J. Phys. Chem. B 2001, 105, 12399-12409
12399
Collision-Induced Dissociation of the Ag+-Proline Complex: Fragmentation Pathways and
Reaction MechanismssA Synergy between Experiment and Theory
Tamer Shoeib, Alan C. Hopkinson, and K. W. Michael Siu*
Department of Chemistry and Centre for Research in Mass Spectrometry,
York UniVersity, Toronto, Ontario, Canada, M3J 1P3
ReceiVed: June 19, 2001; In Final Form: September 25, 2001
Gas-phase collision-induced dissociation of the Ag+-proline complex shows six major product ions. Tandem
mass spectrometry reveals that at least three of the fragment ions are formed directly from the complex.
These are a cyclic immonium ion, formed after elimination of AgH from the Ag+-proline complex, another
cyclic immonium ion formed after the elimination of both AgH and CO2, and finally an ion formed as the
product of a reductive-elimination reaction in which H2 is lost as a neutral. Selective and nonselective deuterium
labeling experiments and hybrid density functional calculations have been employed to probe fragmentation
mechanisms that account for all experimental results. The mechanisms for the competitive losses of AgH and
H2 from the Ag+-proline complex have been calculated at B3LYP/DZVP.
Introduction
Metal ions play an important role in biological systems.
Interactions between metal ions and peptides or proteins are
common and stimulate the latter to carry out their regulatory
functions.1 In solution, metal ions are known to influence the
three-dimensional structures of nucleic acids.2-5 Studies of the
solution-phase chemistries of transition metals then not only
provide valuable insights into biological processes such as
enzymatic redox reactions,6 oxidation, dioxygen transport and
electron transfer,7,8 but also further our understanding of
heterogeneous catalysis and organometallic reactions.
Gas-phase studies, on the other hand, provide the opportunity
to probe metal-ligand interactions in the absence of the
stabilization effects afforded by a solvent.9-27 This, in turn,
allows for a more detailed study of the metal-ion binding site.
Thermodynamic properties obtained from experimental gasphase studies, for example binding energies, are often compared
with those calculated by theoretical means; many gas phase
experimental studies have been successfully complemented by
ab initio molecular orbital calculations.28-35
Amino acid complexes of transition metal ions were first
observed and studied using fast atom bombardment (FAB).36,37
However, the limited solubility of metal salts and poor sensitivity
did not encourage the widespread, systematic study of these
complexes. Sensitivity is not typically an issue in matrix-assisted
laser desorption/ionization (MALDI),38-39 but the fragmentation
yield from metastable ions produced by this technique are often
poor. As the fragment ions give information on atom connectivity and hence structure of the precursor, MALDI is therefore
less than ideal for studying fragmentation pathways. One
technique that has proven effective for the study of metalcontaining amino acids and peptides and the one employed here
is electrospray tandem mass spectrometry. Electrospray ionization40 is a technique that is known to be a soft ionization method
and one that is efficient at producing gas-phase metal containing
ions,41-47 whose solubility in water or water/methanol is
* To whom correspondence should be addressed. Tel: (416)650-8021.
Fax: (416)736-5936. E-mail: [email protected].
typically high. Also, fragmentation is efficient and is easily
controlled via collision-induced dissociation, a process in which
energy is crucial in determining fragmentation products and their
yield.
Silver (I) binds strongly to peptides in the gas phase.48-53
The fragmentation of such argentinated complexes has been
demonstrated to be effective for gas-phase peptide sequencing.54
Recent density functional molecular orbital studies have shown
that Ag+ can be mono-, di-, or tricoordinate in complexes with
R-amino acids;55 tetracoordinated Ag+ has been postulated for
relatively small peptides.34,56a The binding of silver(I) to glycine,
diglycine and triglycine and to a number of other polypeptides
has been investigated.34,56a In particular, the structures of
argentinated glycine and its oligomers have been examined in
detail by means of density functional theory.56a The structures
were found to fall into three major categories: (a) fivemembered cyclic structures in which the silver ion is dicoordinated by the amino nitrogen and the carbonyl oxygen atom
of the first residue; (b) multiple ring structures in which the
silver ion is chelated by three or four atoms; and (c) silver salts
in which the silver ion is bound to the carboxylate anion of the
zwitterionic amino acid or peptide. Structures (a) and (b) have
been described as “charge-solvated” as the amino acid or peptide
effectively solvate the silver ion in the gas phase.
