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


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.

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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.

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Rezende, M.V.C.S., Coutinho, N.D., Palazzetti, F. et al. Nucleophilic substitution vs elimination reaction of bisulfide ions with substituted methanes: exploration of chiral selectivity by stereodirectional first-principles dynamics and transition state theory. J Mol Model 25, 227 (2019).

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  • DFT
  • d-TST
  • Chiral discrimination
  • BOMD