Formation of Protonated ortho-Quinonimide from ortho-Iodoaniline in the Gas Phase by a Molecular-Oxygen-Mediated, ortho-Isomer-Specific Fragmentation Mechanism

Article abstract of DOI:10.1021/jasms.9b00108

Upon collisional activation under mass spectrometric conditions, protonated 2-, 3-, and 4-iodoanilines lose an iodine radical to generate primarily dehydroanilinium radical cations (m/z 93), which are the distonic counterparts of the conventional molecula

Full text of DOI:10.1021/jasms.9b00108

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Formation of Protonated ortho-Quinonimide from ortho-Iodoaniline
in the Gas Phase by a Molecular-Oxygen-Mediated, ortho-Isomer-
Specific Fragmentation Mechanism
Ramu Errabelli, Zhaoyu Zheng, and Athula B. Attygalle*
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ABSTRACT: Upon collisional activation under mass spectrometric
conditions, protonated 2-, 3-, and 4-iodoanilines lose an iodine radical
to generate primarily dehydroanilinium radical cations (m/z 93), which
are the distonic counterparts of the conventional molecular ion of aniline.
When briefly accumulated in the Trap region of a Triwave cell in a
SYNAPT G2 instrument, before being released for ion-mobility
separation, these dehydroanilinium cations react readily with traces of
oxygen present in the mobility gas to form peroxyl radical cations.
Although all three isomeric dehydroanilinium ions showed avid affinity for
O2, their reactivities were distinctly different. For example, the product-ion
spectra recorded from mass-selected m/z 93 ion from 3- and 4-
iodoanilines showed a peak at m/z 125 for the respective peroxylbenze-
naminium ion. In contrast, an analogous peak at m/z 125 was absent in
the spectrum of the 2-dehydroanilinium ion generated from 2-iodoaniline.
Evidently, the 2-peroxylbenzenaminium ion generated from the 2-dehydroanilinium ion immediately loses a •OH to form
protonated ortho-quinonimide (m/z 108).
KEYWORDS: ortho effect, distonic ions, dehydroanilinium radical cations, dioxygen, quinonimide
dissociation (ECD) or electron-transfer dissociation (ETD)
conditions,38 to radical anions generated from iodotyrosine
residues,39 to organometallic cobalt(III) and aluminum(III)
complexes40,41 and other inorganic ions.42,43
INTRODUCTION
■
Reactions between gaseous ions and neutral molecules have
been investigated from the early stages of mass spectrome-
try.1−3 Many examples have been documented of adventitious
or deliberate ion−molecule reactions (IMR) that occur
between residual neutral gas molecules and nontargeted or
mass-selected ions.4−16 Such ion−molecule reactions are often
useful as probes for molecular structure and functional group
determinations.17−21 Some of these reactions have been
particularly useful for the differentiation of isomeric radical
ions.22−24 Ion−molecule reactions are usually investigated
using ion-storing mass analyzers such as ion traps and Fourier-
transform ion cyclotron resonance instruments.24 Occasionally,
the formation of ion−molecule reaction adducts have also been
observed on tandem-in-space instruments as well.16,25,26
One of the fundamentally interesting ion−molecule
reactions that has been investigated is the deliberate, or
sometimes undesired, addition of dioxygen to radical sites of
distonic radical cations.16,27−31 For example, both pyridine-
and aniline-derived distonic radical cations are known to form
peroxyl radical cations with molecular oxygen.23,32 Similar O2
addition reactions have been reported also for several distonic
radical anions.33−37 Moreover, molecular oxygen is known to
add to radical ions formed by the cleavage of N−C α bonds of
the amide backbone in peptides under electron-capture
The term distonic ion was originally coined by Radom and
co-workers to describe radical cations originating (formally) by
ionization of zwitterions.44 However, the term distonic ion is
more commonly used simply to denote ions with formally
separated charge and radical centers.44−53 Such ions are of
fundamental interest because of the different chemical
activities that can take place at two distinct loci within the
same species. Kenttamaa and her co-workers54 showed that 2-,
̈
3-, and 4-dehydroanilinium ions, which are distonic isomers of
the aniline radical cation (the molecular ion), can be formed in
the gas phase from the respective iodoanilines. These isomers
are kinetically stable and sufficiently long-lived to be
investigated separately. They can be distinguished from the
Received: November 25, 2019
Revised: February 18, 2020
Accepted: February 20, 2020
Published: February 20, 2020
©
XXXX American Society for Mass
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Spectrometry. Published by the
American Chemical Society. All rights
reserved.