Proline is an unusual amino acid in that it is the only naturally
occurring amino acid with a secondary R-amino group, a feature
that makes it more basic than many other R-amino acids. As
silver ion affinities of amino groups are lower than their
corresponding proton ion affinities but follow the same relative
order, the larger binding energy of the secondary amine helps
to stabilize the silver-salt structure of proline (structure 1) in
the gas phase, making it about 2 kcal mol-1 lower in energy
than the charge-solvated form of the complex (structure 2) in
the gas phase.55 By contrast, the lowest energy form of the Cu+proline complex is the charge-solvated form.56b This difference
between Ag+ and Cu+ binding to COO- goups was previously
observed56a and was attributed to the inability of Cu+ to form
two strong bonds to the COO- group.56a Proline plays a critical
10.1021/jp012335o CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/13/2001
12400 J. Phys. Chem. B, Vol. 105, No. 49, 2001
Shoeib et al.
Figure 1. Positive ion mode electrospray mass spectrum of a solution of 1mM proline and 0.1 mM AgNO3 in 1:1 (v/v) H2O/CH3OH.
Figure 2. Collision-induced dissociation of (a)
107Ag+-proline,
(b)
109Ag+-proline
and (c)
109Ag+-d
2-proline.
Dissociation of the Ag+-Proline Complex
J. Phys. Chem. B, Vol. 105, No. 49, 2001 12401
Figure 3. Energy-resolved collision-induced dissociation of
107Ag+-proline.
Figure 4. Collision-induced dissociation of the [M - H2 +
107Ag]+
ion of the
107Ag+-proline
complex.
12402 J. Phys. Chem. B, Vol. 105, No. 49, 2001
Shoeib et al.
SCHEME 1: Upper Numbers are Enthalpies, Lower (italicized) Numbers are Free Energies. Numbers Calculated at
B3LYP/DZVP and are Quoted at 298 K and are in kcal mol-1. Bold Numbers are Structure Numbers, Bold Italicized
Values are Nominal m/z Values Assuming the Lighter Isotopes. Numbers in Parentheses are Relative Free Energies of
Isomers
role in protein conformation and is frequently found in the turns
of folded protein chains.57-61
In this paper, we provide a detailed study of the collisioninduced dissociation products of the Ag+-proline complex. We
also postulate mechanisms for the dissociation reactions; these
are supported by the results of deuterium labeling experiments
and by DFT calculations.
Experimental Section
Materials. Stock solutions were prepared by separately
dissolving 2-3 mg of proline (99% Aldrich 17,182-4) and 2-3
mg of AgNO3 (99.8% Sigma S-0139) each in 1 mL of H2O.
Sample solutions were typically 1 mM in proline and 0.1 mM
in AgNO3 in a mixture of 1:1 (v/v) H2O/CH3OH. Deionized
water and reagent grade methanol (Aldrich) were used as
solvents. Deuterium exchange experiments were carried out in
solutions that contain deuterium oxide (99.9%D CDN isotopes)
and CH3OD (99.5%D Aldrich 15,193-9) instead of water and
methanol. Selective deuterium labeling experiments were performed using D/L proline-2-d1 (98.9%D CDN isotopes G144P1).
Mass Spectrometry. Experiments were performed on an API
3000 prototype and an API III; both are AB SCIEX (Concord,
Ontario) triple-quadrupole mass spectrometers. Sample solutions
were continuously infused at a rate of 4 µL min-1 into the
pneumatically assisted electrospray probe using dry air as the
nebulizer gas. Mass spectra were obtained in the positive ion
detection mode with unit mass resolution at a step size of 0.1
m/z unit and a dwell time of 10 ms/step. Typically, 10 scans
were summed to produce a mass spectrum. Product and
precursor ion spectra were obtained with nitrogen (argon in the
case of the API III) being the collision gas at a pressure of about
3 mTorr. For the acquisition of product ion spectra center-ofmass collision energies (Ecm) in the range of 0.5-5 eV were
employed; for precursor ion spectra laboratory collision energies
(Elab) between 5 and 45 eV were typically used. Pseudo MS3
was accomplished by raising the orifice bias potential to induce
Dissociation of the Ag+-Proline Complex
J. Phys. Chem. B, Vol. 105, No. 49, 2001 12403
SCHEME 2: Upper Numbers are Enthalpies, Lower (italicized) Numbers are Free Energies. Numbers Calculated at
B3LYP/DZVP and are Quoted at 298 K and are in kcal mol-1. Bold Numbers are Structure Numbers, Bold Italicized
Values are Nominal m/z Values Assuming the Lighter Isotopes. Numbers in Parentheses are Relative Free Energies of
Isomers
fragmentation in the lens region, mass selecting the appropriate
product ion in Q1, inducing its fragmentation in q2, and mass
analyzing the second generation product ions in Q3.
