Coordinated dissociative proton transfers of external proton and thiocarbamide hydrogen: MS experimental and theoretical studies on the fragmentation of protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate in gas phase

Article abstract of DOI:10.1016/j.ijms.2009.12.017

The dissociation chemistry of the protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate, PhCH{double bond, long}N{single bond}NHC({double bond, long}S)SCH₃, has been investigated by collision-induced dissociation (CID) mass spectrometry experiments in combination with density functional theory (DFT) calculations. Eliminations of H₂S, CH₃SH and (NSC)SCH₃ were the three fragmentation reactions observed in the tandem mass spectra, witnessed by the MS/MS analysis of native ³⁴S-isotopic ion and the D-labeling CID-MS experiment. Of the three fragmentations, both the added proton and the internal thiocarbamide hydrogen shift to the fragment ion (m/z 106) in the dissociation of losing (NSC)SCH₃, while both of them shift to the neutral fragment H₂S to generate the minor product ion at m/z 177. In the case of the feasible fragmentation process of CH₃SH elimination, one of the proton/the thiocarbamide hydrogen migrates to the fragment ion at m/z 163, and the other migrates to the neutral specie. Calculated results show that thiocarbamide sulfur (S5) is the most thermodynamically favored position for protonation. The mechanisms of these reactions were postulated according to the theoretical results, and the reaction energy profiles were also constructed. These results indicated that fragmentation of the protonated molecule was viewed as a result of the coordinated migration of both the external proton and the thiocarbamide hydrogen.

Full text of DOI:10.1016/j.ijms.2009.12.017

International Journal of Mass Spectrometry 291 (2010) 17–23
Contents lists available at ScienceDirect
International Journal of Mass Spectrometry
journal homepage: www.elsevier.com/locate/ijms
Coordinated dissociative proton transfers of external proton and thiocarbamide
hydrogen: MS experimental and theoretical studies on the fragmentation of
protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate in
gas phase
Kezhi Jianga,b, Gaofeng Bian , Nan Hu , Yuanjiang Pan , Guoqiao Lai
b
a
a,∗
b,∗∗
a
Department of Chemistry, Zhejiang University, Hangzhou, 310036, China
Key Laboratory of Organosilicon Chemistry and Material Technology, Hangzhou Normal University, Hangzhou, 310012, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 September 2009
Received in revised form
The dissociation chemistry of the protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate,
PhCH
N NHC( S)SCH3, has been investigated by collision-induced dissociation (CID) mass spectrom-
etry experiments in combination with density functional theory (DFT) calculations. Eliminations of H2S,
CH3SH and (NSC)SCH3 were the three fragmentation reactions observed in the tandem mass spectra,
2
4 December 2009
Accepted 24 December 2009
3
4
witnessed by the MS/MS analysis of native S-isotopic ion and the D-labeling CID-MS experiment. Of
the three fragmentations, both the added proton and the internal thiocarbamide hydrogen shift to the
fragment ion (m/z 106) in the dissociation of losing (NSC)SCH3, while both of them shift to the neutral
fragment H2S to generate the minor product ion at m/z 177. In the case of the feasible fragmentation
process of CH3SH elimination, one of the proton/the thiocarbamide hydrogen migrates to the fragment
ion at m/z 163, and the other migrates to the neutral specie. Calculated results show that thiocarbamide
sulfur (S5) is the most thermodynamically favored position for protonation. The mechanisms of these
reactions were postulated according to the theoretical results, and the reaction energy profiles were
also constructed. These results indicated that fragmentation of the protonated molecule was viewed as
a result of the coordinated migration of both the external proton and the thiocarbamide hydrogen.
Available online 13 January 2010
Keywords:
Coordinated dissociative proton transfers
Thioamide hydrogen
DFT
S-methylbenzenylmethylenehydrazine
Dithiocarboxylate
©
2010 Elsevier B.V. All rights reserved.
1
. Introductions
Tautomerism, however, can also take place in the neutral
compound in a reversible process through proton transfer (e.g.,
keto-enol, amide-iminol, thioamide-thioiminol, etc.) [20,21]. The
neutral thiocarbamide hydrogen of primary amines can also
precede gas phase elimination when heated and produce the cor-
responding isothiocyanate through transfer of the thiocarbamide
hydrogen [22–25]. In addition, amide position protons are wit-
nessed to behave mobility during CID of model peptides ions
by IRMPD spectrum [26]. Even some methylene hydrogen can
undergo migration to a reactive position prior to dissociation of
the precursor anions [27,28]. Therefore, in the case of protonated
thiocarbamide, an interesting question of dissociation mechanism
arises: can the thiocarbamide hydrogen also shift efficiently in the
protonated thiocarbamide? More importantly, between the added
proton and the thiocarbamide hydrogen, migration of which proton
results in the dissociation of the protonated compound?
