Computational Study of H2S Release in Reactions of Diallyl

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Computational Study of HS Release in Reactions of Diallyl Polysulfides with Thiols You-Ru Cai, and Ching-Han Hu J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.7b03683 • Publication Date (Web): 13 Jun 2017 Downloaded from http://pubs.acs.org on June 17, 2017

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The Journal of Physical Chemistry

Computational Study of H2S Release in Reactions of Diallyl Polysulfides with Thiols

You-Ru Cai, Ching-Han Hu*

Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan

C.-H. Hu, E-mail: [email protected]

1

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Abstract Hydrogen sulfide (H2S) is a gasotransmitter molecule recognized for its role in cell signaling. Garlic-derived polysulfides including diallyl disulfide (DADS) and diallyl trisulfide (DATS) have been shown to release H2S. We investigated the mechanism of the reaction of DADS and DATS with biological thiols, including cysteine (Cys) and glutathione (GSH) using density functional theory. We propose that Cys and GSH react with DADS and DATS in their anionic forms. Thiol anions are much more likely to attack the sulfur atoms of DADS and DATS than the α-carbon of allyl groups. We found that nucleophilic attack of thiol anions on the peripheral sulfur of DATS is kinetically and thermodynamically more favorable than that on the central sulfur atom, resulting in the formation of allyl perthiol anion (ASS–). In the presence of Cys or GSH, H2S is released by proton-shuffle from the thiol to ASS–, followed by another nucleophilic attack by thiol anion on ASSH. Our computed potential energy surfaces revealed that GSH and Cys are capable of releasing H2S from DATS and that DADS is a much poorer H2S donor than DATS.

Keywords: garlic-derived

polysulfide,

hydrogen

sulfide,

glutathione

2


perthiol, cysteine,

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1. Introduction Hydrogen sulfide (H2S) is a gasotransmitter molecule recognized for its role in cell signaling1-10 and its health benefits, particularly in reducing cardiovascular diseases.11-13 H2S can be produced by enzymes in human cells, or it can be promoted by the consumption of sulfur-containing diets. Synthetic H2S donors have been reported by many research groups to investigate the biological functions of H2S.14-21 Benavides et al. proposed that H2S production by garlic-based diets is strongly correlated with their beneficial vasoactivities.22 Two garlic-derived polysulfides, diallyl disulfide (DADS) and diallyl trisulfide (DATS), have been shown to release H2S in human red blood cells in the presence of biological thiols,22 and glutathione (GSH) has been observed to effectively induces the release of H2S from garlic. The reaction rate of liberating H2S by Cysteine (Cys) is slower.22 In buffer solution, the reactions of thiols

with DATS produce H2S more effectively than those with DADS,

while diallyl sulfide, allyl methyl sulfide and dipropyl disulfide are not reactive.22 H2S-liberating reactions between perthiol CysSSH and GSH to liberate were proposed based on experiments performed in cells.23-24 Very recently, experimental studies performed by Olson’s research group revealed that administering garlic oil to cells causes the release of H2S only when Cys or GSH are present in the extracellular medium.25 The mechanisms by which H2S is liberated from DADS or DATS have been investigated by several research groups.14, 17, 19, 22, 26 In buffer solutions, DADS can undergo α-carbon nucleophilic substitution with a thiol to form ASSH and ASR (RSH=Cys or GSH), or it can undergo thiol/disulfide exchange to form ASH (allyl mercaptan) and ASSR (see Scheme 1). In contrast, DATS can undergo thiol/disulfide exchange with thiol (GSH and Cys) to form allyl perthiol (ASSH). Furthermore, nucleophilic attack of a thiol on the α-carbon of DATS results in ASSSH and ASR. 3



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Thiol/disulfide exchange between a thiol and the central sulfur of DATS results in ASH and ASSSR, while thiol/disulfide exchange of a thiol and the peripheral sulfur results in ASSH and ASSR. H2S is liberated from the reaction of ASSH with Cys or GSH (Scheme 1).

