Article
Classical Dynamics Simulations of Dissociation of Protonated Tryptophan in the Gas Phase Yogeshwaran Krishnan, Nishant Sharma, Upakarasamy Lourderaj, and Manikandan Paranjothy J. Phys. Chem. A, Just Accepted Manuscript • Publication Date (Web): 24 May 2017 Downloaded from http://pubs.acs.org on May 25, 2017
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Physical Chemistry A is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
Classical Dynamics Simulations of Dissociation of Protonated Tryptophan in the Gas Phase Yogeshwaran Krishnan,† Nishant Sharma,‡ Upakarasamy Lourderaj,‡ and Manikandan Paranjothy∗,† †Department of Chemistry, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India ‡School of Chemical Sciences, National Institute of Science Education and Research, Bhubhaneshwar, Orissa, India. E-mail:
[email protected] Phone: +91 291 244 9082. Fax: +91 291 251 6823
1
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Abstract Gas phase decomposition of protonated amino acids are of great interest due to their role in understanding protein and peptide chemistry. Several experimental and theoretical studies have been reported in the literature on this subject. In the present work, decomposition of the aromatic amino acid protonated tryptophan was studied by on-the-fly classical chemical dynamics simulations using density functional theory. Mass spectrometry and electronic structure theory studies have shown multiple dissociation pathways for this biologically relevant molecule. Unlike aliphatic amino acids, protonated tryptophan dissociates via NH3 elimination rather than the usual iminium ion formation by combined removal of H2 O and CO molecules. Also, a major fragmentation pathway in the present work involves Cα -Cβ bond fission. Results of the chemical dynamics simulations reported here are in overall agreement with experiments and detailed atomic level mechanisms are presented.
Introduction Unimolecular dissociation of protonated amino acids (AAs) has gained considerable attention as they serve as models to study the fragmentation pattern of protonated peptides. Numerous experimental 1–21 and theoretical 22–29 studies have been reported on the fragmentation of AAs spanning over a range of systems from simpler AAs such as glycine 22,23 to as large as tryptophan. 30–32 In the gas phase, aliphatic AAs decompose to form primarily iminium ion 22 with the combined removal of H2 O and CO while for aromatic AAs, NH3 elimination is also a dominant dissociation pathway in addition to several other minor pathways. 6,11,20,21,33 For example, in their mass spectrometry study, Aribi et al., 33 have observed NH3 elimination to be the dominant pathway for phenylalanine, tyrosine, and tryptophan with the exception of histidine. Of particular interest is tryptophan due to its important role in the synthesis of human protein. Fragmentation chemistry of protonated tryptophan (TrpH+ ) has been studied by several spectroscopic techniques, 6,31,34,35 mass spectrometry 2
ACS Paragon Plus Environment
Page 2 of 28
Page 3 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
techniques, 9,36–41 electro-spray ionization followed by ion-trap, 8,11,42 and ab initio electronic structure theory. 36,37,43 Protonation for gas phase neutral tryptophan molecule occurs at the most basic site the amino group rather than the nitrogen atom on the indole side chain. 37,44 It was found 37 that the indole nitrogen protonated isomer is 22.8 kcal/mol higher in energy than the amino protonated isomer at B3LYP/6-31G* level of theory. For NH3 elimination from TrpH+ , several mechanisms involving nucleophilic attack by different sites of the indole ring on the α carbon atom have been proposed and are shown in Figure 1. These include the attack on α carbon by (i) C2 atom leading to the formation of the stable seven membered ring compound A in Figure 1 (proposed by Prokai et al., 45 based on AM1 semi-empirical calculations), (ii) C3 atom to form the spirocyclopropane derivative B (proposed by Lioe et al., 37 based on quadrupole ion trap experiments and electronic structure calculations and further observed by Mino et al., 6 in their infrared multiple-photon dissociation spectra), and (iii) C4 atom preceded by a series of 1,2-hydride shifts leading to the formation of compound C (deuterium labeling and triple quadrupole mass spectrometry experiments by Rogalewicz et al. 10 ) Relative energies of these isomeric A, B, and C species were found to be +10.1, 0.0, +19.5 kcal/mol at B3LYP/6-31G* level of theory 37 with the C3 attack product (B) being the lowest in energy. Also, it was found that H/D scrambling occurred in the TrpH+ molecule prior to NH3 elimination in agreement with the mobile proton model proposed earlier. 46,47 In the present article, we report Born-Oppenheimer ab initio classical chemical dynamics simulations of dissociation of TrpH+ in the gas phase under collision induced dissociation 48 (CID) conditions. Several classical trajectories with suitable initial conditions were propagated on the B3LYP/6-31G* potential energy surface using the direct dynamics methodology. 49,50 Direct dynamics studies on dissociation chemistry of aliphatic amino acids and smaller peptides containing upto eight amino acid units have been reported in the literature. 24–26,51–54 Such studies were performed at semi-empirical level of electronic structure theory. Hase and
3
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
co-workers used analytic potentials and AM1 semi-empirical theory 26 to model collision and surface induced dissociation of protonated glycine and in a later work they used QM+MM methodology utilizing MP2/6-31G* theory 24 to study the surface induced dissociation of protonated glycine. Also, at various levels of electronic structure theory and model analytic potentials they have reported 55–59 detailed dynamics studies on smaller peptides. The results of such studies were in agreement with experiments and provided an atomic level picture of the dissociation process and attributes such as product branching ratios and energy distributions determined. To the best of our knowledge, such dynamics studies on aromatic amino acids, in particular TrpH+ , have not been reported in the literature. In the present work, we are interested in the gas phase dissociation chemistry of TrpH+ molecule in the ground state to model CID experiments. Such experiments can be performed under a range of conditions 60 and in the present work the simulations were performed to model high energy single collision conditions. The next section describes the computational methodology followed by results and discussion. The last section summarizes and concludes the article. Also, some relevant information such as trajectory energy conservation, etc., are presented in supplementary information (SI).
