Computational study of the hydrogen peroxide scavenging mechanism of allyl methyl disulfide, an antioxidant compound from garlic

Abstract

Although many sulfur containing garlic compounds present antioxidant activity, little is known about molecular mechanisms through which these compounds react with reactive oxygen species. In this work, the reactivity and the hydrogen peroxide scavenger reaction mechanisms (including thermodynamics and kinetics aspects) of allyl methyl disulfide in aqueous phase are studied employing density functional theory computational methods. Three reactive sites susceptible for electrophilic attack are found over sulfur atoms and the double bond allyl moiety. For each detected site, one redox reaction is proposed and analyzed. All reactions are thermodynamically feasible, whereas attack over the methyl bound sulfur atom is kinetically favored.

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References

  1. 1.

    Manda G, Nechifor MT, Neagu T (2009) Reactive oxygen species, cancer and anti-cancer therapies. Curr Chem Biol 3:342–366. https://doi.org/10.2174/187231309787158271

    CAS  Article  Google Scholar 

  2. 2.

    D’Autréaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824. https://doi.org/10.1038/nrm2256

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Kirkinezos IG, Moraes CT (2001) Reactive oxygen species and mitochondrial diseases. Semin Cell Dev Biol 12:449–457. https://doi.org/10.1006/scdb.2001.0282

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Hancock JT, Desikan R, Neill SJ (2001) Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 29:345–350. https://doi.org/10.1042/0300-5127:0290345

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Vaidya V, Ingold KU, Pratt DA (2009) Garlic: source of the ultimate antioxidants-sulfenic acids. Angew Chemie Int Ed 48:157–160. https://doi.org/10.1002/anie.200804560

    CAS  Article  Google Scholar 

  6. 6.

    Chauvin J-PR, Pratt DA (2017) On the reactions of thiols, sulfenic acids, and sulfinic acids with hydrogen peroxide. Angew Chemie Int Ed 56:6255–6259. https://doi.org/10.1002/anie.201610402

    CAS  Article  Google Scholar 

  7. 7.

    Leelarungrayub N, Rattanapanone V, Chanarat N, Gebicki JM (2006) Quantitative evaluation of the antioxidant properties of garlic and shallot preparations. Nutrition 22:266–274. https://doi.org/10.1016/j.nut.2005.05.010

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Amagase H, Petesch BL, Matsuura H et al (2001) Intake of garlic and its bioactive components. J Nutr 131:955S–962S

    CAS  Article  Google Scholar 

  9. 9.

    Queiroz YS, Ishimoto EY, Bastos DHM et al (2009) Garlic (Allium sativum L.) and ready-to-eat garlic products: in vitro antioxidant activity. Food Chem 115:371–374. https://doi.org/10.1016/j.foodchem.2008.11.105

    CAS  Article  Google Scholar 

  10. 10.

    Omar SH, Al-Wabel NA (2010) Organosulfur compounds and possible mechanism of garlic in cancer. Saudi Pharm J 18:51–58. https://doi.org/10.1016/j.jsps.2009.12.007

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Munday R (2012) Harmful and beneficial effects of organic monosulfides, disulfides, and polysulfides in animals and humans. Chem Res Toxicol 25:47–60. https://doi.org/10.1021/tx200373u

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Premdas PD, Bowers RJ, Forkert P (2000) Inactivation of hepatic CYP2E1 by an epoxide of diallyl. J Pharmacol Exp Ther 293:1112–1120

    CAS  PubMed  Google Scholar 

  13. 13.

    Andrada MF, Martínez JCG, Szori M et al (2008) Thermodynamics of competing oxidation reactions of allyl methyl disulfide by hydrogen peroxide: a first principle molecular computational study on the conformations of allyl methyl disulfide and its oxidized products. J Phys Org Chem 21:1048–1058. https://doi.org/10.1002/poc.1398

    CAS  Article  Google Scholar 

  14. 14.

    Ingold KU, Pratt DA (2014) Advances in radical-trapping antioxidant chemistry in the 21st Century: a kinetics and mechanisms perspective. Chem Rev 114:9022–9046. https://doi.org/10.1021/cr500226n

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Chauvin J-PR, Zielinski ZAM, Pratt DA (2016) Inspired by garlic: insights on the chemistry of sulfenic acids and the radical-trapping antioxidant activity of organosulfur compounds. Can J Chem 94:1–8. https://doi.org/10.1139/cjc-2015-0438

    CAS  Article  Google Scholar 

  16. 16.

