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1. Spin-orbit charge transfer from guanine and 9-methylguanine radical cations to nitric oxide radicals and the induced triplet-to-singlet intersystem crossing

   https://doi.org/10.1063/5.0160921  

   Benny, Jonathan; Liu, Jianbo (August 2023, The Journal of Chemical Physics)

   Nitric oxide (●NO) participates in many biological activities, including enhancing DNA radiosensitivity in ionizing radiation-based radiotherapy. To help understand the radiosensitization of ●NO, we report reaction dynamics between ●NO and the radical cations of guanine (a 9HG●+ conformer) and 9-methylguanine (9MG●+). On the basis of the formation of 9HG●+ and 9MG●+ in the gas phase and the collisions of the radical cations with ●NO in a guided-ion beam mass spectrometer, the charge transfer reactions of 9HG●+ and 9MG●+ with ●NO were examined. For both reactions, the kinetic energy-dependent product ion cross sections revealed a threshold energy that is 0.24 (or 0.37) eV above the 0 K product 9HG (or 9MG) + NO+ asymptote. To interrogate this abnormal threshold behavior, the reaction potential energy surface for [9MG + NO]+ was mapped out at closed-shell singlet, open-shell singlet, and triplet states using density functional and coupled cluster theories. The results showed that the charge transfer reaction requires the interaction of a triplet-state surface originating from a reactant-like precursor complex 3[9MG●+(↑)⋅(↑)●NO] with a closed-shell singlet-state surface evolving from a charge-transferred complex 1[9MG⋅NO+]. During the reaction, an electron is transferred from π∗(NO) to perpendicular π∗(9MG), which introduces a change in orbital angular momentum. The latter offsets the change in electron spin angular momentum and facilitates intersystem crossing. The reaction threshold in excess of the 0 K thermochemistry and the low charge-transfer efficiency are rationalized by the vibrational excitation in the product ion NO+ and the kinetic shift arising from a long-lived triplet intermediate. 

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2. Reaction mechanism and dynamics for C8-hydroxylation of 9-methylguanine radical cation by water molecules

   https://doi.org/10.1039/d1cp03884b  

   Zhou, Wenjing; Liu, Jianbo (November 2021, Physical Chemistry Chemical Physics)

   In contrast to their spontaneous deprotonation in aqueous solution, reactions of guanine and guanosine radical cations with water in the gas phase are exclusively initiated by hydration of the radical cations as reported in recent work (Y. Sun et al. , Phys. Chem. Chem. Phys. , 2018, 20 , 27510). As gas-phase hydration reactions closely mimic the actual scenario for guanine radical cations in double-stranded DNA, exploration of subsequent reactions within their water complexes can provide an insight into the resulting oxidative damage to nucleosides. Herein guided-ion beam mass spectrometry experiment and direct dynamics trajectory simulations were carried out to examine prototype complexes of the 9-methylguanine radical cation with one and two water ligands ( i.e. , 9MG˙ + ·(H 2 O) 1–2 ) in the gas phase, wherein the complexes were activated by collisional activation in the experiment and by thermal excitation at high temperatures in the simulations. Guided by mass spectroscopic measurements, trajectory results and reaction potential energy surface, three reaction pathways were identified. The first two reaction pathways start with H-atom abstraction from water by the O6 and N7 atoms in 9MG˙ + and are referred to as HA O6 and HA N7 , respectively. The primary products of HA O6 and HA N7 reactions, including [9MG + H O6 ] + /[9MG + H N7 ] + and ˙OH, react further to either form [8OH-9MG + H O6 ]˙ + and [8OH-9MG + H N7 ]˙ + via C8-hydroxylation or form radical cations of 6- enol -guanine (6- enol -G˙ + ) and 7H-guanine (7HG˙ + ) via S N 2-type methanol elimination. The third reaction pathway corresponds to the formation of 8OH-9MG + by H elimination from the complex, referred to as HE. Among these product channels, [8OH-9MG + H N7 ]˙ + has the most favorable formation probability, especially in the presence of additional water molecules. This product may serve as a preceding structure to the 8-oxo-7,8-dihydroguanine lesion in DNA and has implications for health effects of radiation exposure and radiation therapy. 