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Figure 1. A schematic diagram of Waters Synapt-G2 HDMS instrument.
isomeric nondistonic radical cation by an ion−molecule
reaction because only the three dehydroanilinium ions react
by abstracting a thiomethyl radical from dimethyl disulfide.54,55
In a recent study, Hossain et al.56 reported the formation of
deprotonated quinonoidal imides under electrospray ionization
conditions. In the present work, we report the formation of
ortho-quinonimide from protonated ortho-iodoaniline in the
gas phase by a molecular-oxygen-mediated, ortho-isomer-
specific fragmentation mechanism.
pusher before they were mass-separated by the time-of-flight
(TOF) analyzer.
The m/z 220 ion generated under ESI conditions, from 100-
ppm o-, m-, or p-iodoaniline in acetonitrile:water (50:50 v/v;
flow rate 20 μL/min), was mass selected and subjected to ion-
mobility separation under the following instrumental con-
ditions: Trap collision energy, 4−28 eV; Transfer collision
energy, 2−28 eV; IMS wave velocity, 1500 m/s; IMS wave
height, 40.0 V; IMS (N2) gas flow 140 mL/min; scroll pump
pressure, 4.34 mbar; source pressure, 3.43 × 10−3 mbar;
helium cell pressure, 1.40 × 103 mbar; IMS cell pressure, 3.98
mbar (N2 supplied from a nitrogen generator); TOF analyzer
pressure, 8.36 × 10−7 mbar; Trap-cell pressure, 3.10 × 10−2
mbar (Ar); Transfer-cell pressure, 3.38 × 10−2 mbar (Ar).
Unless otherwise stated, the general ESI source conditions
for most experiments were as follows: capillary voltage, 2.85
kV; sampling cone, 30.0 V; extraction cone, 3.0 V; desolvation-
gas flow rate, 138 L/h; sample infusion flow rate, 20 μL/min;
Vernier-probe adjuster position, 5.92 mm. The source and
desolvation-gas heater temperatures were held at 80 and 100
°C, respectively.
For specificity experiments, o-, m-, or p-iodoaniline solutions
(100-ppm in 50:50 acetonitrile:water) were electrosprayed at a
capillary voltage of 2.85 kV and a cone voltage of 65 V. The in-
source-generated m/z 93 ions were mass selected by the
quadrupole and subjected to ion mobility separation under low
collision-energy settings (Trap 4 eV and Transfer 2 eV).
