Gas phase click chemistry via ion/ion reactions

Abstract

The 1,3-dipolar cycloaddition between azides and alkynes, i.e., ‘click’ chemistry, has been demonstrated in the gas phase via ion/ion reactions. Doubly protonated azide-modified peptide cations were reacted with singly deprotonated dibenzoazacyclooctyne DIBAC reagent anions to form a long-lived complex monocation. Similarly, ion/ion complex monoanions were generated in the negative mode via reactions between singly protonated azide-containing cations and doubly deprotonated DIBAC reagent anions. Activation of ion/ion complexes in either polarity resulted in the formation of a triazole, a covalent linkage that can be further probed via MSn. The click chemistry coupled species synthesized in solution and subsequently transferred into the gas phase yielded the same products as those synthesized in gas phase when activated in the mass spectrometer. Analogous click chemistry products were synthesized in the solution phase and activated via tandem mass spectrometry as a control for the dissociation of the novel gas-phase reaction products. Density functional theory (DFT) calculations were performed to provide estimates for key processes (e.g., reaction barriers and energies) that can occur in the overall reaction. The work herein demonstrates that it is possible to conjugate azide and alkyne functional groups in the gas-phase, and represents another example of the growing number of selective covalent reactions that can take place via gas-phase ion/ion reactions.