A full understanding of the dissociation chemistry of a gas phase
ion is required for structural elucidation and has thus received
considerable attention [1–5], with the advent of tandem mass spec-
trometry (MS/MS) in combination with soft ionization techniques,
such as electrospray ionization (ESI) [6–8] and matrix-assisted laser
desorption (MALDI) [9,10]. Upon low energy collisional activation,
the protonated molecular ion isomerizes to produce many reac-
tive precursors through migration of the added proton to the less
favored protonation positions from the preferred one; it under-
goes fragmentation triggered by the ionizing proton, leading to the
“
mobile proton” model [13–19]. In the past decades, this “mobile
proton” model has been postulated to explain the dissociation of
both flexible peptides and rigid molecules in tandem mass spectra.
S-methyl substituted-methylene hydrazine dithiocarboxylate,
a derivative of thiocarbamide, is an important functional group of
many drug molecules which shows particular biological activities,
such as antibacterial and anticancer nature [29,30]. We recently
communicated that the transfer of the thiocarbamide hydrogen
leads to gas phase elimination in the neutral ketonic hydrazones
∗ Corresponding author at: Department of Chemistry, Zhejiang University, 38#,
Zheda Road, Hangzhou, Zhejiang, 310027, China.
∗
∗
Corresponding author.
E-mail address: panyuanjiang@zju.edu.cn (Y. Pan).
1
387-3806/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ijms.2009.12.017

1
8
K. Jiang et al. / International Journal of Mass Spectrometry 291 (2010) 17–23
Table 1
Product ions observed in the ESI-MS/MS spectra of the protonated compounds 1–10, at the normalization CID energy of 20%.
.
Compounds
R
Precursor ions [M+H]+ (relative abundance)
Relative abundances of product ions m/z (%)
1
2
3
4
5
6
7
8
9
H
211 (39.1%)
225 (23.6%)
241 (20.5%)
241 (35.8%)
241 (16.3%)
254 (76.1%)
225 (41.7%)
245 (63.2%)
289 (32.4%)
256 (100%)
177 (6.0%), 163 (100%), 106 (52.7%)
191 (4.2%), 177 (100%), 120 (42.8%)
207 (0.3%), 193 (100%), 136 (1.0%)
207 (8.2%), 193 (100%), 136 (87.7%)
207 (1.6%), 193 (100%), 136 (18.5%)
220 (0.2%), 206 (100%), 148 (1.6%)
195 (8.8%), 181 (100%), 124 (39.8%)
201 (4.6%), 197 (100%), 140 (29.2%)
255 (6.7%), 241 (100%), 184 (24.7%)
222 (1.3%), 208 (12.3%), 151 (1.4%)
p-CH3
o-OCH3
m-OCH3
p-OCH3
p-N(CH3)2
p-F
p-Cl
p-Br
p-NO2
10
from S-methyl dithiocarbazate [25]. In the present study, we select
S-methyl benzenylmethylene hydrazine dithiocarboxylate as a
model to carry out experimental and theoretical investigations on
the migration of the external proton and the internal thiocarbamide
hydrogen prior to fragmentation.
Hard data on geometries, electronic energies, as well as
entropies and free energies (at 298 K) of all structures considered
are available as Supporting Information. Potential energy hyper-
surfaces are presented using free energies at 298 K.