Computational Methods
Molecular orbital calculations were performed using Gaussian
98.62 All structures were optimized without symmetry constraints
by density functional theory (DFT) using the B3LYP hybrid
method63-68 and the DZVP basis set.69,70 All critical points were
characterized by harmonic frequency calculations and were
shown to be at minima. The two minima associated with each
transition structure were established by intrinsic reaction
coordinate calculations.71
Results and Discussion
Electrospraying proline in the presence of silver(I) produced
abundant proline-containing ions (Figure 1). Next to protonated
proline (m/z 116), argentinated proline ions (m/z 222 and 224,
corresponding to [M + 107Ag]+ and [M + 109Ag]+ (M )
proline), respectively) are the most abundant ions. Sodiated
proline (m/z 138) is also abundant, sodium being an ubiquitous
contaminant in water and methanol. The fragmentation pattern
of Ag+-proline is illustrated in Figure 2. Unambiguous assignment of the peaks can be made by comparing the product ion
spectra of proline and d2-proline (proline with its -NH- and
-COOH hydrogens replaced by deuterium atoms) complexing
with the two silver isotopes. Among the differences between
the dissociation of 107Ag+-proline (Figure 2a) and the dissociation of 109Ag+-proline (Figure 2b) are the 2-m/z-unit differences
between the peaks at m/z 220 (Figure 2a) and m/z 222 (Figure
2b), m/z 107 (Figure 2a) and m/z 109 (Figure 2b), corresponding
to the presence of different isotopes of Ag in the two spectra;
the peaks are thus assigned as [M - H2 + Ag]+ and Ag+,
respectively. The apparent anomaly of observing a peak at m/z
109 in Figure 2a, will be addressed later. The ion at m/z 114 is
common to both Figure 2a and b, and cannot be due to an ion
containing silver, it is assigned as [M - AgH]+. The loss of
neutral AgH has previously been observed by Grewal et al.33
and the mechanism of its formation was described in detail.
A comparison of Figure 2b and c provides information on
the number of acidic (exchangeable) hydrogen atoms contained
within the product ions. From this comparison, it is apparent
that the ions at m/z 68 and 96 must contain no exchangeable
hydrogen atoms, those at m/z 70 and 222 must contain one
exchangeable hydrogen, and the [M - AgH]+ at m/z 114 (Figure
2b) and at m/z 116 (Figure 2c) must contain two exchangeable
hydrogens atoms.
The variation of branching ratios as a function of collision
energy is shown in Figure 3. From these energy-resolved CID
12404 J. Phys. Chem. B, Vol. 105, No. 49, 2001
Figure 5. Precursor ion spectra of m/z 96: (a) 9.0 eV and (b) 22.4 eV collision energy.
Figure 6. Precursor ion spectra of m/z 70: (a) 22.0 eV and (b) 36.0 eV collision energy.
Shoeib et al.
Dissociation of the Ag+-Proline Complex
J. Phys. Chem. B, Vol. 105, No. 49, 2001 12405
Figure 7. Precursor ion spectra of m/z 68: (a) 13.5 eV, (b) 20.0 eV and (c) 26.9 eV collision energy.
experiments it is apparent that H2 loss to form [M - H2 + Ag]+
and AgH loss to form [M - AgH]+ predominate at relatively
low collision energies. At higher collision energies, these ions
appear, in turn, to dissociate and produce other ions, including
Ag+, m/z 68, m/z 70, and m/z 96. These secondary dissociation
reactions were confirmed by pseudo MS3 experiments, in which
the primary dissociation products, i.e., the [M - H2 + Ag]+
and [M - AgH]+ ions, were formed via collision-induced
dissociation reactions in the lens region (“source”) of the mass
spectrometer, mass-isolated, and fragmented in q2.
