The chemistry of singlet O2 toward the guanine base of DNA is highly relevant to DNA lesion, mutation, cell death, and pathological conditions. This oxidative damage is initiated by the formation of a transient endoperoxide through the Diels-Alder cycloaddition of singlet O2 to the guanine imidazole ring. However, no endoperoxide formation was directly detected in native guanine or guanosine, even at -100 °C. Herein, gas-phase ion-molecule scattering mass spectrometry was utilized to capture unstable endoperoxides in the collisions of hydrated guanine ions (protonated or deprotonated) with singlet O2 at ambient temperature. Corroborated by results from potential energy surface exploration, kinetic modeling, and dynamics simulations, various aspects of endoperoxide formation and transformation (including its dependence on guanine ionization and hydration states, as well as on collision energy) were determined. This work has pieced together reaction mechanisms, kinetics, and dynamics data concerning the early stage of singlet O2 induced guanine oxidation, which is missing from conventional condensed-phase studies.
Mutagenicity of singlet O2 is due to its oxidatively generated damage to the guanine nucleobases of DNA. Oxidation of neutral guanosine has been assumed to be initiated by the formation of a transient 4,8-endoperoxide via a Diels-Alder cycloaddition of singlet O2. Protonation and deprotonation of guanosine represent another factor related to DNA damage and repair. Herein, 9-methylguanine was utilized as a model substrate to mimic the correlation between singlet O2 oxidation of the nucleoside and its ionization states, both in the absence and in the presence of water ligands. We used guided-ion-beam scattering tandem mass spectrometry to detect and quantify transient intermediates at room temperature. To provide a reliable description of reaction potential surfaces, different levels of theory including restricted and unrestricted density functional theory, CCSD(T), MP2, and multi-reference CASSCF and CASMP2 were applied. By means of molecular potential, kinetic and direct dynamics simulations, two reaction pathways were identified and neither follows the mechanism for neutral guanosine. Singlet O2 oxidation of protonated 9-methylguanine begins by a concerted cycloaddition; but it is mediated by a 5,8-endoperoxide. By contrast, a concerted cycloaddition does not occur for deprotonated 9-methylguanine. The latter involves a stepwise addition starting with the formation of an 8-peroxide, which subsequently evolves to a 4,8-endoperoxide. This dichotomy implies that acidic and basic media may lead to different chemistries for guanosine oxidation in aqueous solutions, starting from initial stage. The comparison with oxidation of protonated/deprotonated guanine illustrates the different mechanisms and products and particularly the suppressed oxidizability of 9-methylguanine vs. free guanine.
Polycyclic aromatic hydrocarbons (PAHs) have been invoked in fundamental molecular mass growth processes in our galaxy. We provide compelling evidence of the formation of the very first ringed aromatic and building block of PAHs—benzene—via the self-recombination of two resonantly stabilized propargyl (C3H3) radicals in dilute environments using isomer-selective synchrotron-based mass spectrometry coupled to theoretical calculations. Along with benzene, three other structural isomers (1,5-hexadiyne, fulvene, and 2-ethynyl-1,3-butadiene) and o-benzyne are detected, and their branching ratios are quantified experimentally and verified with the aid of computational fluid dynamics and kinetic simulations. These results uncover molecular growth pathways not only in interstellar, circumstellar, and solar systems environments but also in combustion systems, which help us gain a better understanding of the hydrocarbon chemistry of our universe.
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