    Galano A, Mazzone G, Alvarez-Diduk R et al (2016) Food antioxidants: chemical insights at the molecular level. Annu Rev Food Sci Technol 7:335–352. https://doi.org/10.1146/annurev-food-041715-033206

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    van Bergen LAH, Roos G, De Proft F (2014) From thiol to sulfonic acid: modeling the oxidation pathway of protein thiols by hydrogen peroxide. J Phys Chem A 118:6078–6084. https://doi.org/10.1021/jp5018339

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Zeida A, Babbush R, González Lebrero MC et al (2012) Molecular basis of the mechanism of thiol oxidation by hydrogen peroxide in aqueous solution: challenging the SN2 Paradigm. Chem Res Toxicol 25:741–746. https://doi.org/10.1021/tx200540z

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Cardey B, Enescu M (2005) A computational study of thiolate and selenolate oxidation by hydrogen peroxide. ChemPhysChem 6:1175–1180. https://doi.org/10.1002/cphc.200400568

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, RevisionD.01. Gaussian, Inc., Wallingford CT

  21. 21.

    Glendening ED, Reed AE, Carpenter JE, Weinhold F (1993) NBO Version 3.1

  22. 22.

    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    CAS  Article  Google Scholar 

  23. 23.

    Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    CAS  Article  Google Scholar 

  24. 24.

    Zhao Y, Schultz NE, Truhlar DG (2006) Design of density functionals by combining the method of constraint satisfaction with parametrization for thermochemistry, thermochemical kinetics, and noncovalent interactions. J Chem Theory Comput. https://doi.org/10.1021/CT0502763

    Article  PubMed  Google Scholar 

  25. 25.

    Leyssens T, Peeters D (2004) Theoretical study of the properties of phosphonate. J Mol Struct THEOCHEM 673:79–86. https://doi.org/10.1016/j.theochem.2003.12.001

    CAS  Article  Google Scholar 

  26. 26.

    Vandermeeren L, Leyssens T, Peeters D (2007) Theoretical study of the properties of sulfone and sulfoxide functional groups. J Mol Struct THEOCHEM 804:1–8. https://doi.org/10.1016/j.theochem.2006.10.006

    CAS  Article  Google Scholar 

  27. 27.

    Vega-Hissi EG, Andrada MF, Zamarbide GN et al (2011) Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis. J Mol Model 17:1317–1323. https://doi.org/10.1007/s00894-010-0829-y

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Halgren TA, Lipscomb WN (1977) The synchronous-transit method for determining reaction pathways and locating molecular transition states. Chem Phys Lett 49:225–232. https://doi.org/10.1016/0009-2614(77)80574-5

    CAS  Article  Google Scholar 

  29. 29.

    Peng C, Schlegel Bernhard H (1993) Combining synchronous transit and quasi-newton methods to find transition states. Isr J Chem 33:449–454. https://doi.org/10.1002/ijch.199300051

    CAS  Article  Google Scholar 

  30. 30.

    Fukui K (1981) The path of chemical reactions: the IRC approach. Acc Chem Res 14:363–368. https://doi.org/10.1021/ar00072a001

    CAS  Article  Google Scholar 

  31. 31.

    Boys SF, Bernardi F (1970) The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 19:553–566. https://doi.org/10.1080/00268977000101561

    CAS  Article  Google Scholar 

  32. 32.

    Wigner E (1932) On the quantum correction for thermodynamic equilibrium. Phys Rev 40:749–759. https://doi.org/10.1103/PhysRev.40.749

    CAS  Article  Google Scholar 

  33. 33.

    Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396. https://doi.org/10.1021/jp810292n

    CAS  Article  Google Scholar 

  34. 34.

    Tomasi J, Persico M (1994) Molecular interactions in solution: an overview of methods based on continuous distributions of the solvent. Chem Rev 94:2027–2094. https://doi.org/10.1021/cr00031a013

    CAS  Article  Google Scholar 

  35. 35.