The results for [M - H2 + 107Ag]+ are displayed in Figure
4. It is evident that the fragment ions, m/z 107 and 68, are
abundant. Also of note are the ions at m/z 176 and 112, which
are apparently formed via the loss of CO2 and 107AgH,
respectively. The facile formation of [M - H2 + Ag]+ from
[M + Ag]+ is apparently the reason for observing 109Ag+ in
Figure 2a. Most of the ions at m/z 222, mass-selected for CID,
were [M + 107Ag]+; however, a small fraction was [M - H2 +
109Ag]+, which had been formed in the lens region.
The dissociation pathways to m/z 68, 70, and 96 are
substantiated in Figures 5-7. Figure 5 shows the precursor ion
spectra of m/z 96 at two collision energies: (a) 9 eV (for singly
charged precursors) and (b) 22.4 eV. It is evident that at the
lower collision energy, the source of m/z 96 is fragmentation
of [M - AgH]+; at the higher collision energy, [M + Ag]+
becomes a source. Taken collectively, the results strongly
suggest that [M + Ag]+ dissociates first to give [M - AgH]+,
which then dissociates to yield m/z 96 after the loss of H2O.
The precursor ion spectra of m/z 70 are shown in Figure 6.
At the lower collision energy of 22 eV (assuming singly charged
precursors, Figure 6a), the only abundant source of m/z 70 is
protonated proline at m/z 116. It is only at the relatively high
collision energy of 36 eV that argentinated proline ions appear
to fragment directly to yield m/z 70 with concomitant loss of
apparently AgH and CO2.
Figure 7 shows three precursor ion spectra of the ion at m/z
68. At the lowest collision energy of 13.5 eV (Figure 7a) the
ion [M - AgH]+ is observed as the only precursor ion. At the
higher collision energy of 20 eV (Figure 7b) ions [M + Ag]+
(m/z 222 and 224) appear at relatively high abundance, while
ions [M + H2O + Ag]+ (m/z 240 and 242) and [M - AgH]+
(m/z 114) are at lower abundance. From the fragmentation of
[M - H2 + 107Ag]+ (Figure 4), it is evident that the ion at m/z
68 is a product of the dissociation of [M - H2 + 107Ag]+ (via
the elimination of CO2 and 107AgH). A close inspection of
Figure 7 shows an ion at m/z 220, which is [M - H2 + 107Ag]+; its corresponding [M - H2 + 109Ag]+ at m/z 222 is
isobaric with [M + 107Ag]+. Judging from the relative abundance of m/z 220, 222 and 224, the [M + Ag]+ ions are more
abundant than the [M - H2 + Ag]+ ions. It is also important to
note that only at the highest collision energy of 26.9 eV, (Figure
7c), the presence of the ion at m/z 70 as a precursor of the ion
at m/z 68 is observed. Taken collectively, the evidence strongly
suggests that the ion at m/z 68 is likely a product of several
dissociation pathways, including those that have [M - AgH]+,
[M - H2 + Ag]+ and the ion at m/z 70 as intermediates. It is
apparent from Figure 7 that the fragmentation of [M - H2 +
Ag]+ to produce m/z 68 is a significantly higher energy process
than the fragmentation of [M - AgH]+ to produce the same
ion, and that the loss of H2 from m/z 70 to produce m/z 68 is
the highest energy process.
Schemes 1 and 2 present plausible reaction mechanisms, that
account for all the data presented here. In Scheme 1, the two
forms of the [M + Ag]+ complex, the silver salt form 1 where
12406 J. Phys. Chem. B, Vol. 105, No. 49, 2001
Figure 8. Collision-induced dissociation of (a)
107Ag+-2-d
Shoeib et al.
1-proline
and (b)
Ag+ is coordinated to the carboxylate of zwitterionic proline,
and the Ag-solvated form 2 where the Ag+ is coordinated to
the amino nitrogen and the carbonyl oxygen of classical
(nonzwitterionic) proline, are given. It is well-known that amino
acids exist as zwitterions in crystals and in aqueous solutions.