3. Results and discussion
3.1. Fragmentations in CID-MS
2
. Experimental
An abundant protonated molecular ion at m/z 211 was observed
Compounds 1–10 in Table 1, S-methyl arylmethylenehydrazine
in a full scan mass spectrum of S-methyl benzenylmethylene
hydrazine dithiocarboxylate (compound 1 in Table 1) under pos-
itive ion electrospray ionization conditions. As shown in Fig. 1a,
the protonated molecular ion underwent decomposition upon col-
lisional activation and generated two abundant product ions at m/z
dithiocarboxylate, ArCH
N NHC( S)SCH , were synthesized by
3
esterification of H NNHCS K, which was synthesized by reaction of
2
2
CS2 with H NNH ·H O and KOH in i-PrOH solvent, with dimethyl
2
2
2
sulfate, and then reacted with benzaldehydes to produce the corre-
sponding hydrazone [29,30] (Scheme 1S). The products were then
purified by wash with i-PrOH and recrystallization from CH Cl ,
1
63 and m/z 106, and a minor one at m/z 177. Protonated molecular
2
2
ions of its derivatives (compounds 2–10) had similar fragmentation
behaviors, with the same neutral losses of 34 Da, 48 Da and 105 Da,
respectively (Fig. 1S and Table 1), indicating that the fragmentation
reactions occurred at the thiocarbonate moiety in the CID process.
and identified by MS and NMR.
Analysis of the samples was operated on an LCQ advantage mass
spectrometer (ThermoFisher Company, USA), equipped with an ESI
ion source in the positive ionization mode, with data acquisition
using the Xcalibur software (Version 1.4). Typical parameters were
used for operation of the ESI-MS as follows [31–35].
The compounds were dissolved in methanol in the normal
collisional-induced dissociation (CID) experiment, while dissolved
in methanol-d4 in the D-labeling experiment. The solutions
were introduced into the source chamber via a length of 50 ␮m
Scheme 1 gave the plausible dissociation reactions of the
+
protonated compound
1
([M+H] ) at m/z 211 observed in
Fig. 1a. The fragment ion at m/z 106 is attributed to N-
+
protonated phenylmethanimine [PhCH NH ] , formed by losing
2
3
-(methylthio)-1,2-thiazirene (105 Da) from the molecular ion. The
most abundant fragment ion at m/z 163 in the CID spectrum is
assigned to be protonated N-isothiocyanato phenylmethanimine,
which was generated by the methanethiol elimination (48 Da) from
the precursor ion, meanwhile, the minor product ion at m/z 177 is
2-benzylidenehydrazono (methylthio)methenic cation, which cor-
−
1
i.d. × 190 ␮m o.d. used-silica tubing at a flow rate of 5 ␮L min
.
A potential of −4.5 kV, and a sheath gas of nitrogen at a pressure
of 25 bar were employed. The heated capillary was maintained at
◦
2
50 C. The collision-induced dissociation (CID) mass spectra were
obtained with helium as the collision gas after isolation of the pre-
cursor ions at the collision energy of 20%. More than 50 scans were
summed to produce a mass spectrum.
The theoretical calculations were performed with the Gaus-
sian 03 program [36]. The equilibrium geometries of reactants,
transition states, intermediates and products were optimized, by
using the density functional theory (DFT) method at the B3LYP/6-
3
1+G(d,p) level, with calculated force constants. No symmetry
constraint was imposed in the optimization. All reactants, interme-
diates and products were identified as true minima by the absence
of imaginary frequencies. Transition state (TS), on the other hand,
was identified by the presence of one single imaginary vibration
frequency and the normal vibrational mode. In addition, transition
states were confirmed by the intrinsic reaction coordinates (IRC)
calculations. Vibrational frequencies and zero-point energies (ZPE)
for all the key species were calculated at the same level of theory.
The DFT optimized structures were shown by Gauss View (Version
Scheme 1. Three different fragmentation reactions in CID of protonated compound
3
.09) software to give higher quality images of these structures.
1
.

K. Jiang et al. / International Journal of Mass Spectrometry 291 (2010) 17–23
19
Fig. 1. The MS/MS spectra of [M+H]+ ions of compound 1 ((a) C9H10N2S2 + H , (b) C9H10N2S S + H ) in the positive ESI mode.
+
34
+
uct ions at m/z 179 is formed via H232S elimination from isomer B.
The product ion [PhCH NH2]+ (m/z 106), however, has no sulfur
atom in the chemical formula, and thus no S isotopic ion peak is
observed in the CID spectrum.
Analysis of the fragment ions from Table 1 showed that both
the added proton and the internal thiocarbamide hydrogen precede
migration prior to or in the dissociation reactions. As can be seen,
both of them transfer to either the fragment ion at m/z 106 via
responds to the elimination of hydrogen sulfide from the precursor
ion.