Scheme 1. Proposed reaction routes involved in the reactions of DADS and DATS with thiols. However, the involvement of α-carbon nucleophilic substitution and the production of H2S (from ASSH) by DADS has been questioned. Huang et al. showed that DATS releases H2S instantly in the presence of GSH, while DADS only releases H2S sluggishly.26 It should be noted that it has been questioned whether H2S exhibits a cell signaling role. Instead, it has been proposed that sulfane sulfur, rather than H2S, is the active agent in physiological signaling.25, 27-31 Toohey proposed that a thiosulfoxide intermediate is produced and transfers its neutral (sulfane) sulfur to Cys, resulting in the perthiol of Cys (CysSSH).27 Persulfidation of a particular Cys residue in a target 4


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protein is proposed to facilitate cell signaling.7 Recently, Olson et al. revealed that H2S and polysulfides are formed from garlic oils in buffers and cells.25 The presence of GSH or Cys is necessary for H2S generation from garlic oil and DATS, while only polysulfides result from garlic oils. Furthermore, based on their cellular experiments, polysulfides were proposed by Olson et al. as the mediator for signaling functions instead of H2S.25 In this study, we aim to investigate the mechanism by which DADS and DATS react with biological thiols. Non-enzymatic methods of liberating H2S from garlic-derived compounds have attracted interest not only because these compounds demonstrate potential health benefits but also because mechanistic studies of these organic H2S donors could shed light on the production of H2S in biological systems.

2. Computational approach Three density functionals including the three-parameter hybrid generalized gradient approximation (GGA) exchange and correlation functional B3LYP32-33 and the meta-GGA Minnesota functionals M06 and M06-2X,34 were utilized in this work. The QB3 modification of the extrapolated complete basis set and correlation effects (CBS-QB3)35 was applied to methyl and allyl thiol species. The solvation effect of CPCM model was included in CBS-QB3 at the B3LYP/6-311(2d,d,p) level.35 A series of basis sets were used to compute pKa values. These basis sets include Pople’s

split-valence

basis

set

plus

polarization

and

diffuse

functions,

6-311G++(d,p),36-38 and Dunning’s correlation-consistent basis set with the augmented diffuse functions aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ.39-41 A conductor-like polarizable continuum model (CPCM) approach and its analytic gradients42 were used to model the solvation effects of water. The deprotonation free energies of thiols and perthiols were computed using the proton 5



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exchange scheme, i.e., the pKa of an acid BH was computed using

pK a ( BH ) = pK a ( AH ) +

∆Gsol , 2.303RT

(1)

where pK a ( AH ) is the experimentally determined pKa of an acid AH, and ∆Gsol is the solvated free energy of the following reaction

BH + A − → B − + AH .

(2)

The pKa values of thiols and hydropolysulfides (RSSH and RSSSH) were obtained using the experimental pKa of H2S (6.9). The potential energy surfaces were computed using B3LYP/6-311++G(d,p) on model systems. For the computations involving Cys and GSH, a moderate basis 6-31+G(d) was used. All transition states were verified with one imaginary vibrational frequency. The Gaussian 09 suite of programs were used in our studies.43

3. Results and Discussion pKa of thiols and perthiols. At physiological pH (7.4), 76% of H2S exists in the HS- form (pKa = 6.9), while the concentration of S2– is minimal. In the literature, H2S is often referred to total H2S plus HS– species in solution. The deprotonation of Cys and GSH correspond to the second and third pKa of Cys and GSH, respectively. The pKa values reveal that 10.5 % of Cys (pKa =8.33) and 5.2 % of GSH (pKa =8.66) exist in the anionic sulfide form (see Scheme 2). It is noted that, for polyprotic acid (Cys or GSH) our computed pKa corresponds to the lower one of the two microscopic pKa values of the acid.44

