Exploring the Effects of Methylation on the CID of Protonated Lysine: A Combined Experimental and Computational Approach

We report the results of experiments, simulations, and DFT calculations that focus on describing the reaction dynamics observed within the collision-induced dissociation of L-lysine-H$^+$ and its side-chain methylated analogues, $N_\epsilon$-Methyl-L-lysine-H$^+$ (\methylLysH{1}), $N_\epsilon$,$N_\epsilon$-Dimethyl-L-lysine-H$^+$ (\methylLysH{2}), and $N_\epsilon$,$N_\epsilon$,$N_\epsilon$-Trimethyl-L-lysine-H$^+$ (\methylLysH{3}). The major pathways observed in the experimental measurements were \mz 130 and 84, with the former dominant at low collision energies and the latter at intermediate to high collision energies. The \mz 130 peak corresponds to loss of N(CH$_3$)$_n$H$_{3-n}$ while \mz 84 has the additional loss of H$_2$CO$_2$ likely in the form of H$_2$O+CO. Within the time frame of the direct dynamics simulations, \mz 130 and 101 were the most populous peaks, with the latter identified as an intermediate to \mz 84. The simulations allowed for the determination of several reaction pathways that result in these products. A graph theory analysis enabled the elucidation of the significant structures that compose each peak. Methylation results in the preferential loss of the side-chain amide group and a reduction of cyclic structures within the \mz 84 peak population in simulations.