Similarly, chronograms were recorded using a dual-spray ESI
system (with the baffel plate removed), and the intensities of
m/z 93 and 125 ions were monitored on two separate
channels. The mass selection by the quadrupole was switched
from m/z 93 to m/z 125 every 1.024 s. The ToF analyzer was
set to monitor ions between m/z 20−1500. Initially a 100-ppm
solution of aniline in 50:50 acetonitrile:water was nebulized
continuously via the main electrospray probe at a rate of 20
μL/min (Figure 1). A high sampling-cone voltage (70 V) was
used to generate m/z 93 radical cations from the aniline
solution. At 2.0 min, a 10-μL aliquot of a p-iodoaniline solution
(100 ppm in 50:50 acetonitrile:water) was introduced via the
lock-spray probe at a rate of 20 μL/min. The baffle plate,
which mechanically blocks the signal from one sprayer while
the instrument is recording the signal from the other, was
removed for this experiment. Other instrumental parameters
were: sampling cone voltage 70 V; main probe capillary voltage
EXPERIMENTAL SECTION
■
Materials. Acetonitrile (ACN) was purchased from
Pharmco-Aaper Co. (Brook field, CT). Other chemicals,
including o-iodoaniline, m-iodoaniline, p-iodoaniline, and
deuteriated water (D2O) were purchased from Sigma-Aldrich
Chemical Co. (St. Louis, MO) and used without further
purification. Deionized water was obtained from a Milli-Q
purification system (Millipore Corporation, U.S.A.). Solutions
of all samples (100 ppm) were prepared in a mixture of 50:50
acetonitrile:water. p-Iodo[15N]aniline was prepared by adding
iodine (10.0 mg, 0.078 mmol) to a solution of [15N]aniline
(8.0 mg, 0.08 mmol) and sodium bicarbonate (11.0 mg, 0.13
mmol) in water (0.5 mL) at 0 °C.57 The mixture was stirred at
room temperature for 1 h, and the black precipitate was filtered
and washed with water to obtain the desired product [1H
NMR spectroscopy confirmed 1,4 substitution (400 MHz,
CDCl3) δ; 6.47 (d, 2H, J = 8.0 Hz), 7.41 (d, 2H, J = 8.0 Hz);
Isomeric purity 96% (based on GC-MS); 70 eV EI-MS, 220
(M+•, 100), 127 (15), 93 (75)].
Mass Spectrometry. All experiments were conducted on a
Synapt G2 HDMS (Waters, MA) mass spectrometer equipped
with an ESI source (Figure 1). House nitrogen generated by a
Parker-Balston model 75-A74 nitrogen generation system
(Haverhill, MA, U.S.A.) was used as the nebulizer, desolvation,
and cone gases. Mass calibration (m/z 20−1500) was
performed using a solution of sodium formate (100 ppm).
Mass spectra were acquired in the positive-ion mode over a
range of m/z 20−1500. For ion-mobility experiments, the ions
of interest were mass selected by the quadrupole analyzer (Q)
and transferred to the Triwave cell. Mass-selected ions were
briefly accumulated in the Trap region of the Triwave cell and
released to the N2-filled traveling wave ion-mobility cell, via a
short chamber of helium. After the ion-mobility separation, the
ions passed the Transfer cell and underwent acceleration by the
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3.85 kV; lock-spray probe capillary voltage 2.50 kV; source and
desolvation heater temperatures 80 and 100 °C, respectively;
cone and desolvation gas flows 34 and 138 L/h, respectively.
Density Functional Theory (DFT) Calculations. DFT
calculations were carried out using the Gaussian 09W program
at the B3LYP level of theory with a 6-311++G (2d,2p) basis
set for C, H, N, O, and LanL2DZ basis set for iodine.
Complete geometry optimizations were conducted for all
species with subsequent frequency calculations for species at
ambient pressure (1 atm) and room temperature (298.15 K)
to verify the nature of each stationary state on the potential
energy surface. In brief, reactants and products were associated
with all positive vibrational frequencies, whereas transition
states (TS) were associated with only one imaginary frequency,
for which the normal vibrational mode corresponds to the
expected bond formation/breaking movements in a specific
reaction pathway. Atom coordinates and absolute energies of
intermediates and transition states obtained in this way are
provided as Supporting Information.
respectively), the arrival-time distributions (ATDs) and mass
spectra recorded for each species showed only one peak in
both arrival-time and mass spectral profiles, establishing that
under such low ion-activation conditions, the m/z 220 ions
from none of the three isomers undergo any noticeable
fragmentation (Figure 2 insets).
