Effects of Intra-Base Pair Proton Transfer on Dissociation and Singlet Oxygenation of 9-Methyl-8-Oxoguanine-1-Methyl-Cytosine Base-Pair Radical Cations.

8-Oxoguanosine is the most common oxidatively generated base damage and pairs with complementary cytidine within duplex DNA. The 8-oxoguanosine-cytidine lesion, if not recognized and removed, not only leads to G-to-T transversion mutations but renders the base pair being more vulnerable to the ionizing radiation and singlet oxygen ( O ) damage. Herein, reaction dynamics of a prototype Watson-Crick base pair [9MOG ⋅ 1MC]⋅ , consisting of 9-methyl-8-oxoguanine radical cation (9MOG⋅ ) and 1-methylcystosine (1MC), was examined using mass spectrometry coupled with electrospray ionization.

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

In DNA, guanine is the most susceptible to oxidative damage by exogenously and endogenously produced electronically excited singlet oxygen (O). The reaction mechanism and the product outcome strongly depend on the nucleobase ionization state and structural context. Previously, exposure of a monomeric 9-methylguanine radical cation (9MG, a model guanosine compound) to O was found to result in the formation of an 8-peroxide as the initial product.

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.

It has been shown previously in protonated, deprotonated and ionized guanine-cytosine base pairs that intra-base pair proton transfer from the N1-H at the Watson-Crick edge of guanine to the complementary nucleobase prompts non-statistical dissociation of the base-pair system, and the dissociation of a proton-transferred base-pair structure is kinetically more favored than that of the starting, conventional base-pair structure. However, the fundamental chemistry underlying this anomalous and intriguing kinetics has not been completely revealed, which warrants the examination of more base-pair systems in different structural contexts in order to derive a generalized base-pair structure-kinetics correlation. The purpose of the present work is to expand the investigation to the non-canonical homodimeric and heterodimeric radical cations of 9-methylguanine (9MG) and 9-methyl-8-oxoguanine (9MOG), , [9MG·9MG]˙, [9MOG·9MG]˙ and [9MOG·9MOG]˙.

Singlet O Reactions with Radical Cations of 8-Bromoguanine and 8-Bromoguanosine: Guided-Ion Beam Mass Spectrometric Measurements and Theoretical Treatments.

8-Bromoguanosine is generated in vivo as a biomarker for early inflammation. Its formation and secondary reactions lead to a variety of biological sequelae at inflammation sites, most of which are mutagenic and linked to cancer. Herein, we report the formation of radical cations of 8-bromoguanine (8BrG) and 8-bromoguanosine (8BrGuo) and their reactions toward the lowest excited singlet molecular oxygen (O)─a common reactive oxygen species generated in biological systems.

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-O -Addition.

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 O 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 O -addition products were detected for both reaction systems.

Experimental and theoretical assessment of protonated Hoogsteen 9-methylguanine-1-methylcytosine base-pair dissociation: kinetics within a statistical reaction framework.

We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine-1-methylcytosine base pair (HG-[9MG·1MC + H]+), which aims to address the mystery of the literature reported "anomaly" in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H]+ (reported recently by Sun et al.; Phys. Chem.

Dynamics and Multiconfiguration Potential Energy Surface for the Singlet O Reactions with Radical Cations of Guanine, 9-Methylguanine, 2'-Deoxyguanosine, and Guanosine.

Reactions of electronically excited singlet oxygen (O) with the radical cations of guanine (9HG), 9-methylguanine (9MG), 2'-deoxyguanosine (dGuo), and guanosine (Guo) were studied in the gas phase by a combination of guided-ion-beam mass spectrometric measurement of product ions and cross sections as a function of collision energy () and electronic structure calculations of the reaction potential energy surface (PES) at various levels of theory. No product could be captured in the O reaction with bare 9HG or 9MG, because energized products decayed rapidly to reactants before being detected. To overcome this unfavorable kinetics, monohydrated 9HG·HO and 9MG·HO were used as reactant ions, of which the peroxide product ions were stabilized by energy relaxation elimination of the water ligand.

Is non-statistical dissociation a general feature of guanine-cytosine base-pair ions? Collision-induced dissociation of a protonated 9-methylguanine-1-methylcytosine Watson-Crick base pair, and comparison with its deprotonated and radical cation analogues.

A guided-ion beam tandem mass spectrometric study was performed on collision-induced dissociation (CID) of a protonated 9-methylguanine-1-methylcytosine Watson-Crick base pair (designated as WC-[9MG·1MC + H]), from which dissociation pathways and dissociation energies were determined. Electronic structure calculations at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory were used to identify product structures and delineate reaction mechanisms. Intra-base-pair proton transfer (PT) of WC-[9MG·1MC + H] results in conventional base-pair conformations that consist of hydrogen-bonded [9MG + H] and 1MC and proton-transferred conformations that are formed by PT from the N1 of [9MG + H] to the N3' of 1MC.

Mass spectrometry and computational study of collision-induced dissociation of 9-methylguanine-1-methylcytosine base-pair radical cation: intra-base-pair proton transfer and hydrogen transfer, non-statistical dissociation, and reaction with a water ligand.

A combined experimental and theoretical study is presented on the collision-induced dissociation (CID) of 9-methylguanine-1-methylcytosine base-pair radical cation (abbreviated as [9MG·1MC]˙+) and its monohydrate ([9MG·1MC]˙+·H2O) with Xe and Ar gases. Product ion mass spectra were measured as a function of collision energy using guided-ion beam tandem mass spectrometry, from which cross sections and threshold energies for various dissociation pathways were determined. Electronic structure calculations were performed at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory to identify product structures and map out reaction potential energy surfaces.

Reactions of water with radical cations of guanine, 9-methylguanine, 2'-deoxyguanosine and guanosine: keto-enol isomerization, C8-hydroxylation, and effects of N9-substitution.

The reactions of D2O with radical cations of guanine (9HG˙+), 9-methylguanine (9MG˙+), 2'-deoxyguanosine (dGuo˙+) and guanosine (Guo˙+) were studied in the gas phase, including measurements of reaction cross sections over a center-of-mass collision energy (Ecol) range from 0.1 to 2.0 eV and computation of reaction pathways at DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-31+G(d,p).