Computational Methodology Electronic structure calculations for different dissociation pathways of TrpH+ have been reported earlier at B3LYP/6-31G* level of theory. 37 In the present work, atomic level mechanisms of the dissociation of TrpH+ were investigated by direct dynamics 49,50 simulations at B3LYP/6-31G* level of theory. For trajectory initial conditions, normal mode vibrational energies and thermal rotational energies for the reactant TrpH+ molecule were chosen from a 300 K Boltzmann distribution. 61 An Ar atom was made to collide with TrpH+ at an impact parameter 62 of 0.0 Å with a relative collision energy of 300.0 kcal/mol (13 eV) to model CID experiments. 48 For these initial conditions the average total energy in the trajectories was
4
ACS Paragon Plus Environment
Page 4 of 28
Page 5 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
TrpH
+
−NH3 C2
C3
A
C4
B
C
Figure 1: Protonated tryptophan (TrpH+ ) molecule showing the atom labeling used for discussion purposes throughout the paper. Elimination of NH3 has been proposed to occur via three different pathways involving nucleophilic attack by C2, C3, or C4 atom on the α carbon atom. These pathways lead to formation of three different products A, B, and C corresponding to C2, C3, and C4 attack, respectively.
455.6 kcal/mol (19.8 eV). TrpH+ molecule was oriented randomly for different trajectories and the initial separation between Ar and the center-of-mass of TrpH+ was kept at 10.0 Å. The initial conditions were propagated by a 6th order symplectic integrator 63,64 to a total integration time of 1 ps with an integration step-size of 0.2 fs or until the dissociation reaction products were sufficiently separated (typically 8.0 - 10.0 Å). The simulations were performed using the general chemical dynamics program VENUS 65,66 interfaced 67 with the electronic structure theory package NWChem. 68 Default convergence criteria for the electronic structure calculations as available in the NWChem program were used. On a DELL PRECISION 16 Core workstation, it took approximately 25 days to integrate one trajectory for 1 ps.
Results and Discussion Here, we discuss results of our chemical dynamics simulations performed for the collisionally activated TrpH+ molecule at B3LYP/6-31G* level of electronic structure theory. A total of 5
ACS Paragon Plus Environment
The Journal of Physical Chemistry
Path 3
G
H
−NH3 −NH3
Path 4
−NH3
Path 1
Path 2
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 6 of 28
D
+
B
E
F
Figure 2: Various pathways observed in the TrpH+ collision induced dissociation. A total of 70 classical trajectories were generated on-the-fly at the B3LYP/6-31G* level of theory. Among these trajectories, 44 dissociated via one of the pathways shown, 19 underwent no reaction and 7 showed intramolecular proton transfer.
6
ACS Paragon Plus Environment
Page 7 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
70 classical trajectories were generated for the Ar + TrpH+ collision at a collision energy of 300.0 kcal/mol (13 eV). Following the collision, 51 out of 70 trajectories either dissociated to form different reaction products or underwent intramolecular proton transfer process and did not dissociate. Rest of the trajectories (19 out of 70) neither dissociated nor underwent proton transfer during the entire integration period of 1 ps. The trajectories were animated to visualize the dissociation channels. Summary of the observed events are presented in Figure 2 and in Table 1. For all the trajectories total energy was conserved within Etotal ±0.2 kcal/mol. Total energy as a function of integration time for a few trajectories is presented in SI. We have also computed the energy transfer to the TrpH+ molecule during the collisions. Distributions of the energy transferred for all the collisions and for different pathways are shown in Figure 3. The average energy deposited in the TrpH+ molecule, over all the collisions, was 185.6 ± 30.7 kcal/mol.
7
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 8 of 28
Table 1: Various Trajectory Events Following Collision Induced Dissociation of TrpH+ Fraction†
Pathway Path 1
13/70
Path 2
25/70
Path 3
5/70
Path 4
1/70
Proton transfer‡
7/70
No Reaction↑
19/70
†
A total of 70 classical trajectories were generated and this column provides the fraction of trajectories dissociated via the corresponding pathway.
‡
Trajectories that showed intramolecular proton transfer but did not dissociate.
↑
Trajectories that neither dissociated nor underwent proton transfer during the integration time of 1 ps.
NH3 Elimination NH3 elimination from gas phase TrpH+ (i.e., the m/z = 188 channel), observed in the mass spectrometry experiments has been proposed to occur via nucleophilic attack by either C2, C3, or C4 atom on the α carbon atom of the amino acid. In our direct dynamics simulations 13 out of 70 trajectories showed NH3 elimination from collisionally activated TrpH+ molecule through nucleophilic attack by the side-chain indole and in all the 13 trajectories, attack by C3 carbon atom of the side-chain on the α carbon atom was observed (path 1, Figure 2). We did not observe any trajectory showing nucleophilic attack either by C2 or 8
ACS Paragon Plus Environment
Page 9 of 28
(a)
All
(b)
Path 1
(c)
Path 2
(d)
No Reaction
0.9 0.6 0.3 0 0.9 0.6 0.3 0 100
150
200
250
100
150
200
250
E (kcal/mol)
Figure 3: Distribution of energy transferred to the TrpH+ molecule in collisions for (a) all the trajectories, those trajectories showing (b) path 1, (c) path 2, and (d) no reaction. Ranges of the x- and y- axes are same in all the four plots.
30
E (kcal/mol)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
(24.1)
(23.3)
10
S-TrpH
IA
+
(12.1)
(10.9)
0
B + NH3
TS
20
TrpH
+
(0.0)
Figure 4: Potential energy profile for the NH3 elimination pathway through nucleophilic attack by C3 atom on the α carbon of TrpH+ . The energies are relative to the lowest energy conformer of TrpH+ and computed at the B3LYP/6-31G* level of theory.