However, the product-ion spectra of the three mobility-
separated isomers, recorded after subjecting them to 25 eV
collisional activation in the Transfer-collision cell, were
dominated by a peak at m/z 93 (Figure 3). In fact, these
RESULTS AND DISCUSSION
■
Under ESI-MS conditions ortho-, meta-, and para-iodoanilines
generate intense signals at m/z 220 for their respective
protonated species.58 The m/z 220 ions generated in the ion
source by ESI from each isomer were mass selected by the
quadrupole filter on a Synapt G2 HDMS instrument and
subjected to ion-mobility separation using nitrogen as the
mobility gas. The recorded arrival-time profiles showed that
the ion generated from the ortho isomer manifests a slightly
faster mobility than the other two species (Figure 2). When the
ion-activation conditions in the Trap and Transfer collision
regions of the Triwave cell were relatively low (4 and 2 eV,
Figure 3. m/z 20−250 region of product-ion spectra (m/z 20 to
1500) recorded from mass-selected and ion-mobility separated m/z
220 ions generated from ortho- (a), meta- (b), and para-iodoaniline
(c) activated at 4 eV Trap and 25 eV Transfer collision-energy
settings. The mobilograms corresponding to each isomer are shown in
insets. All other experimental conditions were identical to those given
in Figure 2.
spectra were indistinguishable from the product-ion spectra
recorded from mass-selected m/z 220 ions by subjecting them
to 10 eV activation in the transfer-collision cell but without
subjecting them to ion-mobility separation (i.e., in the absence
of helium or nitrogen in the mobility cell) (Figure 4).
The presence of the base peak at m/z 93 confirmed that the
major fragmentation of all three isomers represents the loss of
an iodine radical due to the homolytic fragmentation of the
C−I bond (Scheme 1). The C−I bond fragmentation
generates the respective dehydroanilinium ions as noted
54
̈
previously by Chyall and Kenttamaa.
The homolytic fragmentation of the C−I bond in
iodoanilinium ions can easily be attained also in the Trap-
collision cell of the Triwave system. From such an experiment,
we expected to see two well-separated peaks in the ion-
mobility arrival-time profiles: one peak for the precursor m/z
220 ion and another for the m/z 93, the major product-ion
generated by collision-induced fragmentation in the Trap
region. However, to our surprise, in the mobilograms recorded
from meta and para-iodoaniline at a Trap-collision energy
setting of 28 eV, a very significant, but entirely unexpected,
additional peak was observed in the 4.80−4.95 ms region
(Figure 5b,c).
From the mass spectra corresponding to the peaks at 5.89
and 3.53 ms peaks in the mobility profile of the para isomer
(and 5.68 and 3.53 ms peaks in the profile of the meta isomer;
Figure 5b), it was evident that these two peaks represent the
m/z 220 precursor ion and the m/z 93 product ion, generated
Figure 2. Ion mobility arrival-time distributions of m/z 220 ions of
protonated ortho- (a), meta- (b), and para-iodoaniline (c). Insets
show the m/z 20 to 250 region of product-ion mass spectra (m/z 20
to 1500) recorded at Trap and Transfer collision-energy settings of 4
and 2 eV, respectively. The m/z 220 ions were generated by ESI from
100-ppm solutions in acetonitrile:water (50:50) of each iodoaniline.
Other conditions: sampling cone voltage 30 V, capillary voltage 2.85
kV; source and desolvation temperatures 80 and 100 °C, respectively;
cone and desolvation gas flows 38 and 138 L/h, respectively. Ion-
mobility separations were carried out at a wave velocity of 1500 m/s
and a wave height of 40.0 V and using N2 as the buffer gas at a flow
rate of 140 mL/min.
C
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Figure 4. Transfer-fragmentation product-ion spectra recorded under
nonmobility conditions (no helium or nitrogen in the mobility cell,
and no ion accumulation in the Trap region) from mass-selected m/z
220 ions generated under ESI conditions from protonated ortho- (a),
meta- (b), and para-iodoaniline (c). Samples were infused as 100-ppm
solutions in acetonitrile:water (50:50), and data were acquired for 0.5
min. The spectra displayed were generated by coadding and averaging
for the whole acquisition period. The sampling cone voltage was 30 V;
capillary voltage was 2.85 kV; source and desolvation heater
temperatures were 80 and 100 °C; and cone- and desolvation-gas
flows were 38 L/h and 138 L/h, respectively. Trap and Transfer
collision energies were 4 and 10 eV, respectively.