6


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Scheme 2. The protonation/deprotonation states of allyl mercaptan (ASH), Cys and GSH at physiological pH. The experimental pKa values of thiol groups are indicated. The basis set dependence of DFT computed pKa values of thiols and hydropolysulfides was investigated using the 6-311++G(d,p) and the aug-cc-pVXZ basis sets. We found that the pKa values computed with 6-311++G(d,p) basis set are similar to those computed using aug-cc-pVXZ basis sets (see Table S1, Supporting Information). The pKa values converge with the aug-cc-pVQZ basis set, in which sulfur consists of f and g type Gaussian polarization and diffuse functions. The pKa values of thiols and perthiols computed using the B3LYP/6-311++G(d,p) method are summarized in Table 1. The results of computations for simple thiol species using CBS-QB3 are summarized in the Table. Among the allyl thiol species, ASSSH is noticeably more acidic than ASSH, while ASH is the least acidic. At physiological pH, ASSSH and ASSH exist as their anionic forms ASSS– and ASS–, while ASH is relatively protonated. A similar trend was also observed for Cys and GSH, indicating that the biological −SSH and −SSSH 7



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functional groups exist predominantly in their anionic forms. Nucleophilic substitutions of thiol anion on S-atom (thiol/disulfide exchange) and on α-carbon of ally group of polysulfides. At physiological pH, a small percentage of the thiols exist in anionic form. Our proposal begins with the reactions of the thiol anions with DADS and DATS. Thiol anions may undergo two types of reaction with DADS and DATS: (1) nucleophilic substitution at the S-atom (thiol/disulfide exchange), or (2) nucleophilic substitution at the α-carbon. We began by using a model thiol anion, CH3S– to represent cysteine and glutathione thiol anions (CysS– and GS–). The potential energy surface (PES) for the reactions of CH3S- with DADS is illustrated in Fig. 1. The relative energies (Gibbs free energy at 298 K, including the solvation effects of water) of the reacting species are shown with respect to those of free DADS and CH3S–. The pre-reaction complex (CH3S–…DADS) lies 4.3 kcal/mol above the free reacting species. The transition state (TS) in the nucleophilic attack of CH3S– on the S-atom of DADS lies at 15.8 kcal/mol on PES. The reaction leads to the formation of AS–…ASSCH3 complex (5.1 kcal/mol on PES), then to free AS– and ASSCH3 (-1.7 kcal/mol). In contrast, the TS for nucleophilic substitutions on the α- and γ-carbons of DADS lies noticeably higher in energy (29.3 and 31.3 kcal/mol, respectively) than that of the nucleophilic attack on the S-atom. Furthermore, it is seen that the ASS–…ASCH3 complex is lower in energy than AS–…ASSCH3. Similarly, for the free species, the ASS– + ASCH3 complex is lower in energy than AS– + ASSCH3. The PES for the reactions of CH3S– with DATS is illustrated in Fig. 2, which shows that the nucleophilic attack of CH3S– on the peripheral S-atom of DATS involves a smaller barrier (12.3 kcal/mol) than that on the central S-atom (15.1 kcal/mol) of DATS. The magnitudes of the imaginary frequencies of the TSs involving in the aforementioned reactions are very low: 98 i and 125 i cm-1, 8


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respectively. The products of CH3S– attack on peripheral sulfur, ASSCH3 + ASS– is lower in energy than those resulted from CH3S– attack on central sulfur, i.e., ASSSCH3 + AS–. As for the reactions of DADS, we found that α-carbon attack by CH3S– involves a high barrier, while γ-carbon attack involves an even higher reaction barrier. In contrast, the product of γ-carbon is an episulfide, which is 2.4 kcal/mol higher in energy than ASSCH3. ASCH3 + ASSS– are the lowest energy products, despite the high energy barrier involved in their formation. The energy profiles for the reactions of DADS and DATS with CysS– and GS– are illustrated in Fig. 3. The PESs of the reactions begin with the pre-reaction complexes and finish with complexes of the products. Nucleophilic attack on the γ-carbons of DADS and DATS was not attempted in these reactions. Two interesting features were observed in the reactions of CysS– and GS– with DADS and DATS. First, nucleophilic S-attacks by GS- on DADS and DATS are kinetically and thermodynamically more favorable than those by CysS–. Secondly, nucleophilic S-atom attack on the peripheral sulfur of DATS is energetically favorable than that on the central sulfur. The perthiol anion ASS–, which plays a key role in H2S release results from the reactions between thiol anions and DATS. Our computed PESs reveal that GS- releases ASS– from DATS more effectively than CysS–, both from kinetic and thermodynamic perspectives. As in our observations of the model species, we found that the TSs of the nucleophilic attacks by thiol anions on the α-carbons of DADS [Fig. 3(a) and 3(b)] and DATS [Fig. 3(c) and 3(d)] are significantly higher in energy than those of nucleophilic attacks by thiol anions on sulfur atoms. Comparatively, TSs involving GS– are lower in energy than those of their CysS– counterparts. The release of H2S by reaction of ASSH/ASS- with Cys or GSH. Allyl perthiol 9



