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), 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.