Deprotonation effect of tetrahydrofuran-2-carbonitrile buffer gas dopant in ion mobility spectrometry

Rationale When dopants are introduced into the buffer gas of an ion mobility spectrometer, spectra are simplified due to charge competition. Methods We used electrospray ionization to inject tetrahydrofuran‐2‐carbonitrile (F, 2‐furonitrile or 2‐furancarbonitrile) as a buffer gas dopant into an ion mobility spectrometer coupled to a quadrupole mass spectrometer. Density functional theory was used for theoretical calculations of dopant‐ion interaction energies and proton affinities, using the hybrid functional X3LYP/6‐311++(d,p) with the Gaussian 09 program that accounts for the basis set superposition error; analytes structures and theoretical calculations with Gaussian were used to explain the behavior of the analytes upon interaction with F. Results When F was used as a dopant at concentrations below 1.5 mmol m–3 in the buffer gas, ions were not observed for α‐amino acids due to charge competition with the dopant; this deprotonation capability arises from the production of a dimer with a high formation energy that stabilized the positive charge and created steric hindrance that deterred the equilibrium with analyte ions. F could not completely strip other compounds of their charge because they either showed steric hindrance at the charge site that deterred the approach of the dopant (2,4‐lutidine, and DTBP), formed intramolecular bonds that stabilized the positive charge (atenolol), had high proton affinity (2,4‐lutidine, DTBP, valinol and atenolol), or were inherently ionic (tetraalkylammonium ions). Conclusions This selective deprotonation suggests the use of F to simplify spectra of complex mixtures in ion mobility and mass spectrometry in metabolomics, proteomics and other studies that generate complex spectra with thousands of peaks. Copyright © 2016 John Wiley & Sons, Ltd.