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Real-time monitoring of reaction stereochemistry through single-molecule observations of chirality-induced spin selectivity

Nature Chemistry volume 15, pages 972–979 (2023)Cite this article

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Abstract

Stereochemistry has an essential role in organic synthesis, biological catalysis and physical processes. In situ chirality identification and asymmetric synthesis are non-trivial tasks, especially for single-molecule systems. However, going beyond the chiral characterization of a large number of molecules (which inevitably leads to ensemble averaging) is crucial for elucidating the different properties induced by the chiral nature of the molecules. Here we report direct monitoring of chirality variations during a Michael addition followed by proton transfer and keto–enol tautomerism in a single molecule. Taking advantage of the chirality-induced spin selectivity effect, continuous current measurements through a single-molecule junction revealed in situ chirality variations during the reaction. Chirality identification at a high sensitivity level provides a promising tool for the study of symmetry-breaking reactions and sheds light on the origin of the chirality-induced spin selectivity effect itself.

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Fig. 1: Monitoring of the Michael reaction in a molecular junction setup.
Fig. 2: Complete description of the Michael addition on a routine Au/Cr/graphene/single molecule/graphene/Cr/Au device.
Fig. 3: Single-molecule spin filtering and the CISS effect.
Fig. 4: Real-time monitoring of chirality variations during the reaction.

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Additional discussions and data supporting this article are available in the Supplementary Information. Source data are provided with this paper.

References

  1. Dalko, P. I. & Moisan, L. In the golden age of organocatalysis. Angew. Chem. Int. Ed. 43, 5138–5175 (2004).

    Article  CAS  Google Scholar 

  2. Bornscheuer, U. T. et al. Engineering the third wave of biocatalysis. Nature 485, 185–194 (2012).

    Article  CAS  PubMed  Google Scholar 

  3. Hsieh, D. et al. Observation of unconventional quantum spin textures in topological insulators. Science 323, 919–922 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Hendry, E. et al. Ultrasensitive detection and characterization of biomolecules using superchiral fields. Nat. Nanotechnol. 5, 783–787 (2010).

    Article  CAS  PubMed  Google Scholar 

  5. Tu, H.-F., Yang, P., Lin, Z.-H., Zheng, C. & You, S.-L. Time-dependent enantiodivergent synthesis via sequential kinetic resolution. Nat. Chem. 12, 838–844 (2020).

    Article  CAS  PubMed  Google Scholar 

  6. Yeom, J. et al. Chiromagnetic nanoparticles and gels. Science 359, 309–314 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Tang, Y. & Cohen Adam, E. Enhanced enantioselectivity in excitation of chiral molecules by superchiral light. Science 332, 333–336 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Banerjee-Ghosh, K. et al. Separation of enantiomers by their enantiospecific interaction with achiral magnetic substrates. Science 360, 1331–1334 (2018).

    Article  CAS  PubMed  Google Scholar 

  9. Kumar, J. et al. Detection of amyloid fibrils in Parkinson’s disease using plasmonic chirality. Proc. Natl Acad. Sci. USA 115, 3225–3230 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Steendam, R. R. E. et al. Emergence of single-molecular chirality from achiral reactants. Nat. Commun. 5, 5543 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Gohler, B. et al. Spin selectivity in electron transmission through self-assembled monolayers of double-stranded DNA. Science 331, 894–897 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Naaman, R., Paltiel, Y. & Waldeck, D. H. Chiral molecules and the electron spin. Nat. Rev. Chem. 3, 250–260 (2019).

    Article  CAS  Google Scholar 

  13. Kim, Y. H. et al. Chiral-induced spin selectivity enables a room-temperature spin light-emitting diode. Science 371, 1129–1133 (2021).

    Article  CAS  PubMed  Google Scholar 

  14. Naaman, R., Paltiel, Y. & Waldeck, D. H. Chiral molecules and the spin selectivity effect. J. Phys. Chem. Lett. 11, 3660–3666 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aragones, A. C. et al. Measuring the spin-polarization power of a single chiral molecule. Small 13, 1602519 (2017).

    Article  Google Scholar 

  16. Naaman, R. & Waldeck, D. H. Spintronics and chirality: spin selectivity in electron transport through chiral molecules. Annu. Rev. Phys. Chem. 66, 263–281 (2015).

    Article  CAS  PubMed  Google Scholar 

  17. Al-Bustami, H. et al. Single nanoparticle magnetic spin memristor. Small 14, 1801249 (2018).

    Article  Google Scholar 

  18. Brandt, J. R., Salerno, F. & Fuchter, M. J. The added value of small-molecule chirality in technological applications. Nat. Rev. Chem. 1, 0045 (2017).

