Reactivity of aromatic σ,σ-biradicals toward riboses

Abstract

The gas-phase reactions of sugars with aromatic, carbon-centered ,-biradicals with varying polarities [as reflected by their calculated electron affinities (EA)] and extent of spin-spin coupling [as reflected by their calculated singlet-triplet (S-T) gaps] have been studied. The biradicals are positively charged, which allows them to be manipulated and their reactions to be studied in a Fourier-transform ion cyclotron resonance mass spectrometer. Hydrogen atom abstraction from sugars was found to be the dominant reaction for the biradicals with large EA values, while the biradicals with large S-T gaps tend to form addition/elimination products instead. Hence, not all ,-biradicals may be able to damage DNA by hydrogen atom abstraction. The overall reaction efficiencies of the biradicals towards a given substrate were found to be directly related to the magnitude of their EA values, and inversely related to their S-T gaps. The EA of a biradical appears to be a very important rate-controlling factor, and it may even counterbalance the reduced radical reactivity characteristic of singlet biradicals that have large S-T gaps. . These intermediates are believed to irreversibly damage double-stranded DNA via hydrogen atom abstraction from a sugar moiety in each strand [2]. Therefore, a better understanding of the factors controlling the reactivity of these biradicals toward sugars is important.Solution [3] and gas-phase [4] studies on the reactivity of neutral and charged phenyl radicals have confirmed that these monoradicals can abstract hydrogen atoms from sugars as well as from the sugar moiety in nucleosides and dinucleoside phosphates. Polar effects (i.e., polarization of the transition state) play a major role in controlling these reactions [5][6][7]. However, no such studies have been reported for the analogous biradicals.The magnitude of the singlet-triplet (S-T) gap has been proposed earlier [8] as the major reaction rate controlling factor for aromatic ,-biradicals with singlet ground states. As the magnitude of the S-T gap increases, the reaction efficiency for hydrogen atom abstraction from simple substrates has been observed to decrease, presumably because of the energetically high cost of uncoupling the biradical's electrons in the transition state [8,9]. Biradicals with large S-T gaps appear to avoid this penalty by undergoing nucleophilic or electrophilic (nonradical) addition reactions [10]. Recent gas-phase studies have shown that in addition to S-T gap effects [9], reactions of biradicals with simple organic substrates are also sensitive to polar effects (which is reflected by the biradical's calculated vertical electron affinity, EA) [11]. Here, we report an examination of the reactivity of several ,-biradicals (Scheme 1) toward various sugars, and show that these reactions are also affected by the S-T gap and the EA of the biradical.

Reactions of an aromatic σ,σ-biradical with amino acids and dipeptides in the gas phase

“…The particular biradical selected for this study can be generated in high abundance by using procedures reported [39,40] previously, which makes it ideal for the very challenging experiments described here. In order to avoid the possibility of proton transfer reactions ( i.e , the proton transfer pathway dominates the reaction of the protonated monoradical 3-dehydropyridinium with valine, proline, cysteine and methionine [31]), the biradical was N -methylated in this study.…”

“…The foil was mounted onto a manual insertion LIAD probe equipped with an optical fiber [35,39,40,53], which was inserted into the mass spectrometer. The amino acid and peptide molecules were evaporated into the cell by using 30–300 laser shots (Continuum Minilite Nd:YAG laser, light of 532-nm wavelength, 3-ns pulse width, 10-Hz repetition rate) applied in a circular pattern on the backside of a Ti foil (the side opposite to where the sample was deposited).…”

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

“…This is followed by homolytic cleavage of -anion (Scheme 6) [59]. Further, a previous gas-phase study on a charged aromatic σ,σ-biradical, the N-methyl-4,6-didehydroisoquinolinium cation, suggests that the attack of the biradical on riboses is initiated by hydrogen atom abstraction by the radical site at C4 [9]. Hence, an initial hydrogen atom abstraction from a sugar moiety of a tetranucleoside triphosphate by the most electrophilic radical site in N-methyl-6,8-didehydroquinolinium cation (C6; see above), followed by an analogous fragmentation as proposed for the formationofthe[C 5 H 5 O 2 ] -anion(Scheme6),mayexplainthefirststepsof C 5 H 6 O 2 abstraction by the N-methyl-6,8-didehydroquinolinium cation.…”

“…The distonic ion approach has been utilized to investigate the reactivities of many biradicals toward small organic molecules as well as DNA components in mass spectrometers [7][8][9]. Recent studies have shown that charged radicals behave similarly in the gas phase and in solution [10].…”

“…Therefore, a larger S-T splitting results in higher transition state energies for reactions of the biradical. Indeed, a previous study has shown that singlet ground state σ,σ-biradicals with a large S-T splitting are either unreactive or attack riboses via non-radical pathways [9].…”