Nucleophilic substitution vs elimination reaction of bisulfide ions with substituted methanes: exploration of chiral selectivity by stereodirectional first-principles dynamics and transition state theory

  • Marcos Vinícius C. S. Rezende
  • Nayara D. CoutinhoEmail author
  • Federico Palazzetti
  • Andrea Lombardi
  • Valter Henrique Carvalho-SilvaEmail author
Original Paper
Part of the following topical collections:
  1. VII Symposium on Electronic Structure and Molecular Dynamics – VII SeedMol


Control of molecular orientation is emerging as crucial for the characterization of the stereodynamics of kinetics processes beyond structural stereochemistry. The special role played in chiral discrimination phenomena has been particularly emphasized by Aquilanti and collaborators after their extensive probes of experimental control of molecular alignment and orientation. In this work, the manifestation of the Aquilanti mechanism has been demonstrated for the first time in first-principles molecular dynamics simulations: stationary points characterized on potential energy surfaces have been calculated for the study of chemical reactions occurring between the bisulfide anion HS and oriented prototypical chiral molecules CHFXY (where X = CH3 or CN and Y = Cl or I). The important reaction channels are those corresponding to bimolecular nucleophilic substitution (SN2) and to bimolecular elimination (E2): their relative role has been assessed and alternative pathways due to the mirror forms of the oriented chiral molecule are revealed by the different reactivity of the two enantiomers of CHFCNI in SN2 reaction.


DFT d-TST Chiral discrimination BOMD 



The authors are grateful for the support given by Brazilian CAPES and CNPq and by High-Performance Computing Center at the Universidade Estadual de Goiás (UEG). Valter H. Carvalho-Silva thanks CNPq for the research funding programs [Universal 01/2016 - Faixa A - 406063/2016-8] and Organizzazione Internazionale Italo-Latino Americana (IILA) for Biotechnology Sector-2019 scholarship. Federico Palazzetti, Nayara D. Coutinho, and Andrea Lombardi acknowledge the Italian Ministry for Education, University and Research, MIUR, for financial support: SIR 2014 “Scientific Independence for young Researchers” (RBSI14U3VF). We thank Vincenzo Aquilanti for fruitful discussions.

Supplementary material

894_2019_4126_MOESM1_ESM.docx (35 kb)
ESM 1 (DOCX 35 kb)


  1. 1.
    Aquilanti V, Grossi G, Lombardi A, Maciel GS (2008) The origin of chiral discrimination : supersonic molecular beam experiments and molecular dynamics simulations of collisional mechanisms. Phys Scr 78:58119. CrossRefGoogle Scholar
  2. 2.
    Aquilanti V, Maciel GS (2006) Observed molecular alignment in gaseous streams and possible chiral effects in vortices and in surface scattering. Orig Life Evol Biosph 36:435–441. CrossRefPubMedGoogle Scholar
  3. 3.
    Kasai T, Che D-CD-C, Okada M et al (2014) Directions of chemical change: experimental characterization of the stereodynamics of photodissociation and reactive processes. Phys Chem Chem Phys 16:9776. CrossRefPubMedGoogle Scholar
  4. 4.
    Palazzetti F, Maciel GSGS, Lombardi A et al (2012) The astrochemical observatory: molecules in the laboratory and in the cosmos. J Chin Chem Soc 59:1045–1052. CrossRefGoogle Scholar
  5. 5.
    Aquilanti V, Caglioti C, Casavecchia P, et al (2017) The astrochemical observatory: computational and theoretical focus on molecular chirality changing torsions around O-O and S-S bonds. In: AIP Conference Proceedings. p 030010Google Scholar
  6. 6.
    Bergman P, Parise B, Liseau R et al (2011) Detection of interstellar hydrogen peroxide. Astron Astrophys 531:L8. CrossRefGoogle Scholar
  7. 7.
