B American Society for Mass Spectrometry, 2017 J. Am. Soc. Mass Spectrom. (2017) 28:2580Y2587
Untrapping Kinetically Trapped Ions: The Role of Water
Vapor and Ion-Source Activation Conditions
on the Gas-Phase Protomer Ratio of Benzocaine Revealed
by Ion-Mobility Mass Spectrometry
Hanxue Xia, Athula B. Attygalle
Center for Mass Spectrometry, Department of Biomedical Engineering, Chemistry, and Biological Sciences, Stevens Institute of
Technology, Hoboken, NJ 07030, USA
Abstract. The role of water vapor in transforming the thermodynamically preferred
species of protonated benzocaine to the less favored protomer was investigated
using helium-plasma ionization (HePI) in conjunction with ion-mobility mass spec-
trometry (IM-MS). The IM arrival-time distribution (ATD) recorded from a neat benzo-
caine sample desorbed to the gas phase by a stream of dry nitrogen and ionized by
HePI showed essentially one peak for the O-protonated species. However, when
water vapor was introduced to the enclosed ion source, within a span of about 150 ms
the ATD profile changed completely to one dominated by the N-protonated species.
Under spray-based ionization conditions, the nature and composition of the solvents
have been postulated to play a decisive role in defining the manifested protomer
ratios. In reality, the solvent vapors present in the ion source (particularly the ambient humidity) indirectly dictate
the gas-phase ratio of the protomers. Evidently, the gas-phase protomer ratio established at the confinement of
the ions is readjusted by the ion-activation that takes place during the transmission of ions to the vacuum.
Although it has been repeatedly stated that ions can retain a Bmemory^ of their solution structures because they
can be kinetically trapped, and thereby represent their solution-based stabilities, we show that the initial airborne
ions can undergo significant transformations in the transit through the intermediate vacuum zones between the
ion source and the mass detector. In this context, we demonstrate that the kinetically trapped N-protomer of
benzocaine can be untrapped by reducing the humidity of the enclosed ion source.
Keywords: Kinetic-trapping, Benzocaine, Protomers, Ion mobility, Helium-plasma ionization, HePI
Received: 3 August 2017/Revised: 25 August 2017/Accepted: 30 August 2017/Published Online: 21 September 2017
he protonation of molecules that contain multiple basic
sites has been the focus of extensive studies [1–19].
Prototropic isomers formed by protonation at different loci in
a molecule are known as protomers. Results from many studies
confirm that different protomers (or deprotomers) of the same
molecule can coexist in the gas phase [20–25]. Recently,
different ion-mobility-dispersion methods have been used to
separate protomers, prior to subjecting them to mass spectro-
metric (MS) or infrared (IR) detection [5, 17, 26–29].
In a recent study, Warnke et al.  provided conclusive
evidence that different protomeric populations of benzo-
caine, a widely used local anesthetic, can coexist in the gas
phase. From their investigations, based on ion-mobility tech-
niques combined with IR and MS, they concluded that the
immediate environment of benzocaine has a profound influ-
ence on the ratio of the N-andO-protomers manifested in the
gas phase. They attributed the presence of the N-protomer to
kinetic trapping of the solution-phase structure during trans-
fer into the experimental setup , and concluded that the
electric properties of the surrounding medium are the main
determinant for the preferred protonation site that enables
the kinetic trapping.
Electronic supplementary material The online version of this article (https://
doi.org/10.1007/s13361-017-1806-9) contains supplementary material, which
is available to authorized users.
Correspondence to: Athula Attygalle; e-mail: email@example.com