34
These postulated decomposition reactions were confirmed by
3
4
the MS/MS analysis on the native
S isotopic ion. The sul-
fur element has two isotopes, 32S and 34S in nature, with the
relative abundance at 100% and 4.4%, respectively. As shown
in Fig. 2, decomposition of the mono isotope ion of MH at
+
m/z 211 produces the fragment ion [PhCH
N
NCS + H]+ at m/z
34
1
63 by losing CH SH. The first
S isotope ion at m/z 213,
the neutral loss of (NSC)SCH , or to the neutral fragment H S to
3
3
2
however, contains two isomeric structures due to the differ-
generate the minor product ion at m/z 177. In the most accessible
ent position of 3 S, [PhCH
4
N
NHC(
34 32
S) SCH + H] (A) and
3
+
reaction route of losing CH SH, one proton migrates to the fragment
3
3
2
34
+
+
[
PhCH
N
NHC(
S) SCH + H] (B). As expected, fragmentation
ion [PhCH
specie.
N
NCS + H] , while the other one shifts to the neutral
3
3
4
+
of isomer A gives the product ion at m/z 165, [PhCH
N NC S + H] ,
through the neutral loss of CH332SH; whereas dissociation of iso-
3
2
mer B results in the product ion at m/z 163, [PhCH
N
NC S + H]+
3.2. D-labeling CID experiments
via the neutral loss of CH334SH. The almost identical abundance
of the two product ions is attributed to the equal distribution of
To further investigate the migration of both the added proton
and the thiocarbamide hydrogen in the protonated ion, D-labeling
CID experiments were carried out. An abundant deuterated molec-
ular ion [M+D]+ at m/z 212 was generated by spraying the freshly
34
the S atom in nature. Interestingly, elimination of H S from the
2
isotopic ion at m/z 213 shows the similar fragmentation behaviors,
with nearly equivalent abundance of the isotopic fragment ions at
m/z 177 and m/z 179. The fragment ions at m/z 177 is generated by
the dissociation of isomer A through losing H234S, while the prod-
prepared methanol-d4 solution of compound 1 in positive mode.
+
Di-deuterated ion [MD –H] at m/z 213 was also formed from the
2
Fig. 2. The MS/MS spectra of [M+H]+ ions (a), [M+D]+ ions (b), and [M+2D–H]+ ion (c) of compound 1.

2
0
K. Jiang et al. / International Journal of Mass Spectrometry 291 (2010) 17–23
solution after some minutes. As displayed in Fig. 2, dissociation
result, N3 is the most unfavorable position for protonation of the
above three protonation sites, and the protonated ion MH-b1 is
much higher (85.6 kJ/mol) in free energy than MH-c1.
of the MD+ and [MD –H] show some different fragment ions to
+
2
+
+
those of MH . Fragment ion [PhCH NH ] contains both the exter-
2
nal proton and the thiocarbamide hydrogen from the precursor
Amide position protons in peptides have been witnessed to
undergo migration upon collisional activation by IRMPD spectrum
[28]. In structure MH-a1, the added proton is located at N2, and
the thiocarbamide-thioiminol tautomerism of the molecular ion
can proceed via 1,3-proton shift of the thiocarbamide hydrogen
(Scheme 2S) [21]. To undergo this 1,3-proton shift, it is required to
rotate the thiocarbonic group ( S5) to be trans to the thiocarbamide
hydrogen. The transition structure TS(a1–a2) for the rotation is
52.9 kJ/mol relative to the global minimum MH-c1, and the product
minimum MH-a2 is 28.5 kJ/mol higher in free energy than MH-c1.
The thiocarbamide hydrogen in MH-a2 can now be transferred to
S5, and MH-a2 isomerizes to MH-d1 via TS(a2–d1). The energy bar-
rier to this isomerization is 128.7 kJ/mol in free energy relative to
MH-c1, and the product minimum MH-d1 is only 2.5 kJ/mol higher
in free energy than the global minimum. The above results indicate
that transfer of the thiocarbamide hydrogen via thiocarbamide-
thioiminol tautomerism is also energetically accessible.
+
ion. As expected, the decomposition of [M+D] at m/z 212 gave
the corresponding fragment ion [PhCH NHD]+ at m/z 107, 1 Da in
+
molecular weight more than the analogous one from [M+H] . Simi-
+
larly, dissociation of [MD –H] (m/z 213) generated the product ion
2
+
[
PhCH ND ] at m/z 108, which lies 2 Da in molecular weight above
2
+
the analogous one from [M+H] . In comparison, the minor fragment
ion at m/z 177 has no added proton or the thiocarbamide hydro-
gen in the structure, because both of them transfer to the neutral
fragment H S in the fragmentation process. As a result, decompo-
2
+
sition of the protonated molecular ion [M+H] , the deuterated ion
[
M+D]+ and the di-deuterated ion [MD –H] resulted in the same
+
2
product ion at m/z 177 via the neutral loss of H S, HDS and D S,
2
2
respectively.