    McGuire BA, Brandon Carroll P, Loomis RA, Finneran IA, Jewell PR, Remijan AJ, GAB (2016) Discovery of the interstellar chiralmolecule propylene oxide (CH3CHCH2O). Science 352:1449–1452CrossRefGoogle Scholar
  8. 8.
    Lombardi A, Palazzetti F (2018) Chirality in molecular collision dynamics. J Phys Condens Matter 30:063003. CrossRefPubMedGoogle Scholar
  9. 9.
    Lombardi A, Maciel GS, Palazzetti F et al (2010) Alignment and chirality in gaseous flows. J Vac Soc Jpn 53:645–653. CrossRefGoogle Scholar
  10. 10.
    Aquilanti V, Grossi G, Lombardi A et al (2011) Aligned molecular collisions and a stereodynamical mechanism for selective chirality. Rendiconti Lincei 22:125–135. CrossRefGoogle Scholar
  11. 11.
    Aquilanti V, Bartolomei M, Pirani F et al (2005) Orienting and aligning molecules for stereochemistry and photodynamics. Nature 7:291–300. CrossRefGoogle Scholar
  12. 12.
    Aquilanti V, Ascenzi D, Cappelletti D, Pirani F (1994) Velocity dependence of collisional alignment of oxygen molecules in gaseous expansions. Nature 371:399–402. CrossRefGoogle Scholar
  13. 13.
    Aquilanti V, Ascenzi D, Cappelletti D, F (1995) Rotational alignment in supersonic seeded beams of molecular oxygen. J Phys 99:13620–13626. CrossRefGoogle Scholar
  14. 14.
    Aquilanti V, Ascenzi D, Fedeli R et al (2002) Molecular beam scattering of nitrogen molecules in supersonic seeded beams: a probe of rotational alignment. J Phys Chem A 101:7648–7656. CrossRefGoogle Scholar
  15. 15.
    Pirani F, Cappelletti D, Bartolomei M et al (2001) Orientation of benzene in supersonic expansions, probed by IR-laser absorption and by molecular beam scattering. Phys Rev Lett 86:5035–5038. CrossRefPubMedGoogle Scholar
  16. 16.
    Cappelletti D, Bartolomei M, Aquilanti V et al (2006) Alignment of ethylene molecules in supersonic seeded expansions probed by infrared polarized laser absorption and by molecular beam scattering. Chem Phys Lett 420:47–53. CrossRefGoogle Scholar
  17. 17.
    Orientation C, Lee HN, Su TM, Chao I (2004) Rotamer dynamics of substituted simple alkanes. 1. A classical trajectory study of collisional orientation and alignment of 1-bromo-2-chloroethane with argon. J Phys Chem A 108:2567–2575. CrossRefGoogle Scholar
  18. 18.
    Lee HN, Chang LC, Su TM (2011) Optical rotamers of substituted simple alkanes induced by macroscopic translation-rotational motions. Chem Phys Lett 507:63–68. CrossRefGoogle Scholar
  19. 19.
    Lee HN, Chao I, Su TM (2011) Asymmetry in the internal energies of the optical rotamers of 1-bromo-2-chloroethane in oriented-molecule/surface scattering: a classical molecular dynamics study. Chem Phys Lett 517:132–138. CrossRefGoogle Scholar
  20. 20.
    Su TM, Palazzetti F, Lombardi A et al (2013) Molecular alignment and chirality in gaseous streams and vortices. Rendiconti Lincei 24:291–297. CrossRefGoogle Scholar
  21. 21.
    Che D-C, Palazzetti F, Okuno Y et al (2010) Electrostatic hexapole state-selection of the asymmetric-top molecule propylene oxide. J Phys Chem A 114:3280–3286. CrossRefPubMedGoogle Scholar
  22. 22.
    Che D, Kanda K, Palazzetti F et al (2012) Electrostatic hexapole state-selection of the asymmetric-top molecule propylene oxide: rotational and orientational distributions. Chem Phys 399:180–192. CrossRefGoogle Scholar
  23. 23.
