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 _ε -methyl-l-lysine-H ⁺ (Me ₁ -lysine-H ⁺ ), N _ε , N _ε -dimethyl-l-lysine-H ⁺ (Me ₂ -lysine-H ⁺ ), and N _ε , N _ε , N _ε -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(CH ₃ ) _n H _{3- n} , while m / z 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, 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.