Experimental and Theoretical Investigation of the Decomposition of Lithiated Hydroxyl Side-Chain Amino Acids

Abstract

Lithium cation complexes with serine (Ser) and threonine (Thr) are collisionally activated with xenon in a guided ion beam tandem mass spectrometer and are observed to exhibit a variety of decomposition pathways in addition to a loss of the intact ligand. Prominent pathways include a loss of H2O, CO2, and aldehydes (XCHO where X=H for Ser and CH3 for Thr). Quantum chemical calculations at the B3LYP/6-311+G(d,p) level are used to explore the reaction mechanisms for these processes in detail. Complete potential energy surfaces for all three processes are elucidated, including all intermediates and transition states. Theoretical molecular parameters for the rate-limiting transition states are then used to analyze the threshold energies in the experimental data, providing experimental measurements of the energies of these transition states. These experimental energies are compared with single-point energies calculated at three different levels, B3LYP, B3P86, and MP2(full), using the 6-311+G(2d,2p) basis set with geometries and zero-point energies calculated at the B3LYP/6-311+G(d,p) level. Good agreement between experiment and theory (especially MP2(full)) suggests that the reaction mechanisms have been reasonably elucidated.

Re-print of “Theoretical Investigation and Reinterpretation of the Decomposition of Lithiated Proline and N-Methyl Proline”

“…As noted above, the competitive shift observed in the Li + (Pro) system is about 0.14 eV, consistent with previous results for similarly sized systems [43,44]. In the case of Li + (NMP), analysis of the Li + cross section with and without including competition with CO loss gives the same threshold energy of ∼3.4 eV, but utilizes very different n values.…”

“…This difference is in agreement with the previous study [5] and with theory, which predicts an increase of 8-15 kJ/mol. This increase in the Li + binding energy upon methylation also agrees with increases measured for similar methylated systems studied previously [5,44,[51][52][53].…”

“…The threshold for Li + formation has also decreased by 0.13 eV as a result of accounting for the competition with the low energy channels. This competitive shift is comparable to those observed for fragmentations of Li + (Met), Li + (Ser), and Li + (Thr) [43,44].…”

“…S2. As discussed in the Supplementary data, these processes appear to result from a water adduct of a contaminant or rearranged Li + (AA) formed in the source, which has been observed for other lithiated amino acids [44,45]. Because these products do not result from decomposition of the intact Li + (AA) complexes, they should not be included in the following analysis.…”

Dissociations of Complexes Between Monovalent Metal Ions and Aromatic Amino Acid or Histidine

“…Alternatively, CO 2 elimination could occur first, leading to complex III, where the metal is coordinated to the side chain and contains an M─C bond, reminiscent of the mechanism proposed by Ye and Armentrout for the loss of CO 2 from lithium complexes with serine and threonine [48]. , it was previously reported that the 61 Da loss could also involve H 2 O and HNCO [17].…”