Alternated Branching Ratios by Anomaly in Collision-Induced Dissociation of Proton-Bound Hoogsteen Base Pairs of 1-Methylcytosine with 1-Methylguanine and 9-Methylguanine.

A comparative study on the proton-bound complexes of 1-methylcytosine (1-mC) with 1-methylguanine (1-mG) and 9-methylguanine (9-mG), [1-mC:1-mG:H] and [1-mC:9-mG:H], respectively, was carried out using energy-resolved collision-induced dissociation (ER-CID) experiments in combination with quantum chemical calculations. In ER-CID experiments, the measured survival yields indicated an essentially identical stability for the two proton-bound complexes. In comparison with the lowest-energy structures and base-pairing energetics predicted at the B3LYP/6-311+G(2d,2p) theory level, both complexes produced in this study were suggested to be proton-bound Hoogsteen base pairs. Curiously, despite the similarity in structures, binding energetics, and potential energy surfaces predicted by the B3LYP theory, the fragment branching ratios exhibited an intriguing alternation between the two proton-bound Hoogsteen base pairs. The CID of [1-mC:1-mG:H] produced protonated cytosines, [1-mC:H], more abundantly than [1-mG:H], whereas that of [1-mC:9-mG:H] gave rise to a more pronounced production of protonated guanines, [9-mG:H]. However, using the proton affinities of moieties predicted by the high-accuracy methods, including CBS-QB3 and the Guassian-4 theory, the anomaly known for [Cytosine:Guanine:H] (J. Am. Soc. Mass Spectrom. 29, 2368-2379 (2018)) successfully accounted for the alternated branching ratios. Thereby, the anomaly, more specifically, the production of proton-transferred fragments of O-protonated cytosines in the CID of proton-bound Hoogsteen base pairs, is indeed real, which is disclosed as the alternated branching ratios in the CID spectra of [1-mC:1-mG:H] and [1-mC:9-mG:H] in this study. Graphical Abstract .