    Palazzetti F, Maciel GS, Kanda K et al (2014) Control of conformers combining cooling by supersonic expansion of seeded molecular beams with hexapole selection and alignment: experiment and theory on 2-butanol. Phys Chem Chem Phys 16:9866–9875. CrossRefPubMedGoogle Scholar
  24. 24.
    Nakamura M, Yang SJ, Tsai PY et al (2016) Hexapole-oriented asymmetric-top molecules and their stereodirectional photodissociation dynamics. J Phys Chem A 120:5389–5398. CrossRefPubMedGoogle Scholar
  25. 25.
    Nakamura M, Yang S-J, Lin K-C et al (2017) Stereodirectional images of molecules oriented by a variable-voltage hexapolar field: fragmentation channels of 2-bromobutane electronically excited at two photolysis wavelengths. J Chem Phys 147:013917. CrossRefPubMedGoogle Scholar
  26. 26.
    Nakamura M, Palazzetti F, Tsai P-Y et al (2018) Vectorial imaging of the photodissociation of 2-bromobutane oriented via hexapolar state selection. Phys Chem Chem Phys. CrossRefGoogle Scholar
  27. 27.
    Lombardi A, Palazzetti F, Maciel GS et al (2011) Simulation of oriented collision dynamics of simple chiral molecules. Int J Quantum Chem 111:1651–1658. CrossRefGoogle Scholar
  28. 28.
    Barreto PRPRP, Vilela AFAAFA, Lombardi A et al (2007) The hydrogen peroxide-rare gas systems: quantum chemical calculations and hyperspherical harmonic representation of the potential energy surface for atom-floppy molecule interactions. J Phys Chem A 111:12754–12762. CrossRefPubMedGoogle Scholar
  29. 29.
    Só YA O, de Neto PH, O, de Macedo LGM, Gargano R (2019) Theoretical investigation on H2O2-Ng (He, Ne, Ar, Kr, Xe, and Rn) complexes suitable for stereodynamics: interactions and thermal chiral rate consequences. Front Chem 6:1–11.
  30. 30.
    Maciel GS, Barreto PRP, Palazzetti F et al (2008) A quantum chemical study of H2S2: intramolecular torsional mode and intermolecular interactions with rare gases. J Chem Phys 129:164302. CrossRefPubMedGoogle Scholar
  31. 31.
    Palazzetti F, Tsai PY, Lombardi A et al (2013) Aligned molecules: chirality discrimination in photodissociation and in molecular dynamics. Rendiconti Lincei 24:299–308. CrossRefGoogle Scholar
  32. 32.
    Gronert S (2003) Gas phase studies of the competition between substitution and elimination reactions. Acc Chem Res 36:848–857. CrossRefPubMedGoogle Scholar
  33. 33.
    Regan CK (2002) Steric effects and solvent effects in ionic reactions. Science 295:2245–2247. CrossRefPubMedGoogle Scholar
  34. 34.
    Ensing B, Klein ML (2005) Perspective on the reactions between F and CH3CH2F: the free energy landscape of the E2 and SN2 reaction channels. In: Proceedings of the National Academy of Sciences. pp 6755–6759Google Scholar
  35. 35.
    Hu W-P, Truhlar DG (1996) Factors affecting competitive ion−molecule reactions: ClO + C2H5 Cl and C2D5 Cl via E2 and SN2 channels. J Am Chem Soc 118:860–869. CrossRefGoogle Scholar
  36. 36.
    DePuy CH, Gronert S, Mullin A, Bierbaum VM (1990) Gas-phase SN2 and E2 reactions of alkyl halides. J Am Chem Soc 112:8650–8655. CrossRefGoogle Scholar
  37. 37.
