Singlet Oxygen Oxidation of the Radical Cations of 8‐Oxo‐2′‐deoxyguanosine and Its 9‐Methyl Analogue: Dynamics, Potential Energy Surface, and Products Mediated by C5‐O₂‐Addition

Abstract

8‐Oxo‐2′‐deoxyguanosine (OG) is the most common DNA lesion. Notably, OG becomes more susceptible to oxidative damage than the undamaged nucleoside, forming mutagenic products in vivo. Herein the reactions of singlet O2 with the radical cations of 8‐oxo‐2′‐deoxyguanosine (OG.+) and 9‐methyl‐8‐oxoguanine (9MOG.+) were investigated using ion‐molecule scattering mass spectrometry, from which barrierless, exothermic O2‐addition products were detected for both reaction systems. Corroborated by static reaction potential energy surface constructed using multi‐reference CASPT2 theory and molecular dynamics simulated in the presence of the reactants′ kinetic and internal energies, the C5‐terminal O2‐addition was pinpointed as the most probable reaction pathway. By elucidating the reaction mechanism, kinetics and dynamics, and reaction products and energetics, this work constitutes the first report unraveling the synergetic damage of OG by ionizing radiation and singlet O2.

Collision-induced dissociation of homodimeric and heterodimeric radical cations of 9-methylguanine and 9-methyl-8-oxoguanine: correlation between intra-base pair proton transfer originating from the N1–H at a Watson–Crick edge and non-statistical dissociation

“…Conformation search was carried out using the density functional theory (DFT) ωB97XD with the 6-311++G(d,p) basis set. The ωB97XD functional 100 mitigates self-interaction errors and improves the orbital descriptions of base-pair radical cations as reported by Kumar et al 50 The same method was used in modeling 9MG˙ + , 86 9MOG˙ + , 87 and 9MG˙ + ·1MC 14 reactions in our previous work, with resulting PESs consistent with experimental measurements. Basis set superposition errors ( i.e.…”

“…Conformation search was carried out using the density functional theory (DFT) oB97XD with the 6-311++G(d,p) basis set. The oB97XD functional 100 mitigates self-interaction errors and improves the orbital descriptions of base-pair radical cations as reported by Kumar et al 50 The same method was used in modeling 9MG + , 86 9MOG + , 87 and 9MG + Á1MC 14 reactions in our previous work, with resulting PESs consistent with experimental measurements. Basis set superposition errors (i.e., a finite basis set stabilizes the complex more than the separate components and thus overestimates binding energy 101 ) for these base pairs were found to be less than 0.05 eV at the oB97XD/6-311++G(d,p) level and therefore have no influence on the order of stability of various conformers.…”

“…The experiment was carried out on our home-built guided-ion beam tandem mass spectrometer which was described elsewhere. 12,[85][86][87] Only critical instrumentation parameters were explicitly discussed. An electrospray ionization (ESI) source, maintained at a voltage of +2.2 kV with respect to the mass spectrometer inlet, was used to generate a variety of [Cu II (nucleobase) n ] 2+ complexes (wherein nucleobase = 9MG and/or 9MOG) from electrospray of a fresh-made mixture of 0.5 mM 9MG (Chemodex, 498%), 0.5 mM 9MOG (provided by B. Lippert, University of Dortmund, Germany 88 ) and 0.25 mM Cu(NO 3 ) 2 (Alfa Aesar, 499.999%) in methanol/water (v : v = 3 : 1).…”

Singlet O2 Oxidation of the Radical Cation versus the Dehydrogenated Neutral Radical of 9-Methylguanine in a Watson–Crick Base Pair. Consequences of Structural Context

“…Recently, electrospray ionization (ESI)-tandem mass spectrometry has emerged as a new approach for the formation and reactions of nucleobase radical cations in the gas phase. ,,,,− In this work, formation of [9MG·1MC] •+ and its reaction with 1 O 2 were carried out on a home-made ESI guided-ion beam scattering tandem mass spectrometer. Details of the apparatus have been reported in our previous work. , A methanol/water (v/v = 3:1) solution of 9MG, 1MC, and Cu­(NO 3 ) 2 in equimolar concentrations (0.25 mM) was freshly prepared and sprayed into the air through an ESI needle at a rate of 0.06 mL/h.…”

“…The calculation of the reaction PES for a radical with 1 O 2 is challenged by multi-configuration wavefunctions originating from the mixed open- and closed-shell character of 1 O 2 . The spin-restricted DFT cannot describe the static correlation arising from the two degenerate π* orbitals and overestimates the 1 O 2 excitation energy by 0.7 eV, whereas the unrestricted broken spin-symmetry DFT brings about spin contamination from 3 O 2 and underestimates the excitation by 0.5 eV. − This problem affects not only the 1 O 2 reactant but also the intermediates and TSs for 1 O 2 addition to the guanine radical. ,, In the latter case, the target doublet state 2 [[9MG·1MC] •+ (↑)··· 1 O 2 (↑↓)] not only suffers from spin contamination of a lower-energy lying quartet state 4 [[9MG·1MC] •+ (↑)··· 3 O 2 (↑↑)] but also mistakenly converges to a lower-energy but incorrect doublet state 2 [[9MG·1MC] •+ (↓)··· 3 O 2 (↑↑)].…”