIAD). The mono-and biradicals were positively charged to allow for manipulation in the mass spectrometer. The oligonucleotides were evaporated into the gas phase as intact neutral molecules by using LIAD. One of the biradicals was found to be unreactive. The reactive biradical reacts with dinucleoside phosphates and trinucleoside diphosphates mainly by addition to a nucleobase moiety followed by cleavage of the glycosidic bond, leading to a nucleobase radical (e.g., base-H) abstraction. In some instances, after the initial cleavage, the unquenched radical site of the biradical abstracts a hydrogen atom from the neutral fragment, which results in a net nucleobase abstraction. In sharp contrast, the related monoradical mainly undergoes facile hydrogen atom abstraction from the sugar moiety. As the size of the oligonucleotides increases, the rate of hydrogen atom abstraction from the sugar moiety by the monoradical was found to increase due to the presence of more hydrogen atom donor sites, and it is the only reaction observed for tetranucleoside triphosphates. Hence, the monoradical only attacks sugar moieties in these substrates. The biradical also shows significant attack at the sugar moiety for tetranucleoside triphosphates. This drastic change in reactivity indicates that the size of the oligonucleotides plays a key role in the outcome of these reactions. This finding is attributed to more compact conformations in the gas phase for the tetranucleoside triphosphates than for the smaller oligonucleotides, which result from stronger stabilizing interactions between the nucleobases.

Spin‐Spin Coupling Controls the Gas‐Phase Reactivity of Aromatic σ‐Type Triradicals

“…Aromatic carbon-centered σ-type mono-and biradicals, including the phenyl radical and the three isomeric benzynes, have been researched for more than a century due to their role as important reaction intermediates [1,2] and their potential applications in a variety of fields, such as organic synthesis, [3,4] polymer chemistry, [5] materials science, [6] and anticancer therapeutics. [7][8][9][10][11] Due to the difficulty of cleanly generating many mono-and biradicals in solution (with the exception of ortho-benzyne analogs), [1,12] the ion-molecule reactions of related charged mono-and biradicals have been studied in the gas phase by using mass spectrometry. [13][14][15][16][17][18][19][20][21][22][23] Based on the literature, radical reactions should be fairly insensitive to solvent effects, [24] which facilitates the comparison of the gas-phase and solution reactions.…”