Year

2023

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

Molecules with multiple protonation sites pose a challenge to the assignment of analyte ions in mass spectrometry due to the formation of protonation isomers (protomers). This thesis provides insight on how to assign and manipulate protomer populations in atmospheric and low-pressure ion trap conditions.

The archetype protomer system—para-aminobenzoic acid (pABA)—is shown to react with a single methanol molecule and induces proton isomerism between the amino site to the carboxylic acid site. Unique protomer fragment ions are used to monitor methanol-catalyzed protomer interconversion. The second order rate constant is k2nd = (1.9 ± 0.1) × 10-11 cm3 molecule-1 s-1 and the linear rate response confirms one methanol molecule is involved. An accessible vehicle mechanism barrier (-10 kJ mol-1, DSDPBE-P86-D3(BJ)/aug-cc-pVDZ) and isotopic labelling support the proposed mechanism. This study sets the foundation to measure the kinetics of catalyzed internal proton transfer reactions.

Following this foundation study, reactions with pABA and water, formic acid, methanol, ethanol, propanol, ammonia, and acetonitrile are explored. Three cases are established. Acetonitrile forms stable adducts with pABA, owing to the strong ACN dipole moment (4.2 Debye). Vehicle mechanisms are implicated for formic acid, methanol, ethanol, propanol, and ammonia, over a broad range of reaction efficiencies (0.39—80%). Lowering the barrier led to an increase in reaction efficiencies and supports the implication of this barrier as the rate limiting step. Reactant proton affinities control the barrier height. A larger cluster size ([M+H]+(H2O)6) for water is found and is consistent with a proton shuttling pathway. This study shows that protomers can be tuned by carefully selecting the catalyst.

Methanol-mediated isomerism is investigated for ten arylamines in atmospheric pressure and ion trap conditions. Protomers are mobility separated and product fragments are assigned. Changes in fragment ratios are used to assign the methanol mediated proton transfer direction. Methanol isomerism kinetics in the low-pressure ion trap reproduces the atmospheric pressure isomerism direction, and reaction efficiencies are extracted (0.01—2.12 %). Isomerism direction is predicted by the protomer stabilities. Lowering the vehicle barriers increases the reaction efficiency, which is correlated with the proton affinity. The abstraction site is the most influential position to derivatize for barrier height control, rationalized by the charge-localized σ-framework. This study shows that, internal proton transfer catalysis reactions can be predicted for small molecules.

Ciprofloxacin—a model antibiotic—contains two protomers, the piperazinyl Nprotomer lose CO2 upon fragmentation, whereas the keto O-protomer loses H2O, exhibiting exclusive charge-driven and charge-remote fragmentation pathways. Atmospheric pressure methanol vapor reactions with both protomers reveal that proton transfer is unidirectional from the N-to-O-protomer, as predicted by thermodynamics (93 kJ mol-1, M06-2x/6-31G(2df,p)). Acetonitrile reacts with the N-protomer preferentially, depleting this protomer to form a stable ACN adduct, driven by the localized charge interaction. This study uses concepts from the small protomer systems and builds this up to a biologically relevant substrate.

This thesis established a new framework to rationalize how protomers influence the stability of gas-phase ions and shows how protomer populations can be tuned with confidence.

FoR codes (2020)

3406 Physical chemistry

Download

Share

COinS
 

Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.