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ASSH has a relatively low pKa. Thus, it exists mainly in the anionic form at physiological pH. In the presence of Cys or GSH, ASS– could undergo nucleophilic attack on the carbon of these thiols to release HS–. However, this was shown to be very unlikely because a nucleophilic attack on the carbon atoms of Cys and GSH by ASS– to release H2S involves very high reaction barriers (vide infra). An alternative pathway involves an endergonic proton transfer from the thiol to ASS–, followed by nucleophilic attack of a thiol anion on ASSH to release HS-. The PESs for the reactions of CH3SH and ASS– are illustrated in Fig. 4. Nucleophilic attack on CH3SH by ASS– to liberate H2S involves a barrier of up to 28.5 kcal/mol. Alternatively, the ASS–…HSCH3 complex experiences an ascending PES of 8.8 kcal/mol to form ASSH…–SCH3. CH3S– then undergoes nucleophilic attack on the S-atom of ASSH, overcoming a barrier of 15.3 kcal/mol on the PES to form ASSCH3…HS–. Alternatively, CH3S– could react with another TS at 12.5 kcal/mol on the PES to form CH3SSH…AS–, which is then completed by another S-atom attack by AS- on CH3SSH to release H2S. It is noticed that the imaginary frequencies involved in the TSs are very small in magnitudes. The PES for the scan of the proton shuffled from CH3SH to ASS– is shown in Fig. S4. The extremely shallow energy surface means that attempts to locate the TSs for the proton transfer from Cys and GSH to ASS– were unsuccessful. A PES scan along the reaction coordinate reveals that it is barrier-less. For CysS– [Fig. 5(a)], S-atom nucleophilic attack on the inner S-atom of ASSH, resulting in HS– and ASSCys, is kinetically favorable (TS is 14.3 kcal/mol on PES) than the nucleophilic attack on the terminal S-atom of ASSH (15.3 kcal/mol). The latter reaction results in the AS–…CysSSH complex, which experiences a small barrier (13.4 kcal/mol on PES) for AS– attack on CysSSH to release HS–. In contrast, the S-atom nucleophilic attack of GS– on the inner S-atom of ASSH [Fig. 5(b)] involves a slightly higher barrier (17.7 10


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kcal/mol) than the nucleophilic attack on the terminal S-atom of ASSH (16.4 kcal/mol). However, the latter reaction involves a high barrier (22.1 kcal/mol) for the attack of for AS– attack on GSSH to release HS–. By comparison, the reaction of Cys with ASS– to release HS– is more kinetically and thermodynamically favored than that of GSH. The direct nucleophilic attack of ASS– on CysSH and GSH to release HS– involves very high energy TSs, the reaction barriers are 34.8 and 38.6 kcal/mol, respectively. Our investigation reveals that H2S/HS– is most efficiently liberated from the central sulfur of DATS by biological thiols Cys and GSH. These thiols are weak acids, and only a few percent of them exist in anionic form at physiological pH. Nucleophilic substitution of the thiol anion on the peripheral S-atom result in allyl perthiol (ASSH/ASS–). ASS– accepts a proton from Cys or GSH, causing H2S/HS– to be released by an S-atom attack from CysS– or GSHS–. ASS– can be released from DADS via α-carbon attack by a thiol anion. However, the reaction rate is significantly smaller. It was demonstrated by Benavides et al. that GSH has a higher potency to release H2S from DATS than Cys in buffer solution.22 In contrast, experiments performed by Olson et al. reveals that both thiols are nearly equally potent, while Cys is slightly more effective.25 Our predicted PESs reveals that GSH is more potent in releasing perthiol anion ASS–, while Cys is more effective in the releasing HS– from ASS–. The mechanism predicted from our study also suggests that H2S release rate is pH sensitive. Mechanism of H2S liberation from ASSH revealed in this study may shed light on

experimental observations.17-18, 22, 25-26 The reaction pathways (using GSH)

are summarized in Scheme 3, in which the dashed, solid, and bold arrows indicate the order of likeliness, from the least to the most likely, respectively.