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3. 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

   https://doi.org/10.1039/d2cp00312k  

   Moe, May Myat; Benny, Jonathan; Liu, Jianbo (April 2022, Physical Chemistry Chemical Physics)

   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), i.e. , [9MG·9MG]˙ + , [9MOG·9MG]˙ + and [9MOG·9MOG]˙ + . Experimentally, collision-induced dissociation tandem mass spectrometry coupled with an electrospray ionization (ESI) source was used for the formation of base-pair radical cations, followed by detection of dissociation product ions and cross sections in the collisions with Xe gas under single ion–molecule collision conditions and as a function of the center-of-mass collision energy. Computationally, density functional theory and coupled cluster theory were used to calculate and identify probable base-pair structures and intra-base pair proton transfer and hydrogen transfer reactions, followed by kinetics modeling to explore the properties of dissociation transition states and kinetic factors. The significance of this work is twofold: it provides insight into base-pair opening kinetics in three biologically-important, non-canonical systems upon oxidative and ionization damage; and it links non-statistical dissociation to intra-base pair proton-transfer originating from the N1–H at the Watson–Crick edge of 8-oxoguanine, enhancing understanding towards the base-pair fragmentation assisted by proton transfer. 

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4. 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

   https://doi.org/10.1039/d0cp04243a  

   Sun, Yan; Moe, May Myat; Liu, Jianbo (November 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   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. Two types of conformers were distinguished by CID in which the conventional conformers produced [9MG + H] + product ions whereas the proton-transferred conformers produced [1MC + H] + . The conventional conformers have a higher population (99.8%) and lower dissociation energy than the proton-transferred counterparts. However, in contrast to what was expected from the statistical dissociation of the equilibrium base-pair conformational ensemble, the CID product ions of WC-[9MG·1MC + H] + were dominated by [1MC + H] + rather than [9MG + H] + . This finding, alongside the non-statistical CID reported for deprotonated guanine–cytosine (Lu et al. ; PCCP , 2016, 18 , 32222) and guanine–cytosine radical cation (Sun et al. ; PCCP , 2020, 22 , 14875), reinforces that non-statistical dissociation is a distinctive feature of singly-charged Watson–Crick guanine–cytosine base pairs. It implies that intra-base-pair PT facilitates the formation of proton-transferred conformers in these systems and the ensuing conformers have loose transition states for dissociation. The monohydrate of WC-[9MG·1MC + H] + preserves non-statistical CID kinetics and introduces collision-induced methanol elimination via the reaction of the water ligand with a methyl group. 

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

   https://doi.org/10.1002/cphc.202300511  

   Moe, May_Myat; Tsai, Midas; Liu, Jianbo (October 2023, ChemPhysChem)

   Abstract 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 (¹O₂) 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. We first detected base‐pair dissociation in collisions with the Xe gas, which provided insight into intra‐base pair proton transfer of 9MOG⋅⁺ ⋅ 1MC[9MOG − H_N1]⋅ ⋅ [1MC+H_N3′]⁺and subsequent non‐statistical base‐pair separation. We then measured the reaction of [9MOG ⋅ 1MC]⋅⁺with¹O₂, revealing the two most probable pathways, C5‐O₂addition and H_N7‐abstraction at 9MOG. Reactions were entangled with the two forms of 9MOG radicals and base‐pair structures as well as multi‐configurations between open‐shell radicals and¹O₂(that has a mixed singlet/triplet character). These were disentangled by utilizing approximately spin‐projected density functional theory, coupled‐cluster theory and multi‐referential electronic structure modeling. The work delineated base‐pair structural context effects and determined relative reactivity toward¹O₂as [9MOG − H]⋅>9MOG⋅⁺>[9MOG − H_N1]⋅ ⋅ [1MC+H_N3′]⁺≥9MOG⋅⁺ ⋅ 1MC. 

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