pH-Dependent Singlet O₂ Oxidation Kinetics of Guanine and 9-Methylguanine: An Online Mass Spectrometry and Spectroscopy Study Combined with Theoretical Exploration

Abstract

We report a kinetic and mechanistic study on the title reactions, in which O was generated by the reaction of HO with Cl and bubbled into an aqueous solution of guanine and 9-methylguanine (9MG) at different pH values. Oxidation kinetics and product branching ratios were measured using online electrospray ionization mass spectrometry coupled with absorption and emission spectrophotometry, and product structures were determined by collision-induced dissociation (CID) tandem mass spectrometry. Experiments revealed strong pH dependence of the reactions. The oxidation of guanine is noticeable only in basic solution, while the oxidation of 9MG is weak in acidic solution, increases in neutral solution, and becomes intensive in basic solution. 5-Guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) were detected as the major oxidation products of guanine and 9MG, and Sp became dominant in basic solution. A reaction intermediate was captured in mass spectra, and assigned to gem-diol on the basis of CID measurements. This intermediate served as the precursor for the formation of Gh. After taking into account solution compositions at each pH, first-order oxidation rate constants were extracted for individual species: that is, 3.2-3.6 × 10 M s for deprotonated guanine, and 1.2 × 10 and 4.6-4.9 × 10 M s for neutral and deprotonated 9MG, respectively. Guided by approximately spin-projected density-functional-theory-calculated reaction potential energy surfaces, the kinetics for the initial O addition to guanine and 9MG was evaluated using transition state theory (TST). The comparison between TST modeling and experiment confirms that O addition is rate-limiting for oxidation, which forms endoperoxide and peroxide intermediates as determined in previous measurements of the same systems in the gas phase.

Singlet O2 Oxidation of a Deprotonated Guanine‐Cytosine Base Pair and Its Entangling with Intra‐Base‐Pair Proton Transfer

“…The so‐calculated 1 O 2 excitation energy is 1.02 eV, which agrees wells with the experimental value of 0.98 eV . This spin‐projection method has been used for the PESs of 1 O 2 addition to guanine and 9MG,, and calculated reaction barriers are consistent with experimental results …”

“…We have recently reported the 1 O 2 oxidation dynamics and kinetics of guanine and 9‐methylguanine (9MG, a guanosine prototype compound) in the gas phase and in aqueous solution . Transient endoperoxides and peroxides of guanine and 9MG were captured using guided‐ion‐beam scattering techniques, oxidation rate constants and product branching ratios were determined using online mass spectrometry and spectroscopy, and reaction mechanisms were delineated with the aid of dynamics simulations and reaction potential energy surfaces (PESs).…”

“…The oxidation of [G ⋅ C−H] − would thus entangle with guanine tautomerization and intra‐base‐pair PT. The consequences are that the actual ionization state of the guanine moiety hinges on intra‐base‐pair PT; and the change of the ionization state in turn alters the oxidation of guanine …”

Superhydrophobic Photosensitizers: Airborne 1O2 Killing of an in Vitro Oral Biofilm at the Plastron Interface

“…Other airborne 1 O 2 reactions have been useful for reactions at solid surfaces, including the single molecule detection of 1 O 2 at a TiO 2 surface, 17–19 with 1 O 2 in thin films 20 and in conjugated polymers, 21,22 and in 1 O 2 bubbling systems in mass spectrometry. 23,24…”

Computational Study of the pH-Dependent Competition between Carbonate and Thymine Addition to the Guanine Radical

“…11,13−23 Oxidation of guanine radical leads to 8oxoG, Sp, Gh, 2Ih, and related products. 8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]27,28,[31][32][33][34][35][36]45 In competition with these oxidation pathways, guanine radical can form cross-links with amino acids and nucleobases. 11,13,[19][20][21][22]26,29,46 The formation of guanine-thymine cross-links has been studied largely using carbonate and sulfate radicals to selectively oxidize guanine.…”