9
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
C4 atom. This result is in consistent with the earlier investigations by Lioe et al., 37 and Mino et al. 6 Electronic structure calculations at B3LYP/6-31G* by the former group showed that the spirocyclopropane derivative B in Figure 1 corresponds to the lowest energy isomer among the possible A, B, and C products. 37 Further, Mino et al., 6 observed spectral bands corresponding only to species B in their infrared multiple-photon dissociation study of TrpH+ . The m/z = 188 fragmentation channel has also been observed in fast atom bombardment mass spectrometry 20 and MALDI TOF/TOF tandem mass spectrometry. 21 The reaction profile for this pathway is shown in Figure 4. Stationary points were computed at the B3LYP/6-31G* level of theory and also have been reported in the earlier work. 37 Rotation of the Cα -Cβ bond leads to the higher energy conformer S−TrpH+ which goes through the NH3 elimination transition state (TS). This TS is 23.3 kcal/mol higher in energy as compared to the lowest energy conformer TrpH+ and goes through the B...NH3 intermediate (IA) before dissociating as the final products B + NH3 . (a)
(b) 45 fs
175 fs
393 fs
952 fs
567 fs
477 fs
1
Figure 5: (a) Snapshots of a typical trajectory1showing NH3 elimination through C3 nucleophilic attack. Close to 380 fs, the C3 atom attacks the α carbon atom of the amino acid with Cα -N cleavage beginning simultaneously. (b) Relevant bond distances for the same trajectory as a function of time.
The average energy transfer to the TrpH+ molecule in trajectories showing this pathway was 194.6 ± 29.3 kcal/mol and the energy distributions are shown in Figure 3(b). Though 10
ACS Paragon Plus Environment
Page 10 of 28
Page 11 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
intramolecular proton transfer was observed in our simulations (see below), the trajectories under discussion in this section did not show any proton transfer prior to dissociation. The H/D scrambling reported to occur prior to NH3 elimination from TrpH+ , leading to the removal of ND3 , ND2 H, and NH2 D, observed by Lioe et al., 37 and Rogalewicz et al., 10 in mass spectrometry experiments were not seen in our simulations. For a typical trajectory showing NH3 elimination through C3 nucleophilic attack snapshots of the trajectory animation at various times are shown in Figure 5(a). At around 380 fs the C3 atom attacks the α carbon atom with simultaneous cleavage of the Cα -N bond. Relevant bond distances are shown in Figure 5(b) and this clearly establishes the operating SN 2 mechanism. 69 The spirocyclopropane derivative B resulting from the nucleophilic attack did not dissociate further in our simulations. Coincidence experiments by Lepére et al., 11 have shown that NH3 elimination from TrpH+ is a fast process (t < 100 ns) and further dissociation of the resulting product B that leads to CO2 loss or C2 H2 O are slow processes (t > 1 µs). As our simulations were performed only for a duration of 1 ps, we did not observe further dissociation of B. To investigate this further, we propagated one NH3 elimination trajectory to 5 ps total integration time and we did not observe dissociation of B. The concomitant loss of H2 O + CO leading to the formation of iminium ion, which is the common dissociation channel 22 for protonated aliphatic AAs and aromatic AAs such as phenyl alanine and tyrosine was not seen in our simulations of TrpH+ decomposition. This is consistent with the earlier CID studies 33,37 which showed that NH3 elimination to be the most dominant pathway from TrpH+ . As reported earlier 37 and verified by us, the transition state barrier heights for NH3 elimination and the combined H2 O + CO elimination are +23.3 and +50.0 kcal/mol (measured from the lowest energy TrpH+ conformer), respectively, at B3LYP/6-31G* level of theory. Hence, the former pathway is energetically favored and also dominant in our simulations.
11
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 12 of 28
(a)
(b) 64 fs
114 fs
138 fs
(c)
377 fs
338 fs
330 fs
1
1
Figure 6: (a) Snapshots of a typical trajectory 1 showing Cα -Cβ bond cleavage. This is a direct dissociation pathway and dissociation for this trajectory happens around 130 fs. Also, intramolecular proton transfer from amino group to the carbonyl oxygen is visible at 338 fs. (b) Potential energy profile for the intramolecular proton transfer between the neutral product E and F resulting from the binary cleavage. (c) Average time at which the corresponding Cα -Cβ distance is reached in the trajectories showing binary fragmentation.
