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 Llysine-H+ and its side-chain methylated analogues, N-epsilon-methyl-L-lysine-H+ (Me-1-lysine-H+), N-epsilon,N-epsilon-dimethyl-L-lysine-H+ (Me-2-lysine-H+), and N-epsilon,N-epsilon,N-epsilon-trimethyl-L-lysine-H+ (Me-3- 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)(n) H3-n, 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.