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

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_ε-methyl-l-lysine-H⁺ (Me₁-lysine-H⁺), N_ε,N_ε-dimethyl-l-lysine-H⁺ (Me₂-lysine-H⁺), and N_ε,N_ε,N_ε-trimethyl-l-lysine-H⁺ (Me₃-lysine-H⁺). The major pathways observed in the experimental measurements were m/z 130 and 84, with the former dominant at low collision energies and the latter at intermediate to high collision energies. The m/z 130 peak corresponds to loss of N(CH₃)H_3-, while m/z 84 has the additional loss of H₂CO₂ likely in the form of H₂O + CO. Within the time frame of the direct dynamics simulations, m/z 130 and 101 were the most populous peaks, with the latter identified as an intermediate to m/z 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 m/z 84 peak population in simulations.