12
ACS Paragon Plus Environment
Page 13 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
Cleavage of the Cα -Cβ Bond Another major fraction of trajectories (25 out of 70) showed cleavage of the Cα -Cβ bond leading to the dissociation products D and the neutral species E (path 2, Table 1). This pathway is a two-body direct dissociation 11 or binary fragmentation 70 (path 2, Figure 2) and the cleavage happens for all the trajectories in less than 500 fs. The collisional energy transfer to the TrpH+ molecule in trajectories showing this pathway was higher (with an average of 201.6 ± 20.1 kcal/mol) and the energy distribution is shown in Figure 3(c). The dissociation products are D, the resonance stabilized, 71 charged aromatic chromophore (m/z = 130) and the neutral fragment is E with m/z = 75. The aromatic chromophore D has been observed as a dominant dissociation product from TrpH+ in several experiments. Kulik et al., 20 have reported 33 % formation of species with m/z = 130 (and 28 % for m/z = 188 which corresponds to NH3 elimination above) from TrpH+ dissociation in their fast atom bombardment mass spectrometry experiments. A relative abundance of greater than 75 % has been reported for m/z = 130 fragment in a collision induced dissociation study by MALDI TOF/TOF tandem mass spectrometry. 21 Further, high collision energy chemical ionization experiments 71,72 have also shown this species as a dominant fragmentation component in mass spectra. The structure of the two species D and E resulting from the Cα -Cβ fission were confirmed by electronic structure calculations at B3LYP/6-31G* level of theory. In our simulations the Cα -Cβ cleavage occurred fast much before our total integration time of 1 ps. Figure 6(c) shows the average (over trajectories) time at which the corresponding Cα -Cβ distance is reached. Out of the 25 trajectories that underwent Cα -Cβ bond cleavage 14 trajectories showed intramolecular proton transfer in the neutral species E leading to the formation of F (Figure 2). The species E is related to F by an intramolecular proton transfer from the amine group to the carbonyl oxygen of the carboxylic moiety with a barrier height of 1.35 kcal/mol. Further, F is more stable by 1.84 kcal/mol with respect to E. The potential energy profile for this process is shown in Figure 6(b). If the trajectories were to be integrated for a long 13
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
time, it is expected that all the trajectories undergoing Cα -Cβ binary cleavage might result in species F as the final neutral product. Snapshots of a trajectory showing Cα -Cβ bond cleavage is shown in Figure 6(a). At around 130 fs dissociation happens for this trajectory. The intramolecular proton transfer from the amine group to the carbonyl oxygen is also visible at 338 fs. Further, the Cα -Cβ bond cleavage pathway appears to be barrierless. Search for a transition state for this pathway using different configurations at the B3LYP/6-31G* level did not succeed. To validate this, a potential energy scan along the Cα -Cβ bond distance with the rest of the coordinates of the entire system held fixed was performed. The Cα -Cβ distance was varied from 2.6 Å to 6.0 Å with a step size of 0.05 Å and single point energies were computed. The results are summarized in Figure 7 and it is clear that there are no signatures for the existence of a barrier for the Cα -Cβ cleavage.
Figure 7: Potential energy scan of the Cα -Cβ bond distance resulting in the formation of species D and E, performed at the B3LYP/6-31G* level of theory. During the scan, rest of the coordinates of the system were held fixed.
Minor Pathways Apart from the two major pathways discussed above, a few trajectories showed minor dissociation channels that are briefly described here. Five trajectories decomposed via pathway 3 as shown in Figure 2. This pathway is also an NH3 elimination pathway which involves direct 14
ACS Paragon Plus Environment
Page 14 of 28
Page 15 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
removal of NH3 from TrpH+ upon collision followed by an immediate proton transfer from the β carbon (methylenic −CH2 group, see Figure 2 for description) to the α carbon atom forming the positively charged species G. In an earlier work, Aribi et al., 33 has invoked a structure similar to G in a scheme they proposed for the decomposition of TrpH+ which was further proposed to dissociate to form various radical products. Since our simulations were carried for a total integration time of 1 ps only, further dissociation of G was not observed. Snapshots of a typical trajectory showing path 3 are given in SI. One trajectory showed yet another NH3 elimination pathway that involves NH3 elimination followed by intramolecular proton transfers from the −OH moiety of the carboxylic group to the C2 carbon atom of the indole sidechain and another transfer from methylenic −CH2 group to the carbonyl oxygen of the acid group (path 4, Figure 2). Among the trajectories showing path 2, one trajectory underwent Cα -Cβ cleavage to form D and the neutral species E from which H2 O was eliminated. Proton transfer happened from the amino group to the −OH of the acid moiety, followed by cleavage of C−O bond resulting in H2 O and H2 NCHCO. We did not investigate these minor pathways any further.
Intramolecular Proton Transfer In our direct dynamics simulations seven trajectories showed intramolecular proton transfer following collision with the Ar atom without any further dissociation. The proton transfers happened in 2, 4, and 1 trajectories from the protonated amine group to the C2, C3, and C4 atoms of the indole sidechain, respectively. The barrier heights at the B3LYP/6-31G* level of theory for proton transfer to the C2, C3, and C4 positions are 14.8, 15.2, and 20.4 kcal/mol, respectively. Corresponding energies and geometries involved in the proton transfer processes are given in Figure 8. Transfer to C4 position involves a seven membered transition state and the barrier height is higher. For the C2 and C3 positions, the barrier heights are similar and involve six and five membered transition states. For the NH3 elimination pathway discussed above, mass spectrometry experiments have provided evidence 10,37 for 15
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 16 of 28
proton transfer occurring before the nucleophilic substitution. In our simulations we did not observe proton transfer in any of the trajectories that showed NH3 elimination through nucleophilic substitution probably due to the limited number of trajectories. TS #
C2 (14.8)
(8.4)
(15.2)
(10.7)
TS # C3
(0.0)
TrpH +
TS #
C4
(20.3)
(16.4)
Figure 8: Energies and geometries involved in the intramolecular proton transfer processes in TrpH+ molecule. The numbers in parentheses are the energies (in kcal/mol) of the corresponding species relative to that of TrpH+ molecule.