In the gas phase, however, the absence of solvating intermolecular interactions generally renders zwitterions less stable than
the classical form. In fact, it has been shown that zwitterionic
glycine in the gas phase is not even at a critical point on that
potential energy surface. The addition of a metal ion, however,
is known to stabilize the zwitterionic form of amino acids
relative to their classical forms.56a In the former, the resulting
product may be viewed as a protonated metal salt, whereas in
the latter, the product is a metal solvation complex.56a
The extent of this stabilization is amino acid dependent and
appears to correlate with the basicity of the amino acids. In
this study, we find that for proline the silver salt form 1 is lower
in free energy than the Ag-solvated form 2 by 2.2 kcal mol-1.
This result is to be compared with that for glycine where the
silver salt form is higher in free energy than the silver solvation
complex form by 5.3 kcal mol-1.56a
The salt form of [M + Ag]+ can lose H2 or HD (see Figure
2) by means of reductive elimination to form ion [M - H2 +
Ag]+ through paths 1 and 2 (see Scheme 1); reaction enthalpies
and free energies for path 1, are 23.1 and 14.1 kcal mol-1 and
for path 2, 19.5 and 10.1 kcal mol-1. This salt structure, 1, can
also undergo a simple rearrangement to the Ag-solvated form
of [M + Ag]+, 2, from which two possible pathways for H2 or
HD elimination (paths 3 and 4) thus leading to two different
isomers of [M - H2 + Ag]+. The enthalpies and free energies
of these reactions are 16.6 and 8.0 kcal mol-1 for path 3, and
17.4 and 8.4 kcal mol-1 for path 4, respectively. The relative
109Ag+-2-d
1-proline.
free energies of the four isomers of [M - H2 + Ag]+ show
structure 5 generated from path 3 to be the most energetically
favorable, whereas structures 4 and 6 generated from paths 2
and 4 are nearly equally energetically favorable with relative
free energies being 0.2 and 0.4 kcal mol-1, respectively, higher
than structure 5. Structure 3 generated from path 1 is higher on
the [M - H2 + Ag]+ energy surface; this isomer is 4.1 kcal
mol-1 higher in free energy than 5. It is noteworthy that every
[M - H2 + Ag]+ isomer depicted in Scheme 1 contains only
one exchangeable hydrogen; this is in agreement with Figure 2
which shows a 1-m/z difference between the [M - H2 + 109Ag]+ and the [M* - H2 + 109Ag]+ ions. Isomers 5 and 6 of
[M - H2 + Ag]+ are postulated to form structure 7 via the loss
of AgH and CO2; structure 7 has an m/z of 68 and contains no
H/D-exchangeable hydrogen atoms. This hypothesis is in
accordance with experimental data shown in Figures 2 and 4,
the latter of which shows not only the presence of ion 7, but
that of the intermediates resulting from the loss of CO2 (m/z
176) and 107AgH (m/z 112) from [M - H2 + 107Ag]+. The
reaction enthalpy and free energy for the dissociation of ion 5
to ion 7, via the loss of AgH and CO2, are 82.2 and 60.8 kcal
mol-1, respectively. These values are comparable to the reaction
enthalpy of 81.4 and free energy of 60.5 kcal mol-1 for the
analogous dissociation of ion 6. These relatively high reaction
enthalpies and free energies suggest that these pathways are
not energetically favored. This is evident from the precursor
ion spectra of the ion at m/z 68 (Figure 7). The most facile
dissociation of [M - H2 + Ag]+ is apparently the one in which
Ag+ and the neutral [M - H2 - Ag] species are formed (Figure
3). Two isomeric structures, 8 and 9, are postulated in Scheme
1. As before, the reaction enthalpy and free energy for the
Dissociation of the Ag+-Proline Complex
J. Phys. Chem. B, Vol. 105, No. 49, 2001 12407
Figure 9. Relative free energies (in parentheses, kcal mol-1) at 298 K of Ag+-proline and its dissociation products as calculated at B3LYP/DZVP.
All Structures are at minima. Italicized numbers are m/z values, bold numbers are structure numbers from Schemes 1 and 2.
dissociation of ions 5 to Ag+ and neutral 9 and those for the
equivalent dissociation of ion 6 to Ag+ and neutral 8 are similar.