+
The most abundant fragment ion [PhCH
N NCS + H] , formed
by the CH SH elimination of the precursor ion, contains the
3
added proton (or the thiocarbamide hydrogen) in its structure. As
+
expected, fragmentation of the di-deuterated ion [MD –H] pro-
2
duced the [PhCH
N
NCS + D]+ ion at m/z 164, which is only 1 Da
more than the analogous product ion from [M+H] . Dissociation
.3.2. Fragmentation to form PhCH NH2+
3
+
The fragmentation route to generate PhCH NH2+ is viewed as a
+
of the deuterated ion [M+D] , however, generated two fragment
classical “mobile proton” model [11–19], in which both the added
proton and the thiocarbamide hydrogen are transferred to the frag-
ment ion and located at the N2 atom. Upon collisional activation of
the global minimum structure MH-c1, the added proton can be fea-
sibly transferred to a less stable site N2 atom to give MH-a1. Fig. 3
shows the reaction profile for the fragmentation of MH-a1 to gen-
ions, [PhCH
m/z 163 (Fig. 2b), with the neutral loss of CH SH and CH SD, respec-
N N
NCS + D]+ at m/z 164 and [PhCH NCS + H]+ at
3
3
tively. The more abundant ion at m/z 164 than that of m/z 163 in
the spectrum implied that it is more feasible for the thiocarbamide
hydrogen to shift to the methyl mercapto group, than the added
proton in the dissociative process.
◦
erate the product ion at m/z 106 in the terms of ꢀG 298, and the
◦
corresponding ꢀH 0 values are shown in parentheses.
3.3. Coordinated dissociative proton transfer
To precede this dissociation, it is necessary for the thiocar-
bamide group to rotate around the N2 N3 bond to form a
conformational isomer MH-a2, in which the N2 N3 bond is weak-
ened by breaking the conjugation of the lone electron pair on N3
to the C1 N2 double-bond, witnessed by lengthening the N2 N3
bond to 1.397 Å from 1.341 Å in MH-a1. The thiocarbamide hydro-
gen in MH-a2 is parallel to the ␲-electron orbit of N2 with the
Theoretical calculations were invoked to further investigate the
transfer of both the external and the internal thiocarbamide pro-
tons in the dissociation reactions of the protonated ion. The neutral
compound 1 can undergo thiocarbamide-thioiminol tautomerism
[
21] and exist as the thiocarbamide form in methanol solvent
according to the NMR results (Figs. 2S and 3S). Three main posi-
tions (N2, N3, and S5) in the thiocarbamide structure of compound
◦
dihedral angle ˚C1-N2-N3-H8 at −90.3 (Fig. 4S), indicating that it
is in an ideal position for the 1,2-proton migration of H8. The sub-
sequent breakage of the N2 N3 bond via TS-a2, triggered by the
formal charge on the external proton, occurs concomitantly with
migration of the hydrogen to the N2 atom, which leads to P-a1,
an ion-neutral complex of the phenylmethanimium ion (m/z 106)
1
potentially accommodate the “ionizing” proton to generate MH-a,
MH-b, and MH-c (Scheme 2S), respectively.
3
.3.1. Migration of the added proton and the thiocarbamide
hydrogen
Structure MH-c1 is at the global minimum on our calculated
and 3-(methylthio)-1,2-thiazirene (CH S(CSN)). Separation of P-a1
3
leads to the fragment ion at m/z 106, and combination of the prod-
ucts lies 69.9 kJ/mol in free energy above MH-c1. The calculated
energy barrier of the key step (TS-a2) is 169.4 kJ/mol in free energy
relative to the global minimum MH-c1, which is proximate to the
potential energy surface (PES), indicating that the thiocarbonyl
sulfur S5 is the most preferred site for protonation in the struc-
ture. The stability of MH-c1 is a consequence of the resonance
in the planar thiocarbonate structure, which disperses the pos-
itive charge to thiocarbamide nitrogen N3 and S6 (Scheme 3S).
