Transformation of the gas‐phase favored O‐protomer of p‐aminobenzoic acid to its unfavored N‐protomer by ion activation in the presence of water vapor: An ion‐mobility mass spectrometry study

Abstract

An ion-mobility mass spectrometry study showed that the preferred O-protonated form of p-aminobenzoic in the gas phase can be converted to the thermodynamically less favored N-protomer by in-source collision-induced ion activation during the ion transfer process from the atmospheric region to the first vacuum region if the humidity is high in the ion source. Upon the addition of water vapor to the nitrogen gas used to promote the solid analyte to the gas phase under helium-plasma ionization conditions, the intensity of the ion-mobility arrival-time peak for the N-protomer increased dramatically. Evidently, the ion-activation process in the first vacuum region is able to provide the energy required to surmount the barrier to isomerize the O-protomer to the more energetic N-protomer. The transfer of the proton attached to the carbonyl oxygen atom of the O-protomer to the amino group takes place by a water-bridge mechanism. Apparently, the postionization transformations that take place during the transmission of ions from the atmospheric-pressure ion source to the detector, via different physical compartments of low to high vacuum, play an eminent role in determining the population ratios eventually manifested at the detector.

Selecting and identifying gas-phase protonation isomers of nicotineH+ using combined laser, ion mobility and mass spectrometry techniques

“…Not only are protomers isomers-and therefore unable to be mass-resolved by mass spectrometry-changes in ESI conditions are observed to affect relative protomer populations. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] This can be an analytical problem when protomers dissociate to different product ions under activation, a phenomenon that can confound assignment by comparison to reference spectra. Differences in the photodissociation of protomers have been used to assign protomer populations, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] although it is difficult to predict how the electronic spectroscopy and photodissociation will be affected by differences in protonation site.…”

“…For various ions, relative protomer populations have been obtained by comparing relative ion signal after separation using ion mobility mass spectrometry (IMS). 2,7,9,11,[42][43][44][45] The preponderance of these studies have employed classical drift-IMS (or closely related traveling-wave variants) that separate ions based on different collision-cross sections in a uniform electric field. In contrast, field asymmetric waveform ion mobility spectrometry (FAIMS) differs from drift-IMS in that, while drift-IMS typically separates ions depending on their ion mobility in the direction of ion flow, FAIMS separates species depending on both their high-and low-field ion mobility in fields applied orthogonal to the direction of ion transmission.…”

“…However, it has been shown that theoretical results cannot reliably predict the relative protomer populations generated by ESI. For example, protomer populations can be shifted by changing ESI conditions [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and less stable isomers can be kinetically trapped by the ESI process. 4,6,9,[47][48] Furthermore, the relative energies of protomers can depend strongly on different levels of theory and basis sets, which can result in the prediction of different lowest energy protomers using different computational approaches.…”

Effects of Residual Water in a Linear Quadrupole Ion Trap on the Protonation Sites of 4-Aminobenzoic Acid

“…2,6,13,19 ■ CONCLUSIONS In solution, 4-aminobenzoic acid is protonated on the amino nitrogen (N-protomer), whereas in the gas phase, the carboxylic acid oxygen (O-protomer) is the most basic site. 2,6,14,16,19 However, based on collision-activated dissociation experiments, both O-and N-protomers have been reported to be formed upon electrospray ionization, with their relative abundances depending on experimental conditions, including the solvent system used for ionization. 2,6,19 When acetonitrile−water was used as the ionization solvent, the solution N-protonation site was retained in the gas phase.…”

“…This finding was rationalized by evaporation of solvent molecules from the large solvent clusters (favoring N-protomer) initially formed around the N-protomer in the ion source area, resulting in the formation of smaller water and/or methanol clusters wherein the O-protomer is more stable than the N-protomer. 14,15,18,19 A methanol/water solvent "bridge" formed between the two protonation sites allows the proton to move from the N-to the O-protonation site. 14,15,18,19 This does not occur when acetonitrile is present as it forms stronger complexes with the N-protomer than water.…”