Figure 2 shows a minor fragmentation product of 107Ag+proline (Figure 2a) and 109Ag+-proline (Figure 2b) at m/z 70,
which apparently shifts to m/z 71 in the fragmentation of 109Ag+-d2-proline (Figure 2c), thus indicating that this ion contains
one H/D-exchangeable hydrogen atom. The proposed structure
for this ion, 10, is shown in Scheme 1; it is formed from Ag+proline by loss of AgH and CO2. Ion 7 contains an imino
hydrogen which is replaced by deuterium, in accordance with
the experimental results in Figure 2. The reaction enthalpy and
free energy for the dissociation of Ag+-proline to ion 10, via
the loss of AgH and CO2, are 35.3 and 14.0 kcal mol-1,
respectively. Dehydrogenation of ion 10 to form ion 7 requires
an enthalpy change of 56.9 kcal mol-1 and a free energy change
of 48.2 kcal mol-1. Alternatively, ion 10 may dehydrogenate
to form ion 11 with, however, much larger enthalpy and free
energy changes (93.0 and 83.2 kcal mol-1).
Scheme 2 addresses the ion chemistry of [M - AgH]+, which
is the principal dissociation product of Ag+-proline (Figure 2).
Formation of [M - AgH]+ is postulated to proceed via two
pathways: path 5 that has a reaction enthalpy and free energy
of 54.8 and 44.0 kcal mol-1 and produces ion 12 and AgH,
and path 6 that has a comparable reaction enthalpy and free
energy of 54.7 and 44.1 kcal mol-1 and produces ion 13 and
AgH. As a consequence, isomers 12 and 13 are almost
equivalent in free energy. Ions 12 and 13 both retain two H/Dexchangeable hydrogen atoms, in accordance with a shift from
m/z 114, products from Ag+-proline (Figure 2b) to m/z 116,
the analogous products from Ag+-d2-proline (Figure 2c). Previously, we have examined the potential energy surface for loss
of AgH from CH3CH2NH2Ag+.33 The mechanism involves two
intermediates, the first in which Ag+ is attached to one of the
hydrogen atoms of the R CH2 group and the second, higher
energy species, in which AgH solvates CH3CHdNH2+. The
overall free energy for this fragmentation pathway is 40.0 kcal
mol-1 i.e., there are no high barriers in this process. Loss of
AgH from argentinated proline has a slightly higher free energy
(44.1 kcal mol-1) and this difference can be attributed to the
breaking of the Ag‚‚‚O interaction. As shown in Scheme 2 for
isomers 12 and 13, subsequent rearrangement followed by the
loss of H2O or D2O produces acylium ions 14 and 15, the
proposed ion structures for m/z 96 observed in Figure 2.
This ion lineage is supported by the data in Figure 5. The
dissociation enthalpy and free energy from ion 12 to ion 14
and water are 60.9 and 49.2 kcal mol-1, respectively. These
are to be compared with a dissociation enthalpy and a free
energy of 58.5 and 46.6 kcal mol-1 for dissociation of ion 13
to ion 15 plus water. The acylium ion 15 is lower in free energy
than its isomer 14 by 2.7 kcal mol-1. Subsequent loss of CO
from the acylium ions results in ions 7 and 11, both of which
have previously been discussed in Scheme 1. There ion 7 is
formed by elimination of AgH and CO2 from 5 and 6, both
isomers of [M - H2 + Ag]+. Here in Scheme 2, dissociation
of ion 15 to ion 7 and CO has an enthalpy and free energy
change of only 6.4 and -4.1 kcal mol-1, respectively. In
comparison, the equivalent dissociation of ion 14 to ion 11 and
CO, however, has a much larger enthalpy and free energy
change of 39.7 and 28.2 kcal mol-1, an effect attributed to high
strain energy in structure 11 resulting from a C≡N bond
constrained in a five-membered ring. This feature makes ion
11 35.0 kcal mol-1 higher in free energy than ion 7. Scheme 2
also shows two examined but subsequently rejected pathways,
12408 J. Phys. Chem. B, Vol. 105, No. 49, 2001
Shoeib et al.