Figure 5. Arrival-time distributions (ATDs) recorded from the mass-
selected m/z 220 ion of o-iodoaniline (a), m-iodoaniline (b), and p-
iodoaniline (c) at a Trap-collision energy setting of 28 eV. Insets
show spectra that represent ions delivered to the ToF analyzer at
specific arrival times. Ions were generated by electrospraying 100-ppm
solutions in 50:50 acetonitrile:water at a flow rate of 20 μL/min.
Other experimental conditions were as follows: sampling-cone voltage
30 V; capillary voltage 2.85 kV; source and desolvation temperatures
80 and 100 °C, respectively; cone and desolvation gas flow rates were
38 and 138 L/h, respectively; Transfer-collision energy of 2.0 eV. IM
separations were carried out at a wave velocity of 1500 m/s, a wave
height 40.0 V, and a mobility gas (N2) flow rate of 140 mL/min.
Scheme 1. Homolytic Fragmentations Manifested by
Protonated Iodoanilines upon Collision-Induced
Dissociation (CID)
precursor ion. The coadded spectra generated from the mass-
selected m/z 221 (M+H)+ ion from protonated p-iodo[15N]-
aniline showed the corresponding O2-adduct peak at m/z 126
(Supporting Information Figure S1A). Moreover, the averaged
spectrum obtained from deuteronated p-iodoaniline [I−
+
C6H4−ND3 ] showed the corresponding peak at m/z 128
(Supporting Information Figure S1B). An analogous adduct
peak at m/z 125 for the oxygen adduct was observed also in
the spectrum recorded from the adduct of meta-iodoaniline
(Figure 5b). All these results confirmed that the dehydroani-
linium radical ions from meta and para isomers form adducts
with dioxygen under the experimental conditions used.
Apparently, the addition reaction takes place at the radical
site of the distonic ion, with minimal direct involvement of the
charge-bearing amino group. The formation of such an adduct
was not surprising because the addition of dioxygen to phenyl-
radical distonic ions has been well documented.31,36,58−60 For
example, a small peak for an oxygen adduct has been seen in
the product-ion spectrum recorded from 4-iodoanilinium ion
subjected to photodissociation at 260 nm.59 In the present
work, we observed the formation of such adducts under certain
tandem mass spectrometric conditions. Although dehydroani-
linium ions show a very high reactivity toward molecular
oxygen, no peaks corresponding to such adducts were observed
when the mobility cell was not engulfed with nitrogen
(Supporting Information Figure S2). Presumably, nitrogen
from the relatively high-pressure mobility cell compartment
(about 3−4 mbar) leaks out to the low-pressure ion-trapping
region (about 10−2 mbar) (Figure 1). Oxygen present in trace
amounts in the nitrogen then reacts with the Trap-
accumulated dehydroanilinium ions. If the addition took
place in the mobility cell, the arrival-time peaks were expected
be broader and diffused in shape. However, the peaks observed
in the Trap (Figure 5c). In contrast, the product-ion spectrum
corresponding to the 4.92 ms peak in Figure 5c showed three
peaks at m/z 125, 109, and 93. The accurate mass of the m/z
125 ion confirmed its molecular formula to be C6H7NO2
(Supporting Information Table S1). It was evident that this
peak represented an ion produced by the addition of molecular
oxygen to the distonic m/z 93 radical cation that was generated
in the Trap by a homolytic removal of iodine from the m/z 220
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for adducts were symmetrical and nearly Gaussian (Figure
5b,c). Furthermore, product-ion spectra recorded from Trap-
fragmented mass-isolated m/z 220 ions, but without nitrogen
in the mobility cell, did not show a peak at m/z 125 or at m/z
108 (Supporting Information Figure S2). This result was not
surprising because ions are not accumulated in the Trap
region, but transmitted continuously, when the instrument is
not operated under mobility conditions. In contrast, ion
packets are accumulated for about 200 μs in the Trap region
before they are released for separation under mobility
conditions. Thus, there is a sufficient amount of time for
ion−molecule reactions to take place in the Trap region when
mobility experiments are conducted.
