Gas-Phase Internal Proton-Transfer of Protonated para-Aminobenzoic Acid Catalyzed by One Methanol Molecule

Boris Ucur; Oisin J Shiels; Stephen J Blanksby; Adam J Trevitt

doi:10.1021/jasms.3c00118

Gas-Phase Internal Proton-Transfer of Protonated para-Aminobenzoic Acid Catalyzed by One Methanol Molecule

J Am Soc Mass Spectrom. 2023 Jul 5;34(7):1428-1435. doi: 10.1021/jasms.3c00118. Epub 2023 Jun 8.

Authors

Boris Ucur¹, Oisin J Shiels¹, Stephen J Blanksby², Adam J Trevitt¹

Affiliations

¹ Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales 2522, Australia.
² School of Chemistry and Physics and the Central Analytical Research Facility, Queensland University of Technology, Brisbane 4001, Australia.

PMID: 37288560
DOI: 10.1021/jasms.3c00118

Abstract

Electrospray ionization (ESI) is used to deliver analytes for mass analysis across a huge range of mass spectrometry applications. Despite its ubiquitous application and many mechanistic investigations, it remains that a fundamental understanding of ESI processes is not complete. In particular, all the factors that influence the populations of protonation isomers are elusive such that it remains a challenge to optimize experimental conditions to favor one isomer over another. The molecule para-aminobenzoic acid has emerged as an archetype for the study of protonation isomers, with both amino and carboxylic acid protonation site isomers (protomers) typically formed upon ESI, with the isomer ratio shown to be sensitive to several physical and chemical parameters. Here we report an ion-trap mass spectrometry study of the time-resolved methanol-catalyzed proton transfer between the amine and carboxylic acid moieties of para-aminobenzoic acid. The experimental and computational results presented are consistent with a bimolecular mechanism where isomerization is mediated by a single methanol rather than a multimolecular Grotthuss proton transfer process. Pseudo-first-order rate constants for protomer specific product ions are reported and confirm the depletion of the amino protomer is correlated to the growth of the carboxylic acid protomer. Under the controlled conditions of a low-pressure ion-trap mass spectrometer (2.5 mTorr, 300 K), the number of methanol molecules required to isomerize para-aminobenzoic acid is determined to be one, and the second-order rate constant for methanol-catalyzed isomerization is (1.9 ± 0.1) × 10^-11 cm³ molecule^-1 s^-1. The para-aminobenzoic acid vehicle mechanism is explored computationally at the DSD-PBEP86-D3BJ/aug-cc-pVDZ level of theory and reveals that the transition state for proton transfer is submerged (-10 kJ mol^-1) relative to the separated reactant energies. The findings from this paper show that single-solvent catalyzed intramolecular proton transfer reactions are possible and must be considered during the late stages of ESI to predict the site(s) of protonation and the ion's stability in the presence of solvent molecules.