Summary and Conclusion Classical chemical dynamics simulations of gas phase dissociation of protonated tryptophan under CID conditions are reported here. Trajectory results are in agreement with experimental observations and atomic level mechanisms presented. Out of the 70 trajectories integrated, 44 trajectories dissociated within our simulation time of 1 ps. Two major dissociation channels were observed along with a few minor pathways. The first major pathway observed was NH3 elimination from TrpH+ . This is consistent with the earlier studies 22,33,37 that aromatic amino acids show NH3 elimination preferentially and aliphatic amino acids 16
ACS Paragon Plus Environment
Page 17 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
decompose to form iminium ion with the removal of H2 O and CO. Visualization of the trajectories indicated that the NH3 elimination mechanism from TrpH+ involves nucleophilic attack 6,37 by the C3 atom of the indole side-chain on the α carbon atom leading to the formation of the spirocyclopropane derivative B (path 1). Apart form these trajectories, six more showed NH3 elimination from TrpH+ but the mechanisms and reaction products were different as compared to the nucleophilic substitution pathway. The second major pathway observed in the simulations was the binary fragmentation of the Cα -Cβ bond, forming the charged conjugated species D and the neutral E which undergoes intramolecular proton transfer with ease to form F. Further, a few trajectories showed intramolecular proton transfer without any major dissociation of the TrpH+ molecule. Dynamics simulations reported here are pertinent to CID processes rather than optical excitation experiments. Interesting optical spectroscopic studies have been reported on the excited state dynamics of TrpH+ . For example, neutral H atom loss from TrpH+ following ultraviolet excitation is specific to optical processes and not observed in CID experiments. 39 Several other photofragmentation studies from excited TrpH+ have been reported 11,42 and modeling such experiments requires careful excited state dynamics calculations. It is also important to perform dynamics simulations similar to the one reported here for smaller peptides involving a few amino acid units. Though a few such studies at semi-empirical level of theory exists, 24–26,51–54 an exhaustive ab initio dynamics studies on peptides are not available. In our simulations, several trajectories (19 out of 70) did not show bond cleavage during the entire simulation time. Average collision energy deposited in the TrpH+ molecule in these non-reactive trajectories was 157.6 kcal/mol which is lower than that for the reactive trajectories (Figure 3). Also, for most of these unreactive trajectories, collision of Ar happens at the side chain indole ring. This may be an indication of restricted energy flow from the indole ring to the reactive sites of TrpH+ . Despite the fact that density of states for a large molecule like TrpH+ will be enormous, our simulations point to non-statistical energy flow. 73 With the present ab initio direct dynamics methodology and fast computer algorithms,
17
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
studying detailed intramolecular vibrational energy redistribution (IVR) dynamics and mode specific behavior in such a big molecule will be an interesting future work.
Supporting Information Available Trajectory snapshots for a path 3 trajectory, total energy as a function of time for a few trajectories, and complete list of authors for references 11, 40, 42, 65, and 68. This material is available free of charge via the Internet at http://pubs.acs.org/.
Acknowledgement Funding from Department of Science and Technology, India, through grants SB/FT/CS053/2013 and SR/S1/PC/0060/2010 is acknowledged. Part of the simulations were carried out in C-DAC (NPSF) Computational facility, Pune, India and High Performance Computing facility, National Institute of Science Education and Research, Bhubhaneshwar, India.
References (1) Junk, G.; Svec, H. The Mass Spectra of the α-Amino Acids. J. Am. Chem. Soc. 1963, 85, 839 - 845. (2) Dookeran, N. N.; Yalcin, T.; Harrison, A. G. Fragmentation Reactions of Protonated α-Amino Acids. J. Mass Spectrom. 1996, 31, 500 - 508. (3) Zhao, J.; Shoeib, T.; Siu, K. W. M.; Hopkinson, A. C. The Fragmentation of Protonated Tyrosine and Iodotyrosines: The Effect of Substituents on the Losses of NH3 and of H2 O and CO. Int. J. Mass Spectrom. 2006, 255, 265 - 278. (4) Heaton, A. L.; Armentrout, P. B. Thermodynamics and Mechanism of Protonated Asparagine Decomposition. J. Am. Soc. Mass Spectrom. 2009, 20, 852 - 866. 18
ACS Paragon Plus Environment
Page 18 of 28
Page 19 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