    Cossi M, Barone V, Cammi R, Tomasi J (1996) Ab initio study of solvated molecules: a new implementation of the polarizable continuum model. Chem Phys Lett 255:327–335. https://doi.org/10.1016/0009-2614(96)00349-1

    CAS  Article  Google Scholar 

  36. 36.

    Liptak MD, Shields GC (2001) Experimentation with different thermodynamic cycles used for pKa calculations on carboxylic acids using complete basis set and Gaussian-n models combined with CPCM continuum solvation methods. Int J Quantum Chem 85:727–741. https://doi.org/10.1002/qua.1703

    CAS  Article  Google Scholar 

  37. 37.

    Namazian M, Zare HR, Coote ML (2008) Determination of the absolute redox potential of Rutin: experimental and theoretical studies. Biophys Chem 132:64–68. https://doi.org/10.1016/j.bpc.2007.10.010

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Parr RG, Yang W (1984) Density functional approach to the frontier-electron theory of chemical reactivity. J Am Chem Soc 106:4049–4050. https://doi.org/10.1021/ja00326a036

    CAS  Article  Google Scholar 

  39. 39.

    Davidson ER, Chakravorty S (1992) A test of the Hirshfeld definition of atomic charges and moments. Theor Chim Acta 83:319–330. https://doi.org/10.1007/BF01113058

    CAS  Article  Google Scholar 

  40. 40.

    Rousseau B, Peeters A, Van Alsenoy C (2000) Systematic study of the parameters determining stockholder charges. Chem Phys Lett 324:189–194. https://doi.org/10.1016/S0009-2614(00)00585-6

    CAS  Article  Google Scholar 

  41. 41.

    Oláh J, Van Alsenoy C, Sannigrahi AB (2002) Condensed Fukui functions derived from stockholder charges: assessment of their performance as local reactivity descriptors. J Phys Chem A 106:3885–3890. https://doi.org/10.1021/JP014039H

    Article  Google Scholar 

  42. 42.

    Morell C, Grand A, Toro-Labbé A (2005) New dual descriptor for chemical reactivity. J Phys Chem A 109:205–212. https://doi.org/10.1021/jp046577a

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Lu T, Chen F (2012) Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33:580–592. https://doi.org/10.1002/jcc.22885

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    De Luca G, Sicilia E, Russo N, Mineva T (2002) On the hardness evaluation in solvent for neutral and charged systems. J Am Chem Soc 124:1494–1499. https://doi.org/10.1021/ja0116977

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Zhang J, Wang C, Ji L, Liu W (2016) Modeling of toxicity-relevant electrophilic reactivity for guanine with epoxides: estimating the hard and soft acids and bases (HSAB) parameter as a predictor. Chem Res Toxicol 29:841–850. https://doi.org/10.1021/acs.chemrestox.6b00018

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Forkert PG, Premdas PD, Bowers RJ (2000) Epoxide formation from diallyl sulfone is associated with CYP2E1 inactivation in murine and human lungs. Am J Respir Cell Mol Biol 23:687–695. https://doi.org/10.1165/ajrcmb.23.5.4149

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Chu J-W, Trout BL (2004) On the mechanisms of oxidation of organic sulfides by H2O2 in aqueous solutions. J Am Chem Soc 126:900–908. https://doi.org/10.1021/JA036762M

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Bayse CA (2011) Transition states for cysteine redox processes modeled by DFT and solvent-assisted proton exchange. Org Biomol Chem 9:4748. https://doi.org/10.1039/c1ob05497j

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank UNSL and CONICET for the financial support. JCGM and EGVH are members of the Scientific Research Career of CONICET. MGD is fellow of CONICET.

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Correspondence to Esteban G. Vega-Hissi.

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Vega-Hissi, E.G., Andrada, M.F., Díaz, M.G. et al. Computational study of the hydrogen peroxide scavenging mechanism of allyl methyl disulfide, an antioxidant compound from garlic. Mol Divers 23, 985–995 (2019). https://doi.org/10.1007/s11030-019-09927-6

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Keywords

  • Computational modeling
  • Reactivity
  • Reaction mechanism
  • Oxidation
  • Hydrogen peroxide
  • Garlic disulfide compound
  • Density functional