Characterizing the Tautomers of Protonated Aniline Using Differential Mobility Spectrometry and Mass Spectrometry

Abstract

The site of protonation for gas-phase aniline has been debated for many years, with many research groups contributing experimental and computational evidence for either the amino-protonated or the para-carbon-protonated tautomer as the gas-phase global minimum structure. Here, we employ differential mobility spectrometry (DMS) and mass spectrometry (MS) to separate and characterize the amino-protonated (N-protonated) and para-carbon-protonated ( p-protonated) tautomers of aniline. We demonstrate that upon electrospray ionization (ESI), aniline is protonated predominantly at the amino position. Similar analyses are conducted on another three isotopically labeled forms of aniline to confirm our structural assignments. We observe a significant reduction of the relative population of the p-protonated tautomer when a protic ESI solvent is employed (methanol/water) compared to when an aprotic solvent (acetonitrile) is employed. We also observe conversion of the p-protonated species into the N-protonated species upon clustering with protic solvent vapor post-DMS selection-a finding supported by previous experimental data acquired using DMS-MS.

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

“…In fact, Lapthorn et al 31 and Wang et al 32 have reported that spectral profiles do change when structural changes happen in precursor ions due to changes in source conditions. 15,32 For example, Walker et al 33 recently published a fragmentation spectrum of protonated aniline that is significantly different from those reported previously. 17,34 In the current study, we have shown that quantitative differences in peak intensity ratios occur when different prototropic tautomers are formed due to changes in humidity in ambient-pressure ion sources.…”

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.…”

“…FAIMS has proven to be a powerful tool for separating and analysing protomer populations at atmospheric pressure prior to detection by mass spectrometry. 1,4,6,8,46 Relative-energy calculations are typically coupled with FAIMS analysis to rationalise experimental results. However, it has been shown that theoretical results cannot reliably predict the relative protomer populations generated by ESI.…”

“…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.…”

Gas‐phase protomers of p‐(dimethylamino)chalcone investigated by travelling‐wave ion mobility mass spectrometry (TWIMS)

“…The sites of gas‐phase protonation (or deprotonation) of molecules have been the subject of many investigations . Even molecules as simple as carbon monoxide are known to protonate in different ways .…”