Figure 10. Relative free energies (in parentheses, kcal mol-1) at 298 K for species involved in the loss of H2 and AgH from Ag+-proline. Italicized
numbers are m/z values, bold numbers are structure numbers from Schemes 1 and 2.
for the production of ions 16 and 17, both having a m/z value
identical to that of ion 10. Both of these pathways are easily
rejected as both 16 and 17 contain two exchangeable hydrogen
atoms, in disagreement with the experimental evidence presented
in Figure 2, which clearly shows the presence of only one
H/D-exchangeable hydrogen atom (compare Figure 2b and
Figure 2c).
To determine a branching ratio for paths 5 to 6, we performed
experiments on a selectively labeled proline where the C-H
hydrogen shown with an asterisk (see Scheme 2) is selectively
replaced by a deuterium. Figure 8 shows the collision-induced
dissociation of the Ag+ complex of this selectively labeled
proline. A comparison with Figure 2 reveals that the deuterium
is retained in every ion in Figure 8, thereby providing
incontrovertible evidence that only path 6 is operational in
Scheme 2. Furthermore, observation of the [M* - H2 + Ag]+
ions at m/z 221 and 223, and the absence of the [M* - HD +
Ag]+ at m/z 222 and 224, indicates 100% retention of the
deuterium atom; these results establish that pathways 1 and 3
(as opposed to pathways 2 and 4) are operational in Scheme 1.
The loss of AgH or AgD and CO2 from 5 (see Scheme 1) is
possible. Isomer 5 is the only viable [M - H2 + Ag]+ isomer
that can lead to ion 7. Finally, direct loss of AgH or AgD and
CO2 from ion 2 remains viable as it allows for the retention of
the nonexchangeable deuterium atom in 10; this is supported
by observation of the ion at m/z 71 in Figure 8, a shift of 1 m/z
unit from the equivalent ion at m/z 70 in Figure 2a and 2b. The
subsequent loss of H2 from 10 must produce only 7, which
retains the nonexchangeable deuterium atom, and not 11, which
does not. This is clear from the absence of m/z 68 in Figure 8
and is in agreement with the significantly higher free energy of
11 relative to 7.
Figure 9 shows the structures of the ions observed as
calculated by B3LYP/DZVP. This Figure also provides relative
free energies of the Ag+-proline complex and its fragmentation
products. Only the ions that have viable formation pathways as
discussed in Schemes 1 and 2 are presented. It is of note that
the free energy sum of the acylium ion and its fragmentation
partners AgH and H2O is the highest, in accordance with
Scheme 2.
Figure 10 shows the relative free energies for loss of H2 or
AgH from 2 to produce 5 and 13 via pathways 3 and 6 of
Schemes 1 and 2, respectively. Collisional activation of 2 leads
to TS1 where a proton is migrating away from the secondary
carbon alpha to the amine group and toward the silver. The
latter has now fully dissociated from the nitrogen and is forming
what is, in effect, an ion-molecule complex (MIN1). In MIN1
the dipole of the neutral AgH molecule is aligned such that the
δ+ on the silver solvates the δ- on the oxygen and the δ- on
the AgH hydrogen solvates the δ+ on the NH hydrogen. MIN1
is structurally very similar to TS1, and it is thus not surprising
that it is only 2.6 kcal mol-1 lower in free energy. The
dissociation of MIN1 into AgH and 13 requires only 9.7 kcal
mol-1. From MIN1 the loss of H2 and the production of 5
proceeds via TS2, a structure in which both the AgH and NH
bonds are being broken, and a new H-H bond is being formed.
The free energy of this species is 6.2 kcal mol-1 above TS1,
and only 0.9 kcal mol-1 below that of the separated species
AgH and 13. This is in agreement with the experimental
observation (Figure 3) that ion 5 (at m/z 220 and produced by
the loss of H2) is more abundant than 13 (at m/z 114 and
produced by the loss of AgH) at very low collision energies
(ECM ) 0.2 to 1.2 eV). Maximum abundance of 5 is achieved
Dissociation of the Ag+-Proline Complex
at about ECM ) 2.0 eV; by comparison 13 reaches its maximum
abundance at about ECM ) 2.7 eV.
Acknowledgment. We are grateful to Houssain El Aribi and
Steve Quan for technical assistance. The authors thank the
Natural Sciences and Engineering Research Council of Canada,
MDS SCIEX, the Canadian Foundation for Innovation and the
Ontario Innovation Trust for financial support. T.S. acknowledges financial support in the form of an Ontario Graduate
Scholarship in Science and Technology.
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