Gas-Phase Dipeptide Fragmentation Catalyzed by Alkali Metal Ions (Li ⁺ and Na ⁺ ): Revealing an Alternative Pathway for Gas-Phase Peptide Formation

A comprehensive computational study was performed to examine the gas-phase fragmentation pathways of six model dipeptides (Gly-Gly, Ala-Gly, Ala-Gln, Ala-Phe, Phe-Ala, and Tyr-Ala) coordinated with Li+ or Na+ in both cis and trans peptide bond configurations. Although these alkali metal cations are abundant in astrophysical environments, their specific roles in peptide fragmentation under nonradiative conditions have remained largely uncharacterized. The fragmentation was found to proceed through a two-step mechanism involving ring formation and multiple bond cleavages yielding three fragments including CO, an imine, and a metal-bound amino acid. Calculated activation energies (at 0 K) and rate constants (at 298 K for kinetic comparisons) revealed that both the peptide bond geometry and the identity of the alkali metal ion strongly influenced the reaction pathway. The extremely small obtained rate constants further indicate that gas-phase dipeptide fragmentation is not thermally accessible and require internal energy, supplied by alkali ion–dipeptide collisions. Intramolecular hydrogen bonding, particularly in Ala-Gln, was shown to significantly alter the fragmentation in the presence of Li+ and Na+. In addition to bond cleavage, recombination complexes formed from the three fragments (CO, an imine, and an alkali ion-bound amino acid), via the electrostatic interactions and directional hydrogen bonding, were identified. These complexes could be considered as plausible intermediates for gas phase peptide formation, highlighting the role of alkali cations as electrostatic templates that stabilize reactive intermediates and orient three fragments. For the first time, intrinsic activation energies and rate constants are reported for alkali metal–catalyzed dipeptide fragmentation, offering new insight into ion-specific mechanisms of peptide degradation and reassembly in the gas phase.