11



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SS

S

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-

+ GS-

S

SSG

S

+

SSS

S

SG

+

-

SG

+

S S

+ GSSSSG

SSG

S

+

-

-

SS

+

+ GSH S

+ GSSH GS-

SSG

+

HSS

HS-

Scheme 3. Reaction pathways (using GSH) involved in the reactions of biological thiols with DADS and DATS. The dashed, solid, and bold arrows indicate the order of likeliness, from the least to the most likely, respectively.

4. Conclusion We propose that Cys and GSH react with garlic-derived polysulfides in their anionic forms. The nucleophilic substitution of thiol anions on the S-atom of DADS and DATS involve significantly lower barriers than those for nucleophilic substitutions on the α-carbons of allyl groups. The dithiol anion (ASS–) resulted from the reaction of thiol anions with DATS. ASS- receives a proton from a second thiol, i.e., Cys or GSH. The thiol anion then undergoes nucleophilic substitution on ASSH to liberate H2S (HS–). Since a nucleophilic attack on an α-carbon is required for DADS to form ASSH, its capacity to release H2S is predicted to be slower than that of 12


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DATS.

Acknowledgement. The authors acknowledge that the National Science Council of Taiwan, Republic of China, supported this work under Grant No. MOST 104-2113-M-018 -004.

Supporting Information Available: Total energies, pKa values, and complete potential energy surfaces of reactions are summarized. The materials are available, free of charge, via Internet at http://pubs.acs.org.

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29. Liu, C.; Zhang, F.; Munske, G.; Zhang, H.; Xian, M. Isotope Dilution Mass Spectrometry for the Quantification of Sulfane Sulfurs. Free Radic. Bio. Med. 2014, 76, 200-207. 30. Yagdi, E.; Cerella, C.; Dicato, M.; Diederich, M. Garlic-derived Natural Polysulfanes as Hydrogen Sulfide Donors: Friend or Foe? Food Chem. Toxicol. 2016, 95, 219-233. 31. Toohey, J. I. The Conversion of H(2)S to Sulfane Sulfur. Nat. Rev. Mol. Cell Biol. 2012, 13, 803. 32. Becke, A. D. Density-functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648-5652. 33. Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti Correlation Energy Formula into a Functional of Electron Density. Phys. Rev. B 1988, 37, 785-789. 34. Zhao, Y.; Truhlar, D. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 other Functionals. Theo. Chem. Acc. 2008, 120, 215-241. 35. Montgomery, J. A. J.; Frisch, M. J.; Ochterski, J. W.; Petersson, G. A. A complete basis set model chemistry. VI. Use of Density Functional Geometries and Frequencies. J. Chem. Phys. 1999, 110, 2822-2827. 36. Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. Self‐consistent Molecular Orbital Methods. XX. A Basis Set for Correlated Wave Functions. J. Chem. Phys. 1980, 72, 650-654. 37. Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. v. R. Efficient Diffuse Function-augmented Basis-sets for Anion Calculations. 3. The 3-21+G Basis Set for 1st-row Elements, Li-F. J. Comp. Chem. 1983, 4, 294-301. 38. Frisch, M. J.; Pople, J. A.; Binkley, J. S. Self‐consistent Molecular Orbital Methods 25. Supplementary Functions for Gaussian Basis Sets. J. Chem. Phys. 1984, 80, 3265-3269. 39. Dunning, T. H. J. Gaussian Basis Sets for Use in Correlated Molecular Calculations. I. The Atoms Boron through Neon and Hydrogen. J. Chem. Phys. 1989, 90, 1007-1023. 40. Kendall, R. A.; Dunning, T. H. J.; Harrison, R. J. Electron Affinities of the First‐ row Atoms Revisited. Systematic Basis Sets and Wave Functions. J. Chem. Phys. 1992, 96, 6796-6806. 41. Woon, D. E.; Dunning, T. H. J. Gaussian Basis Sets for Use in Correlated Molecular Calculations. III. The Atoms Aluminum through Argon. J. Chem. Phys. 16