Compared to the arrival-time profiles recorded from
protonated meta- and para-aniline that acquired from
protonated o-iodoaniline was very different (Figure 5). At
first glance, it was surprising that an m/z 125 peak in the 4.6−
5.0 ms region for a dioxygen adduct was not visible in the
arrival-time profile recorded from the mass-selected m/z 220
ion from o-iodoaniline (Figure 5a). It appeared as if the
dehydroanilinium radical cation generated from the ortho
isomer does not form a dioxygen adduct. On the other hand,
we noticed that the shape of the 3.60 ms peak was now rather
skewed, and the spectra corresponding to the tailing end of the
peak showed a signal at m/z 108, in addition to that at m/z 93
(Figure 5a). A rigorous scrutiny conducted by extracting ion-
intensity profiles for m/z 108 and 93 ions deconvoluted the
3.60 ms profile to two peaks with respective maxima at 3.81
and 3.53 ms (Figure 6). Thus, the 3.60 ms peak is a composite
representing an m/z 108 ion in addition to the expected m/z
93 species (Figure 6c).
Figure 6. Arrival-time distributions (ATDs) recorded from the mass-
selected m/z 220 ion of o- iodoaniline (c) and from extracted ion
profiles of m/z 93 (a) and m/z 108 (b). Profiles were recorded at a
Trap-collision energy setting of 28 eV. Insets show spectra
representing ions delivered to the ToF analyzer at specific arrival
times. Ions were generated by electrospraying 100-ppm solutions in
50:50 acetonitrile:water at a flow rate of 20 μL/min. Other
experimental conditions were as follows: sampling-cone voltage 30
V; capillary voltage 2.85 kV; source and desolvation temperatures 80
and 100 °C, respectively; cone and desolvation gas flow 38 and 138
L/h, respectively; Transfer-collision energy 2.0 eV. IM separations
were carried out at a wave velocity of 1500 m/s, wave height of 40.0
V, and a mobility gas (N2) flow rate of 140 mL/min.
Evidently, the addition of dioxygen to the ortho-dehydroa-
nilinium ion follows a different route compared with those
taken by meta- and para-dehydroanilinium ions. To rationalize
the formation of the ortho-isomer-specific m/z 108 ion, we
propose the fragmentation mechanism illustrated in Scheme 2.
Calculated electronic energies predicted that the 2-perox-
ylbenzenaminium ion formed by the initial interaction of
dioxygen with the ortho-dehydroanilinium ion is a short-lived
species. The energy released (176.4 kJ/mol) in the exergonic
formation of the initial adduct far exceeds that required to
surmount the small 2.8 kJ/mol energy barrier separating the 2-
peroxylbenzenaminium ion (7) from the final products (9)
(Figure 7). Consequently, the adduct 7 (m/z 125)
immediately eliminates a hydroxyl radical via a six-membered
transition state (TS7−8) and forms protonated ortho-
quinonimide (m/z 108) as the final product. Thus, neither a
peak at m/z 125 nor m/z 109 (for a 16-Da oxygen atom loss
from the m/z 125 ion) is visible in the spectrum of ortho-
dehydroanilinium ion: the hypothetical cleavage of the peroxyl
bond in adduct 7 to form the m/z 109 ion (11) requires 139.8
kJ/mol (Figure 7; 7 → 11), whereas the ejection of HO• needs
only to surmount a 2.8 kJ/mol energy barrier to form the o-
quinonimide cation (9, m/z 108) (Figure 7; 7 → 9). A loss of
HO• from oxygen adducts of cation radicals formed from
protonated peptides has been noted previously by Xia et al.38
The proposed mechanism of a HO• removal by an ortho-
isomer specific mechanism (Scheme 2) resembles the charge-
remote pathway proposed by Moore et al. for the formation of
an ortho-quinone derivative from the peroxyl radical generated
by the tyrosinyl radical cation combining with oxygen.39
Prendergast et al.61 reported a similar HO• loss by a charge-
remote mechanism from the oxygen adduct of 5-(N,N,N-
Scheme 2. Proposed Fragmentation Pathway for the
Formation of Protonated ortho-Quinonimide (9; m/z 108)
from ortho-Dehydroanilinium Ion (6)
trimethylammonium)-2-methylphenyl radical cation, forming a
charged quinone methide derivative. The same researchers
described the formation of an ammonium tagged o-
benzoquinone derivative from 5-ammonium-2-hydroxyphenyl
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Figure 7. Combined relative electronic and zero-point energies [in kJ/mol computed for 0 K by the density functional theory method B3LYP using
a 6-311+ + G(2d,2p) basis set] and molecular structures of energy-optimized ions and transition states associated with the formation of m/z 108
(9) and 109 (11) ions upon O2 addition to o-dehydroanilinium radical anion (6).
