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. 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 ]⋅ ⋅ [1MC+H ] and subsequent non-statistical base-pair separation. We then measured the reaction of [9MOG ⋅ 1MC]⋅ with O , revealing the two most probable pathways, C5-O addition and H -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 and O (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 toward O as [9MOG - H]⋅>9MOG⋅ >[9MOG - H ]⋅ ⋅ [1MC+H ] ≥9MOG⋅  ⋅ 1MC.