Another structural contribution to the stability of MH-c1 is a long-
range hydrogen bond (S5-H· · ·N2) of 2.149 Å (Fig. 4S). In MH-c1,
the added proton on S5 can easily be transferred by taking advan-
tage of the S5-H· · ·N2 hydrogen bond to the N2 atom to generate
MH-a1. The energy barrier to this 1,4-proton shift via TS(c1-a1) is
◦
much small at 22.1 kJ/mol in terms of ꢀG 298, comparing to pro-
ton migration in protonated triglycine [13]. Structure MH-a1 is
also stabilized by resonance (Scheme 4S), by dispersing the pos-
itive charge to the phenyl ring. It lies slightly higher in free energy
than MH-c1 just by 3.3 kJ/mol. These results indicate that it is very
accessible for the migration of the external proton between S5
and N2.
Protonation at N3, however, formally localizes the charge on
the nitrogen atom in structure MH-b1, and even destroys the res-
onance of the thiocarbamic group and the hydrazonic moiety. As a
Fig. 3. Reaction profile for the fragmentation of the protonated compound 1 to the
phenylmethaniminium ion at m/z 106.

K. Jiang et al. / International Journal of Mass Spectrometry 291 (2010) 17–23
21
product minimum is P-a2, an ion-neutral complex of N2-pronated
N-isothiocyanato(phenyl) methanimine ion and CH SH, and sepa-
3
ration of P-a2 leads to the fragment ion at m/z 163. Combination of
the separated products lies 37.2 kJ/mol in free energy above MH-c1.
Analysis of the reaction profiles of Path 1 and Path 2 indi-
cates that the energy barriers of the CH SH elimination channels
3
is similar to dissociation of peptides [13–16], and is energeti-
cally more favorable than the dissociation channel to generate
the product ion PhCH NH2+
. The fragmentation channel of
Path 2 via TS-a1, however, shows kinetically and energetically
more feasible than Path 1, with relative smaller energy bar-
rier and lower free energy of the products, which is consistent
with the D-labeling CID result. As a consequence, migration of
the thiocarbamide hydrogen, rather than the added proton to
Fig. 4. Reaction profile for the most feasible fragmentation process of CH3SH elim-
ination, triggered by migration of the external proton.
fragmentation of the b2 to the a1 ion for triglycine (163.9 kJ/mol,
the methyl mercapto group occurs in the CH SH elimination,
3
3
9.3 kcal/mol) [14], indicating a feasible fragmentation channel.
albeit the two channels co-exist in the fragmentation reac-
tion.
3
.3.3. Fragmentation with CH SH elimination
3
Methanethiol elimination is the most favorable pathway
3
.3.4. Fragmentation with H S elimination
2
in the decomposition of the protonated S-methyl substituted-
benzenylmethylene hydrazine dithiocarboxylate, according to the
CID-MS experimental results in Table 1. The D-labeling CID-MS
experiment also indicated that the dissociative proton transfer of
the added proton competes with that of the thiocarbamide pro-
ton in this process. We communicated that the neutral analogs can
The mechanistic route for H S elimination has also been investi-
2
gated as shown in Fig. 6. Due to resonance stabilization (Scheme 3S),
some of positive charge in structure MH-c1 is delocalized to thio-
carbamide N3, and then the thiocarbamide hydrogen H7 behaves
partially as an ionizing proton. Amide position protons have also
been witnessed by IRMPD spectrum to behave mobility during CID
of peptides ions [26]. Transfer of H7 in MH-c1 to S6 atom pro-
duces an isomeric ion MH-e1, which is 122.3 kJ/mol higher in free
energy than MH-c1. The energy barrier to this proton transfer via
TS(c1–e1) is 162.6 kJ/mol in free energy, which is 21.1 kJ/mol higher
than that in Path 2. Protonation at the S6 atom in MH-e1, however,
undergo CH SH elimination when heated in the gas phase, trig-
3
gered by the migration of the thiocarbamide hydrogen [25]. This
paper provides two of the most feasible mechanistic decomposi-
tion routes, triggered by the transfer of the added proton and the
thiocarbamide hydrogen, respectively.
Fig. 4 displays the mechanistic reaction profile (Path-1) for
does not directly lead to CH SH elimination to give the fragment
3
CH SH elimination, in which the external proton is transferred to
3
ion at m/z 163, with the length of 1.816 Å for the C4 S6 bond. The
energy barrier to this fragmentation via TS-e1 is 169.3 kJ/mol higher
in free energy relative to MH-c1, which is even kinetically more
unfavorable than the Path 1 via TS-c2.
