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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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).
The authors declare no competing financial interests.
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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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