    Carrascosa E, Meyer J, Zhang J et al (2017) Imaging dynamic fingerprints of competing E2 and SN2 reactions. Nat Commun 8:25. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Smith M (2013) March’s advanced organic chemistry : reactions, mechanisms, and structure., 7th Editio. WileyGoogle Scholar
  39. 39.
    Mikosch J, Trippel S, Eichhorn C et al (2008) Imaging nucleophilic substitution dynamics. Science (New York, NY) 319:183–186. CrossRefGoogle Scholar
  40. 40.
    Szabó I, Czakó G (2015) Revealing a double-inversion mechanism for the F<suP>−</suP> + CH3Cl SN2 reaction. Nat Commun 6:5972. CrossRefPubMedGoogle Scholar
  41. 41.
    Hamlin TA, Swart M, Bickelhaupt FM (2018) Nucleophilic substitution (SN2): dependence on nucleophile, leaving group, central atom, substituents, and solvent. ChemPhysChem 19:1315–1330. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Conner KM, Gronert S (2013) Impact of alkyl substituents on the gas-phase competition between substitution and elimination. J Organomet Chem 78:8606–8613. CrossRefGoogle Scholar
  43. 43.
    Piccini G, McCarty J, Valsson O, Parrinell M (2017) Variational flooding study of a S2 reaction. J Phys Chem A 8:580–583. CrossRefGoogle Scholar
  44. 44.
    Wang Y, Song H, Szabó I et al (2016) Mode-specific SN2 reaction dynamics. J Phys Chem Lett 7:3322–3327. CrossRefPubMedGoogle Scholar
  45. 45.
    Ma Y-T, Ma X, Li A et al (2017) Potential energy surface stationary points and dynamics of the F + CH3I double inversion mechanism. Phys Chem Chem Phys 19:20127–20136. CrossRefPubMedGoogle Scholar
  46. 46.
    Carrascosa E, Meyer J, Wester R (2017) Imaging the dynamics of ion–molecule reactions. Chem Soc Rev 46:7498–7516. CrossRefPubMedGoogle Scholar
  47. 47.
    Yang L, Zhang J, Xie J et al (2017) Competing E2 and SN2 mechanisms for the F + CH3CH2I reaction. J Phys Chem A 121:1078–1085. CrossRefPubMedGoogle Scholar
  48. 48.
    Carrascosa E, Meyer J, Michaelsen T et al (2018) Conservation of direct dynamics in sterically hindered SN2/E2 reactions. Chem Sci 9:693–701. CrossRefPubMedGoogle Scholar
  49. 49.
    Rablen PR, McLarney BD, Karlow BJ, Schneider JE (2014) How alkyl halide structure affects E2 and SN2 reaction barriers: E2 reactions are as sensitive as SN2 reactions. J Organomet Chem 79:867–879. CrossRefGoogle Scholar
  50. 50.
    Xie J, Ma X, Zhang J et al (2017) Effect of microsolvation on the OH (H2O)n + CH3I rate constant. Comparison of experiment and calculations for OH (H2O)2 + CH2I. Int J Mass Spectrom 418:122–129. CrossRefGoogle Scholar
  51. 51.
    Xie J, Kohale SC, Hase WL et al (2013) Temperature dependence of the OH + CH3I reaction kinetics. Experimental and simulation studies and atomic-level dynamics. J Phys Chem A 117:14019–14027. CrossRefPubMedGoogle Scholar
  52. 52.
    Frisch MJ, Trucks GW, Schlegel HB, et al Gaussian 09 Revision E.01Google Scholar
  53. 53.
    Carvalho-Silva VH, Aquilanti V, de Oliveira HCB, Mundim KC (2017) Deformed transition-state theory: deviation from Arrhenius behavior and application to bimolecular hydrogen transfer reaction rates in the tunneling regime. J Comput Chem 38:178–188. CrossRefPubMedGoogle Scholar
  54. 54.