radical.62 In contrast to the aforementioned charge-remote
mechanisms, the pathway described in Scheme 2 denotes a
transfer from a charge-bearing functionality resulting in the
formation of protonated ortho-quinonimide (9). This is
supported by the observation that the adduct of the
deuteronated 2-dehydro[N2H2]anilinium radical cation (for
which a peak was not observed), loses a DO• to generate an
ion of m/z 110 (Supporting Information Figure S3).
Quinonimides are structurally interesting molecules. Pre-
viously, the o-quinonimide anion has been generated from o-
azidophenol and examined by photoelectron spectroscopy.56
In this study, we have demonstrated the formation of
protonated o-quinonimide under positive-ion-generating elec-
trospray ionization and Triwave ion-mobility tandem mass
spectrometric conditions.
The addition reactions of O2 to meta- and para-
dehydroanilinium radical cations are also exergonic (Support-
ing Information Figure S4 and S5). Thus, the formation of the
m/z 125 ion is expected to be spontaneous. However, the
dissociation of 3- and 4-peroxylbenzenaminium ions (m/z
125) to form m/z 109 ions by losing a 16-Da oxygen atom are
highly endergonic reactions (Supporting Information Figures
S1, S3, S4, and S5). Thus, it is not surprising that the
intensities of the peaks at m/z 109 ions for the oxygen-atom
loss are very low. Furthermore, this results is congruent with
the observation that in the potential energy surfaces (PES) that
describe the energies of the interaction of molecular oxygen
with meta- and para-dehydroanilinium ions, the 3- and 4-
peroxylbenzenaminium ions occupy minima (Supporting
Information S4 and S5). In contrast, the 2-peroxylbenzenami-
nium ion formed from the ortho-dehydroanilinium ion has a
more favorable alternative reaction channel available (Figure
7). Thus, the m/z 125 ion for the oxygen adduct of the 2-
dehydroanilinium cation continues to undergo fragmentation
via the low-energy saddle point TS7−8 by a HO• elimination
(instead of losing an O• as that followed by its meta and para
counterparts) and forms the ortho-quinonimide (m/z 108)
(Figure 7, 9).