(5) Beranová, S.; Cai, J.; Wesdemiotis, C. Unimolecular Chemistry of Protonated Glycine and Its Neutralized Form in the Gas Phase. J. Am. Chem. Soc. 1995, 117, 9492 - 9501. (6) Mino, W. K. Jr.; Gulyuz, K.; Wang, D.; Stedwell, C. N.; Polfer, N. C. Gas-Phase Structure and Dissociation Chemistry of Protonated Tryptophan Elucidated by Infrared Multiple Photon Dissociation Spectroscopy. J. Phys. Chem. Lett. 2011, 2, 299 - 304. (7) Lioe, H.; O’Hair, R. A. J. Comparison of Collision-induced Dissociation and Electroninduced Dissociation of Singly Protonated Aromatic Amino Acids, Cystine and Related Simple Peptides Using a Hybrid Linear Ion Trap- FT-ICR Mass Spectrometer. Anal. Bioanal. Chem. 2007, 389, 1429 - 1437. (8) Talbot, F. O.; Tabarin, T.; Antoine, R.; Broyer, M.; Dugourd, P. Photo-dissociation Spectroscopy of Trapped Protonated Tryptophan. J. Chem. Phys. 2005, 122, 074310. (9) Kang, H.; Jouvet, C.; Dedonder-Lardeux, C.; Martrenchard, S.; Grégoire, G.; Desfrançois, C.; Schermann, J. -P.; Barat, M.; Fayeton, J. A. Ultrafast Deactivation Mechanisms of Protonated Aromatic Amino Acids Following UV Excitation. Phys. Chem. Chem. Phys. 2005, 7, 394 - 398. (10) Rogalewicz, F.; Hoppilliard, Y.; Ohanessian, G. Fragmentation Mechanisms of α-amino Acids Protonated Under Electrospray Ionization: A Collisional Activation and Ab Initio Theoretical Study. Int. J. Mass Spectrom. 2000, 195/196, 565 - 590. (11) Lepére, V.; Lucas, B.; Barat, M.; Fayeton, J. A.; Picard, V. J.; Jouvet, C.; Çarçabal, P.; Nielsen, I.; Dedonder-Lardeux, C.; Grégoire, G.; et al. Comprehensive Characterization of the Photo-dissociation Pathways of Protonated Tryptophan. J. Chem. Phys. 2007, 127, 134313. (12) Armentrout, P. B.; Heaton, A. L.; Ye, S. J. Thermodynamics and Mechanisms for Decomposition of Protonated Glycine and Its Protonated Dimer. J. Phys. Chem. A 2011, 115, 11144 - 11155. 19
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
(13) O’Hair, R. A. J.; Styles, M. L.; Reid, G. E. Role of the Sulfhydryl Group on the Gas Phase Fragmentation Reactions of Protonated Cysteine and Cysteine Containing Peptides. J. Am. Soc. Mass Spectrom. 1998, 9, 1275 - 1284. (14) O’Hair, R. A. J.; Reid, G. E. Neighboring Group Versus Cis-elimination Mechanisms for Side Chain Loss from Protonated Methionine, Methionine Sulfoxide and Their Peptides. Eur. Mass Spectrom. 1999, 5, 325 - 334. (15) Reid, G. E.; Simpson, R. J.; O’Hair, R. A. J. A Mass Spectrometric and Ab Initio Study of the Pathways for Dehydration of Simple Glycine and Cysteine-Containing Peptide [M+ H]+ Ions. J. Am. Soc. Mass Spectrom. 1998, 9, 945 - 956. (16) O’Hair, R. A. J.; Reid, G. E. Does Side Chain Water Loss from Protonated Threonine Yield N-Protonated Dehydroamino-2-butyric acid?. Rapid Commun. Mass Spectrom. 1998, 12, 999 - 1002. (17) Reid, G. E.; Simpson, R. J.; O’Hair, R. A. J. Probing the Fragmentation Reactions of Protonated Glycine Oligomers via Multistage Mass Spectrometry and Gas Phase Ion Molecule Hydrogen/deuterium Exchange. Int. J. Mass Spectrom. 1999, 190/191, 209 230. (18) Reid, G. E.; Simpson, R. J.; O’Hair, R. A. J. Leaving Group and Gas Phase Neighboring Group Effects in the Side Chain Losses from Protonated Serine and its Derivatives. J. Am. Soc. Mass Spectrom. 2000, 11, 1047 - 1060. (19) Van der Greef, J.; Ten Noever de Brauw, M. C.; Zwinselman, J. J.; Nibbering, N. M. M. A Fast Atom Bombardment Study of Methionine in Combination With Deuterium Labeling. Org. Mass Spectrom. 1982, 17, 274 - 276. (20) Kulik, W.; Heerma, W. A Study of the Positive and Negative Ion Fast Atom Bombardment Mass Spectra of α-Amino Acids. Biomed. Environ. Mass Spectrom. 1988, 15, 419 427. 20
ACS Paragon Plus Environment
Page 20 of 28
Page 21 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
(21) Gogichaeva, N. V.; Williams, T.; Alterman, M. A. MALDI TOF/TOF Tandem Mass Spectrometry as a New Tool for Amino Acid Analysis. J. Am. Soc. Mass Spectrom. 2007, 18, 279 - 284. (22) O’Hair, R. A. J.; Broughton, P. S.; Styles, M. L.; Frink, B. T.; Hadad, C. M. The Fragmentation Pathways of Protonated Glycine: A Computational Study. J. Am. Soc. Mass Spectrom. 2000, 11, 687 - 696. (23) Rogalewicz, F.; Hoppilliard, Y. Low Energy Fragmentation of Protonated Glycine. An Ab Initio Theoretical Study. Int. J. Mass Spectrom. 2000, 199, 235 - 252. (24) Park, K.; Song, K.; Hase, W. L. An Ab Initio Direct Dynamics Simulation of Protonated Glycine Surface-induced Dissociation. Int. J. Mass Spectrom. 2007, 265, 326 - 336. (25) Spezia, R.; Lee, S. B.; Cho, A.; Song, K. Collision-induced Dissociation Mechanisms of Protonated Penta- and Octa-glycine as Revealed by Chemical Dynamics Simulations. Int. J. Mass Spectrom. 2015, 392, 125 - 138. (26) Meroueh, S. O.; Wang, Y.; Hase, W. L. Direct Dynamics Simulations of Collision and Surface-Induced Dissociation of N-Protonated Glycine. Shattering Fragmentation. J. Phys. Chem. A 2002, 106, 9983 - 9992. (27) Simon, S.; Gil, A.; Sodupe, M.; Bertran, J. Structure and Fragmentation of Glycine, Alanine, Serine and Cysteine Radical Cations. A Theoretical Study. J. Mol. Struc. THEOCHEM 2005, 727, 191 - 197. (28) Armentrout, P. B.; Heaton, A. L. Thermodynamics and Mechanisms of Protonated Diglycine Decomposition:A Computational Study. J. Am. Soc. Mass Spectrom. 2012, 23, 621 - 631. (29) Uggerud, E. The Unimolecular Chemistry of Protonated Glycine and the Proton Affinity of Glycine: A Computational Model. Theo. Chem. Acc. 1997, 97, 313 - 316. 21
