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Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

Nature Chemistry volume 9, pages 164–170 (2017)Cite this article

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Abstract

The reduction of disulfides has a broad importance in chemistry, biochemistry and materials science, particularly those methods that use mechanochemical activation. Here we show, using isotensional simulations, that strikingly different mechanisms govern disulfide cleavage depending on the external force. Desolvation and resolvation processes are found to be crucial, as they have a direct impact on activation free energies. The preferred pathway at moderate forces, a bimolecular SN2 attack of OH– at sulfur, competes with unimolecular C–S bond rupture at about 2 nN, and the latter even becomes barrierless at greater applied forces. Moreover, our study unveils a surprisingly rich reactivity scenario that also includes the transformation of concerted SN2 reactions into pure bond-breaking processes at specific forces. Given that these forces are easily reached in experiments, these insights will fundamentally change our understanding of mechanochemical activation in general, which is now expected to be considerably more intricate than previously thought.

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Figure 1: Force dependence of the computed activation free energy, , for all five depicted reaction pathways.
Figure 2: Solvation of the OH− nucleophile by water studied as a function of external force using the rigorous all-QM AIMD approach and a QM/MM hybrid MD approximation.
Figure 3: Change of the reaction mechanism from a concerted one-step reaction to a two-step process for the OH− attack at an α-carbon.
Figure 4: Change of the α-elimination reaction mechanism with applied force.

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Acknowledgements

We are grateful to Deutsche Forschungsgemeinsschaft (Reinhart Koselleck Grant ‘Understanding Mechanochemistry’ MA 1547/9 and Cluster of Excellence ‘RESOLV’ EXC 1069), Alexander von Humboldt Stiftung (Humboldt Fellowships to J.R.A), Spanish Government (Ramón y Cajal Fellowship to J.R.A.), National Science Center Poland under Grant No. 2014/13/B/ST4/05009 and Ministry of Science and Higher Education Poland under Grant No. 627/STYP/9/20l4 (Fellowships to P.D.) for partial financial support. The authors acknowledge the Gauss Centre for Supercomputing (GCS) for providing computing time for a GCS Large Scale Project on JUQUEEN at the Jülich Supercomputing Centre as well as additional computational support by BOVILAB@RUB, HPC–RESOLV, Rechnerverbund–NRW, Wrocław Supercomputer Center, Galera–ACTION Cluster and Academic Computer Center in Gdańsk (CI TASK).

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  1. Przemyslaw Dopieralski, Jordi Ribas–Arino, Padmesh Anjukandi & Martin Krupicka

    Present address: Present address: Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland (P.D.); Departament de Química Física and IQTCUB, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain (J.R.-A.); Department of Chemistry, Indian Institute of Technology Palakkad, Ahalia Integrated Campus, Kozhippara PO. 678557, Kerala, India (P.A.). Max-Planck-Institut für Chemische Energiekonversion, Stiftstr. 34–36, 45470 Mülheim an der Ruhr, Germany (M.K.),

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  1. Lehrstuhl für Theoretische Chemie, Ruhr–Universität Bochum, Bochum, 44780, Germany

    Przemyslaw Dopieralski, Jordi Ribas–Arino, Padmesh Anjukandi, Martin Krupicka & Dominik Marx

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  1. Przemyslaw Dopieralski
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P.D., J.R.-A. and D.M. conceived and designed the research; P.D. performed the calculations; P.D., J.R.-A., P.A., M.K. and D.M. analysed the data; P.D., J.R.-A. and D.M. co-wrote the paper.

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Correspondence to Przemyslaw Dopieralski or Jordi Ribas–Arino.

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Dopieralski, P., Ribas–Arino, J., Anjukandi, P. et al. Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution. Nature Chem 9, 164–170 (2017). https://doi.org/10.1038/nchem.2632

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