A conformational isomerization of MH-e1 to MH-e2 by rotation
of the C4 S6 bond can be feasibly carried out, with an energy barrier
of 15.3 kJ/mol relative to MH-e1. In MH-e2, the proton on the S6
atom is now in an ideal position to be transferred upon collisional
activation to the S5 atom. The energy barrier to this 1,3-proton
transfer via TS-e2 is 212.5 kJ/mol in free energy relative to MH-
c1, and the product minimum P-e2 is inclined to form the final
the methyl mercapto sulfur (S6) from the thiocarbonyl sulfur (S5).
To proceed this dissociation, it is necessary to rotate the mercapto
group to be trans to the methyl mercapto group via TS(c1–c2),
which lies only 43.1 kJ/mol in free energy above MH-c1. In the
resulting isomer MH-c2, which is 12.3 kJ/mol higher in free energy
than MH-c1, the migrating external proton is in an ideal position for
◦
transfer, with the dihedral angle ˚H-S5-C4-S6 at −175.2 (Fig. 5S).
The subsequent 1,3-proton shift in the structure MH-c2 proceeds,
and generates a loose ion-neutral complex, P-c2, with a long ion-
neutral bond C4 S6 of 2.080 Å. The barrier to the proton transfer via
TS-c2 is 158.4 kJ/mol relative to MH-c1, and P-c2 lies 112.5 kJ/mol
above MH-c1. Decomposition of the loose complex to the product
ion at m/z 163 is exoergic by 0.4 kJ/mol and the separated products
lies 112.1 kJ/mol in free energy above MH-c1.
product ion at m/z 177 by losing H S, with exoergic by 57.6 kJ/mol.
2
Combination of the separated products is 77.0 kJ/mol higher in free
energy than MH-c1.
Analysis of the above calculation results show that there is
an decreasing order in the calculated energy barrier to the three
An alternative efficient mechanistic route (Path-2, Fig. 5)
involves the migration of the thiocarbamide hydrogen to the
methyl mercapto sulfur (S6). Prior to fragmentation, the external
proton can easily be transferred from S5 to N2 to give the structure
fragmentation reactions of losing H S, CH S(CSN) and CH SH, indi-
2
3
3
cating an increasing kinetically favorable order in reaction, which is
in accordance with the increasing order in the relative abundance
of the corresponding fragment ion the CID-MS spectra (Table 1).
MH-a1. The subsequent dissociation of MH-a1 occurs with CH SH
3
elimination by transferring H8 to the methyl mercapto S6 via TS-
a1, which is higher in free energy than MH-c1 by 141.4 kJ/mol. The
Fig. 5. Reaction profile for the most feasible fragmentation process of CH3SH elim-
ination, triggered by migration of the thiocarbamide hydrogen.
Fig. 6. Reaction profile for the fragmentation of MH-c1 by losing H2S.

2
2
K. Jiang et al. / International Journal of Mass Spectrometry 291 (2010) 17–23
Dissociation of H S has a much considerable energy barrier and
the C4 S5 bond. The above results indicated that fragmentation of
the protonated molecule is a result of the coordinated migration of
both the external proton and the thiocarbamide hydrogen.
2
therefore the minor fragment ion (m/z 177, 6.0%) in the CID-MS.
These results validate the rationality of the postulated mechanistic
fragmentation channels and also indicate that the dissociation reac-
tions of the protonated title compound are kinetically controlled in
the process of CID.
Acknowledgments
The CID-MS experimental results have substantiated that
both the added proton and the internal thiocarbamide hydrogen
undergo migration prior to or in the dissociation reactions. Theo-
retical investigation of the mechanistic routes also indicates both
the external proton and the thiocarbamide hydrogen play different
roles in the three fragmentation reactions. In the process of los-
The Ministry of Education of China for Grant NCET-06-0520 and
the National Science Foundation of Zhejiang Province for Grant
Z206510 support this work.
Appendix A. Supplementary data
ing CH S(CSN), the external (mobile) proton migrates to the imine
3
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ijms.2009.12.017.
N2 from the most favorable protonation site S5, and triggers the
breakage of the N2 N3 bond, concomitantly with migration of the
thiocarbamide hydrogen to imine N2 to form the fragment ion at
m/z 106. The fragmentation of losing CH SH is induced by migration
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