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
(30) Grégoire, G.; Jouvet, C.; Dedonder, C.; Sobolewski, A. L. Ab initio Study of the Excited-State Deactivation Pathways of Protonated Tryptophan and Tyrosine. J. Am. Chem. Soc. 2007, 129, 6223 - 6231. (31) Boyarkin, O. V.; Mercier, S. R.; Kamariotis, A.; Rizzo, T. R. Electronic Spectroscopy of Cold, Protonated Tryptophan and Tyrosine. J. Am. Chem. Soc. 2006, 128, 2816 2817. (32) Nolting, D.; Marian, C.; Weinkauf, R. Protonation Effect on the Electronic Spectrum of Tryptophan in the Gas Phase. Phys. Chem. Chem. Phys. 2004, 6, 2633 - 2640. (33) Aribi, H. E.; Orlova, G.; Hopkinson, A. C.; Siu. K. W. M. Gas-Phase Fragmentation Reactions of Protonated Aromatic Amino Acids: Concomitant and Consecutive Neutral Eliminations and Radical Cation Formations. J. Phys. Chem. A 2004, 108, 3844 - 3853. (34) Rizzo, T. R.; Park, Y. D.; Peteanu, L. A.; Levy, D. H. The Electronic Spectrum of the Amino Acid Tryptophan in the Gas Phase. J. Chem. Phys. 1986, 84, 2534 - 2541. (35) Grégoire, G.; Lucas, B.; Barat, M.; Fayeton, J. A.; Dedonder-Lardeux, C.; Jouvet, C. UV Photoinduced Dynamics in Protonated Aromatic Amino Acid. Eur. Phys. J. D 2009, 51, 109 - 116. (36) Lioe, H.; O’Hair, R. A. J.; Reid, G. E. A Mass Spectrometric and Molecular Orbital Study of H2 O Loss from Protonated Tryptophan and Oxidized Tryptophan Derivatives. Rapid Commun. Mass Spectrom. 2004, 18, 978 - 988. (37) Lioe, H.; O’Hair, R. A. J.; Reid, G. E. Gas-Phase Reactions of Protonated Tryptophan. J. Am. Soc. Mass Spectrom. 2004, 15, 65 - 76. (38) Kadhane, U.; Andersen, J. U.; Ehlerding, A.; Hvelplund, P.; Kirketerp, M. B. S.; Lykkegaard, M. K.; Nielsen, S. B.; Panja, S.; Wyer, J. A.; Zettergren, H. Photodissociation
22
ACS Paragon Plus Environment
Page 22 of 28
Page 23 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
of Protonated Tryptophan and Alteration of Dissociation Pathways by Complexation with Crown Ether. J. Chem. Phys. 2008, 129, 184304. (39) Kang, H.; Dedonder-Lardeux, C.; Jouvet, C.; Martrenchard, S.; Grégoire, G.; Desfrançois, C.; Schermann, J. -P.; Barat, M.; Fayeton, J. A. Photo-induced Dissociation of Protonated Tryptophan TrpH+ : A Direct Dissociation Channel in the Excited States Controls the Hydrogen Atom Loss. Phys. Chem. Chem. Phys. 2004, 6, 2628 - 2632. (40) Piatkivskyi, A.; Osburn, S.; Jaderberg, K.; Grzetic, J.; Steill, J. D.; Oomens, J.; Zhao, J.; Lau, J. K, C.; Verkerk, U. H.; Hopkinson, A. C.; et al. Structure and Reactivity of the Distonic and Aromatic Radical Cations of Tryptophan. J. Am. Soc. Mass Spectrom. 2013, 24, 513 - 523. (41) Cai, T.; Wang, D.; Xu, X.; Fang, D.; Qi, H.; Jiang, Y. New Evidence for H/D Scrambling of Tryptophan and its Analogues in the Gas Phase. Int. J. Mass Spectrom. 2015, 385, 26 - 31. (42) Lepère, V.; Lucas, B.; Barat, M.; Fayeton, A. J.; Picard, J. Y.; Jouvet, C.; Çarçabal, P.; Nielsen, I.; Dedonder-Lardeux, C.; Grégoire, G.; et al. Characterization of Neutral Fragments Issued from the Photo-dissociation of Protonated Tryptophane. Phys. Chem. Chem. Phys. 2007, 9, 5330 - 5334. (43) Grégoire, G.; Jouvet, C.; Dedonder, C.; Sobolewski, A. L. On the Role of Dissociative πσ ∗ States in the Photochemistry of Protonated Tryptamine and Tryptophan: An Ab Initio Study. Chem. Phys. 2006, 324, 398 - 404. (44) Maksić, Z. B.; Kova˘ccević, B. Towards the Absolute Proton Affinities of 20 α-amino acids. Chem. Phys. Lett. 1999, 307, 497 - 504. (45) Prokai, L.; Prokai-Tatrai, K.; Pop, E.; Bodor, N.; Lango, J.; Roboz, J. Fast Atom Bombardment and Tandem Mass Spectrometry of Quaternary Pyridinium Salt-type Tryptophan Derivatives. Org. Mass Spectrom. 1993, 28, 707 - 715. 23
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
(46) Harrison, A. G.; Yalcin, T. Proton Mobility in Protonated Amino Acids and Peptides. Int. J. Mass Spectrom. Ion Proces. 1997, 165/166, 339 - 347. (47) Csonka, I. P.; Paizs, B.; Lendvay, G.; Suhai, S. Proton Mobility in Protonated Peptides: A Joint Molecular Orbital and RRKM Study. Rapid Commun. Mass Spectrom. 2000, 14, 417 - 431. (48) Papayannopoulos, I. A. The Interpretation of Collision-induced Dissociation Tandem Mass Spectra of Peptides. Mass Spectrom. Rev. 1995, 14, 49 - 73. (49) Sun, L.; Hase, W. L. Born-Oppenheimer Direct Dynamics Classical Trajectory Simulations. Rev. Comput. Chem. 2003, 19, 79 - 146. (50) Paranjothy, M.; Sun, R.; Zhuang, Y.; Hase, W. L. Direct Chemical Dynamics Simulations: Coupling of Classical and Quasiclassical Trajectories with Electronic Structure Theory. WIREs Comput. Mol. Sci. 2013, 3, 296 - 316. (51) Spezia, R.; Martin-Somer, A.; Macaluso, V.; Homayoon, Z.; Pratihar, S.; Hase, W. L. Unimolecular Dissociation of Peptides: Statistical vs. Non-statistical Fragmentation Mechanisms and Time Scales. Faraday Discuss. 