To demonstrate the specificity of the O2-addition reaction,
we generated the m/z 93 ions by subjecting protonated o-, m-,
and p-iodoaniline to collision-induced dissociation in the low-
vacuum region of the ion source (Figure 1), by increasing the
sampling-cone voltage to 65 V (Supporting Information Figure
S6). The m/z 93 ions generated in the ion source in this way
were mass-selected by the quadrupole analyzer and subjected
to ion mobility separation under low collision activation
conditions (Trap 4 eV and Transfer 2 eV). The arrival-time
profiles recorded from meta- and para-dehydroanilinium
radical cations showed peaks for the respective 3-peroxylben-
zenaminium and 4-peroxylbenzenaminium ions (m/z 125) in
addition to those for the precursor m/z 93 ions (Supporting
Figure S6b,c). However, the peaks for adduct ions were very
small compared to those obtained from trap fragmentation of
m/z 220 ions (Figure 5b,c). Apparently, the 3 and 4-
dehydroanilinium ions generated in the source are mostly
quenched in the source by atmospheric oxygen. Thus, the
peaks at 4.97 and 5.04 ms in Supporting Figure S6b,c represent
the adducts formed from small amounts 3 and 4-
dehydroanilinium ions that had survived the onslaught of
oxygen in the source. In other words, we believe that the peaks
depicting m/z 93 ions in Figure 5 represent the conventional
radical cation of aniline (formed by isomerization), which is
nonreactive toward oxygen. This proposition is supported by
the observation that the product-ion spectra of m/z 93 ions
recorded at high transfer-collision energy (20 eV) showed a
product ion peak at m/z 66 for a 27-Da HCN loss (Supporting
Information Figure S7a and S7b). On the other hand,
dehydroanilinium ions are expected to give a product ion
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Research Article
peak at m/z 76 for a 17-Da NH3 loss. Furthermore, a peak for
the m/z 125 adduct was absent in the arrival-time profile
recorded from 2-dehydroanilinium ion (Supporting Informa-
tion Figure S6a). It appears that the 2-dehydroanilinium ion is
so reactive that it undergoes complete annihilation in the ion
source. The higher reactivity of the 2-dehydroanilinium ion
compared to that of the 3- or 4-dehydroanilinium ion has been
noted recently by Kelly et al.24 Thus, the m/z 93 ion delivered
from the ion source to the mobility cell is the nonreactive
molecular radical-cation of aniline (Supporting Information
Figure S6a).
Further support for the above supposition was obtained
from the data recorded using a dual-sprayer ionization source
hyphenated to the mass spectrometer. The results confirmed
that the oxygen addition reaction in fact can take place in the
ion source under ambient conditions. To demonstrate this, an
experiment was set up to specifically monitor the intensities of
the m/z 93 and 125 ions on two channels (Supporting
Information Figure S8a,b). Initially, the m/z 93 ion was
generated continuously in the ion source by electrospraying a
100-ppm solution of aniline at a high sampling-cone voltage.
Under such high cone-voltage conditions, in addition to the
m/z 94 ion for protonated aniline, a small abundance of the
conventional m/z 93 ion is also generated in the ion source.63
The m/z 93 ion generated in this way is deemed to be a
composite consisting primarily of the molecular ion of aniline,
which known to be inert to oxygen addition (Supporting
Information Figures S7a,b). Thus, intensity of the m/z 125 ion
in the ion source was initially low. While continuously spraying
the solution of aniline from the main spray probe, a sample of
p-iodoaniline was introduced at 2.0 min to the source via the
secondary sprayer for 15 s. Immediately after the p-iodoaniline
was introduced, the intensity of the m/z 125 signal soared up,
confirming the formation the O2-adduct from the in-source
generated 4-dehydroanilinium ion generated by the collision-
induced fragmentation of protonated 4-iodoaniline in the ion
source (Supporting Information Figure S8b).
AUTHOR INFORMATION
■
Corresponding Author
Athula B. Attygalle − Center for Mass Spectrometry,
Department of Chemistry, and Chemical Biology, Stevens
Institute of Technology, Hoboken, New Jersey 07030, United
States; orcid.org/0000-0002-5847-2794; Email: aattygal@
stevens.edu
Authors
Ramu Errabelli − Center for Mass Spectrometry, Department of
Chemistry, and Chemical Biology, Stevens Institute of
Technology, Hoboken, New Jersey 07030, United States
Zhaoyu Zheng − Center for Mass Spectrometry, Department of
Chemistry, and Chemical Biology, Stevens Institute of
Technology, Hoboken, New Jersey 07030, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/jasms.9b00108
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by funds provided by the Stevens
Institute of Technology (Hoboken, NJ). We thank Julius
Pavlov for his comments on the manuscript.
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CONCLUSIONS
■
Undesired ion−molecule reactions lead to the formation of
ions that cannot be formed directly from the precursor ions.
Such reactions complicate mass spectra and not only distort
quantification results obtained by multiple reaction monitoring
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ASSOCIATED CONTENT
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The Supporting Information is available free of charge at
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Figures and tables showing additional mass spectral, ion
mobility, and computational data.
(PDF)
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