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Page 18 of 26

Table 1. Computed pKa values of sulfides and hydropolysulfides. The 6-311++G(d,p) basis set was used in DFT computations. B3LYP

M06

M06-2X

CBS-QB3

ASH

8.3 (exp 9.74)

6.4

7.9

8.8

ASSH

5.6

4.8

5.5

6.3

ASSSH

3.4

2.6

2.9

4.1

Cys

10.7 (exp 8.33)

9.8

11.2

CysSSH

3.5

3.2

2.8

CysSSSH

-0.5

0.1

-2.5

GSH

9.3 (exp 8.66)

7.2

3.0

GSSH

-0.1

-1.6

-0.1

GSSSH

-1.5

-6.1

-4.0

18


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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


2.30 2.15

vimg =346 i

31.3 30 29.3

2.56 2.46

15.8

15

vimg =412 i

10 5 0.0 0

5.1

4.3 CH3

S-

AS-

CH3SSA

DADS

CH3S- + DADS

-1.7

AS- + CH3SSA

-7.5

ASS- + CH3SA

-3.2 ASS-

-5

CH3SA

2.43 2.57

vimg =135 i

Figure 1. Potential energy surface for the reactions of CH3S- with DADS.

19



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Page 20 of 26

2.25 2.27 vimg=252 i

2.63

29.7 2.47

vimg=381 i

2.60

vimg=125 i

10

2.47

26.8

25

CH3S-

DATS 6.1

15.1 1.86

12.3 AS-

5 ASS- CH3SSA (episulfide)

0.0 0

CH3S- + DATS

ASS-

-5 2.78

-10

2.30

CH3SSA ASSS-

CH3SSSA

4.1 2.9 -1.4 -5.2 CH3SA

1.85

episulfide -2.2 -4.8 -7.2

AS- + CH3SSSA ASS- + CH3SSA (episulfide) ASS- + CH3SSA

-10.5

ASSS- + CH3SA

vimg=98 i

Figure 2. Potential energy surface for the reactions of CH3S- with DATS.

20


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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


2.53

30

28.1

15

15.2

2.51

vimg =402 i

11.0 10

AS

5

2.71

CysSSA

2.34

4.0 ASS- CysSA

0.0 0

-

CysS -

DADS

-5

(a)

(b) 21


vimg =114 i


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

(c)

22


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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


2.54 2.48 vimg=399 i

25

2.43

21.6

2.66

20 10.5 6.9

10

vimg =110 i

5 0 -5 -10

-3.8 AS-

0.0 GS-

DATS

-8.8 ASS-

2.43 2.57

GSSSA vimg =126 i

GSSA

-11.5 ASSS- GSA

(d) Figure 3. The energy profiles for the reactions of DADS with (a) CysS- and (b) GS-; and the energy profiles for the reactions of DATS with (c) CysS- and (d) GS-.

23



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Page 24 of 26

2.44 2.45

vimg =517 i

30

2.25

2.90

28.5

2.75 2.33

25

vimg =91 i

15.3 15

vimg=124 i

13.4

12.5

10

8.8

5

CH3S-

5.8

ASSH AS

0

-

CH3SSH

0.0 ASS- CH3SH

2.39 2.60

-5

-4.6 HS-

vimg =98 i

Figure 4. The energy profiles for the reactions of ASS- with CH3SH.

24


CH3SSA

Page 25 of 26

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


2.50 2.51 2.29

2.75 vimg =473 i

vimg =132 i

2.49

34.8

35

2.52

30 15.3 15

vimg =132 i

13.4 14.3 9.7

10 6.9 5 0

AS- CysSSH

CysS - ASSH 0.0 ASS- CysSH

-2.2

-5

HS- CysSSA

2.62 2.41

vimg =118 i

(a)

(b) Figure 5.

The energy profiles for the reactions of ASS- with (a) Cys and (b) GSH.

25



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Table of Contents Graphic:

26


Page 26 of 26

Computational Study of H2S Release in Reactions of Diallyl

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