2016, 195, 599 - 618. (52) Homayoon, Z.; Pratihar, S.; Dratz, E.; Snider, R.; Spezia, R.; Barnes, G. L.; Macaluso, V.; Martin-Somer, A.; Hase, W. L. Model Simulations of the Thermal Dissociation of the TIK(H+ )2 Tripeptide: Mechanisms and Kinetic Parameters. J. Phys. Chem. A 2016, 120, 8211 - 8227. (53) Ortiz, D.; Martin-Gago, P.; Riera, A.; Song, K.; Salpin, J.; Spezia, R. Gas-Phase Collision Induced Dissociation Mechanisms of Peptides: Theoretical and Experimental Study of N-formylalanylamide Fragmentation. Int. J. Mass Spectrom. 2013, 335, 33 - 44. (54) Spezia, R.; Martens, J.; Oomens, J.; Song, K. Collision-Induced Dissociation Path-
24
ACS Paragon Plus Environment
Page 24 of 28
Page 25 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
ways of Protonated Gly2 NH2 and Gly3 NH2 in the Short Time-scale Limit by Chemical Dynamics and Ion Spectroscopy. Int. J. Mass Spectrom. 2015, 388, 40 - 52. (55) Wang, Y.; Hase, W. L.; Song, K. Direct Dynamics Study of N-Protonated Diglycine Surface-Induced Dissociation.Influence of Collision Energy. J. Am. Soc. Mass Spectrom. 2003, 14, 1402 - 1412. (56) Wang, J.; Meroueh, S. O.; Wang, Y.; Hase, W. L. Efficiency of Energy Transfer in Protonated Diglycine and Dialanine SID Effects of Collision Angle, Peptide Ion Size, and Intramolecular Potential. Int. J. Mass Spectrom. 2003, 230, 57 - 64. (57) Rahaman, A.; Zhou, J. B.; Hase, W. L. Effects of Projectile Orientation and Surface Impact Site on the Efficiency of Projectile Excitation in Surface-induced Dissociation Protonated Diglycine Collisions with Diamond {1 1 1}. Int. J. Mass Spectrom. 2006, 249, 321 - 329. (58) Park, K.; Deb, B.; Song, K.; Hase, W. L. Importance of Shattering Fragmentation in the Surface-Induced Dissociation of Protonated Octaglycine. J. Am. Soc. Mass Spectrom. 2009, 20, 939 - 948. (59) Barnes, G. L.; Young, K.; Yang, L.; Hase, W. L. Fragmentation and Reactivity in Collisions of Protonated Diglycine with Chemically Modified Perfluorinated Alkylthiolateself-assembled Monolayer Surfaces. J. Chem. Phys. 2011, 134, 094106. (60) McLuckey, S. A.; Goeringer, D. E. Slow Heating Methods in Tandem Mass Spectrometry. J. Mass Spectrom. 1997, 32, 461 - 474. (61) Peslherbe, G. H.; Wang, H.; Hase, W. L. Monte Carlo Sampling for Classical Trajectory Simulations. Adv. Chem. Phys. 1999, 105, 171 - 201. (62) Levine, R. D. Molecular Reaction Dynamics, Cambridge University Press, U.K, 2009.
25
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
(63) Schlier, C.; Seiter, A. Symplectic Integration of Classical Trajectories: A Case Study. J. Phys. Chem. A 1998, 102, 9399 - 9404. (64) Schlier, C.; Seiter, A. High-order Symplectic Integration: An Assessment. Comput. Phys. Commun. 2000, 130, 176 - 189. (65) Hase, W. L.; Duchovic, R. J.; Hu, X.; Komornicki, A.; Lim, K. F.; Lu, D.-h.; Peslherbe, G. H.; Swamy, K. N.; Vande Linde, S. R.; Varandas, A.; et al. VENUS. A General Chemical Dynamics Computer Program. Quantum Chemistry Program Exchange (QCPE) Bulletin 1996, 16, 671. (66) Hu, X.; Hase, W. L.; Pirraglia, T. Vectorization of the General Monte Carlo Classical Trajectory Program VENUS. J. Comput. Chem. 1991, 12, 1014 - 1024. (67) Lourderaj, U.; Sun, R.; Kohale, S. C.; Barnes, G. L.; De Jong, W. A.; Windus, T. L.; Hase, W. L. The VENUS/NWChem Software Package. Tight Coupling Between Chemical Dynamics Simulations and Electronic Structure Theory. Comput. Phys. Commun. 2014, 185, 1074 - 1080. (68) Valiev, M.; Bylaska, E. J.; Govind, N.; Kowalski, K.; Straatsma, T. P.; Van Dam, H. J. J.; Wang, D.; Nieplocha, J.; Apra, E.; Windus, T. L.; et al. NWChem: A Comprehensive and Scalable Open-source Solution for Large Scale Molecular Simulations. Comput. Phys. Commun. 2010, 181, 1477 - 1489. (69) McMurry, J. E. Organic Chemistry, 3rd Ed,; Belmont, Wadsworth. 1992. (70) Soorkia, S.; Dehon, C.; Kumar, S. S.; Pérot-Taillandler, M.; Lucas, B.; Jouvet, C.; Barat, M.; Fayeton, J. A. Ion-Induced Dipole Interactions and Fragmentation Times: Cα-Cβ Chromophore Bond Dissociation Channel. J. Phys. Chem. Lett. 2015, 6, 2070 2074.
26
ACS Paragon Plus Environment
Page 26 of 28
Page 27 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
The Journal of Physical Chemistry
(71) Milne, G. W. A.; Axenrod, T.; Fales, H. M. Chemical Ionization Mass Spectrometry of Complex Molecules. IV. Amino Acids. J. Am. Chem. Soc. 1970, 92, 5170 - 5175. (72) Tsang, C. W.; Harrison, A. G. Chemical Ionization of Amino Acids. J. Am. Chem. Soc. 1976, 98, 1301 - 1308. (73) Lourderaj, U.; Hase, W. L. Theoretical and Computational Studies of non-RRKM Unimolecular Dynamics. J. Phys. Chem. A 2009, 113, 2236 - 2253.
27
ACS Paragon Plus Environment
The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Graphical TOC Entry Protonated Tryptophan
+
Collision Induced Dissociation
28
ACS Paragon Plus Environment
Page 28 of 28