    Aquilanti V, Coutinho ND, Carvalho-Silva VH (2017) Kinetics of low-temperature transitions and reaction rate theory from non-equilibrium distributions. Philos Trans R Soc Lond A 375Google Scholar
  55. 55.
    Sanches-Neto FO, Coutinho ND, Silva V (2017) A novel assessment of the role of the methyl radical and water formation channel in the CH3OH + H reaction. Phys Chem Chem Phys 19:24467–24477. CrossRefPubMedGoogle Scholar
  56. 56.
    Coutinho ND, Sanches-Neto F, Carvalho-Silva V et al (2018) Kinetics of the OH + HCl ⟶H2O+Cl reaction: rate determining roles of stereodynamics and roaming, and of quantum tunnelling. J Comput Chem 39:2508–2516. CrossRefGoogle Scholar
  57. 57.
    Aquilanti V, Mundim KCKC, Elango M et al (2010) Temperature dependence of chemical and biophysical rate processes: phenomenological approach to deviations from Arrhenius law. Chem Phys Lett 498:209–213. CrossRefGoogle Scholar
  58. 58.
    Valter H. Carvalho-Silva, Nayara D. Coutinho, Vincenzo Aquilanti, (2019) Temperature Dependence of Rate Processes Beyond Arrhenius and Eyring: Activation and Transitivity. Frontiers in Chemistry 7Google Scholar
  59. 59.
    CPMDversion 4.1, CPMDversion 3.17.1 (2012) Copyright IBMGoogle Scholar
  60. 60.
    Perdew JP, Burke K, Ernzerhof M (1996) Generalized gradient approximation made simple. Phys Rev Lett 77:3865–3868. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Perdew JP, Burke K, Ernzerhof M (1997) Generalized gradient approximation made simple [Phys. Rev. Lett. 77, 3865 (1996)]. Phys Rev Lett 78:1396CrossRefGoogle Scholar
  62. 62.
    Vanderbilt D (1990) Soft self-consistent pseudopotentials in a generalized eigenvalue formalism. Phys Rev B 41:7892–7895. CrossRefGoogle Scholar
  63. 63.
    Martyna GJ, Klein ML, Tuckerman M (1992) Nose–Hoover chains: the canonical ensemble via continuous dynamics. J Chem Phys 97:2635–2643. CrossRefGoogle Scholar
  64. 64.
    Johnson III, Russell D (2013) Computational chemistry comparison and benchmark database. In: NIST standard reference database, 69Google Scholar
  65. 65.
    Coutinho ND, Silva VHC, de Oliveira HCB et al (2015) Stereodynamical origin of anti-Arrhenius kinetics: negative activation energy and roaming for a four-atom reaction. J Phys Chem Lett:1553–1558. CrossRefGoogle Scholar
  66. 66.
    Coutinho ND, Aquilanti V, Silva VHCC et al (2016) Stereodirectional origin of anti-Arrhenius kinetics for a tetraatomic hydrogen exchange reaction: born-Oppenheimer molecular dynamics for OH + HBr. J Phys Chem A 120:5408–5417. CrossRefPubMedGoogle Scholar
  67. 67.
    Coutinho ND, Carvalho-Silva VH, de Oliveira HCB, Aquilanti V (2017) The HI + OH → H2O + I reaction by first-principles molecular dynamics: stereodirectional and anti-Arrhenius kineticsGoogle Scholar
  68. 68.
    Santin LG, Toledo EM, Carvalho-Silva VH et al (2016) Methanol solvation effect on the proton rearrangement of curcumin’s enol forms: an ab initio molecular dynamics and electronic structure viewpoint. J Phys Chem C 120:19923–19931CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Grupo de Química Teórica e Estrutural de Anápolis, Campus de Ciências Exatas e TecnológicasUniversidade Estadual de GoiásAnápolisBrazil
  2. 2.Dipartimento di Chimica, Biologia e BiotecnologieUniversità di PerugiaPerugiaItaly

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