    Article  CAS  Google Scholar 

  19. Michaeli, K., Kantor-Uriel, N., Naaman, R. & Waldeck, D. H. The electron’s spin and molecular chirality—how are they related and how do they affect life processes? Chem. Soc. Rev. 45, 6478–6487 (2016).

    Article  CAS  PubMed  Google Scholar 

  20. Alwan, S. & Dubi, Y. Spinterface origin for the chirality-induced spin-selectivity effect. J. Am. Chem. Soc. 143, 14235–14241 (2021).

    Article  CAS  PubMed  Google Scholar 

  21. Ghazaryan, A., Paltiel, Y. & Lemeshko, M. Analytic model of chiral-induced spin selectivity. J. Phys. Chem. C 124, 11716–11721 (2020).

    Article  CAS  Google Scholar 

  22. Qi, D., Kenaan, A., Cui, D. & Song, J. Novel insights into the selection to electron’s spin of chiral structure. Nano Energy 52, 142–152 (2018).

    Article  CAS  Google Scholar 

  23. Dubi, Y. Spinterface chirality-induced spin selectivity effect in bio-molecules. Chem. Sci. 13, 10878–10883 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Evers, F., Korytár, R., Tewari, S. & van Ruitenbeek, J. M. Advances and challenges in single-molecule electron transport. Rev. Mod. Phys. 92, 035001 (2020).

    Article  CAS  Google Scholar 

  25. Xin, N. et al. Concepts in the design and engineering of single-molecule electronic devices. Nat. Rev. Phys. 1, 211–230 (2019).

    Article  Google Scholar 

  26. Park, J. et al. Coulomb blockade and the Kondo effect in single-atom transistors. Nature 417, 722–725 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Bai, J. et al. Anti-resonance features of destructive quantum interference in single-molecule thiophene junctions achieved by electrochemical gating. Nat. Mater. 18, 364–369 (2019).

    Article  CAS  PubMed  Google Scholar 

  28. Winkelmann, C. B., Roch, N., Wernsdorfer, W., Bouchiat, V. & Balestro, F. Superconductivity in a single-C60 transistor. Nat. Phys. 5, 876–879 (2009).

    Article  CAS  Google Scholar 

  29. Kim, W. Y. & Kim, K. S. Tuning molecular orbitals in molecular electronics and spintronics. Acc. Chem. Res. 43, 111–120 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Waldrop, M. M. The chips are down for Moore’s law. Nat. News 530, 144–147 (2016).

    Article  CAS  Google Scholar 

  31. Li, Y., Yang, C. & Guo, X. Single-molecule electrical detection: a promising route toward the fundamental limits of chemistry and life science. Acc. Chem. Res. 53, 159–169 (2020).

    Article  CAS  PubMed  Google Scholar 

  32. Yang, C. et al. Single-molecule electrical spectroscopy of organocatalysis. Matter 4, 2874–2885 (2021).

    Article  CAS  Google Scholar 

  33. Yang, C. et al. Unveiling the full reaction path of the Suzuki–Miyaura cross-coupling in a single-molecule junction. Nat. Nanotechnol. 16, 1214–1223 (2021).

    Article  CAS  PubMed  Google Scholar 

  34. Chen, H. et al. Electron-catalyzed dehydrogenation in a single-molecule junction. J. Am. Chem. Soc. 143, 8476–8487 (2021).

    Article  CAS  PubMed  Google Scholar 

  35. Aragones, A. C. et al. Electrostatic catalysis of a Diels–Alder reaction. Nature 531, 88–91 (2016).

    Article  CAS  PubMed  Google Scholar 

  36. Huang, G. & Li, X. Applications of Michael addition reaction in organic synthesis. Curr. Org. Synth. 14, 568–571 (2017).

    Article  CAS  Google Scholar 

  37. Sibi, P. M. & Manyem, S. Enantioselective conjugate additions. Tetrahedron 56, 8033–8061 (2000).

    Article  CAS  Google Scholar 

  38. Yang, C. et al. Electric field–catalyzed single-molecule Diels–Alder reaction dynamics. Sci. Adv. 7, eabf0689 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gómez-Torres, E., Alonso, D. A., Gómez-Bengoa, E. & Nájera, C. Enantioselective synthesis of succinimides by Michael addition of 1,3-dicarbonyl compounds to maleimides catalyzed by a chiral bis(2-aminobenzimidazole) organocatalyst. Eur. J. Org. Chem. 2013, 1434–1440 (2013).

    Article  Google Scholar 

  40. Gersten, J., Kaasbjerg, K. & Nitzan, A. Induced spin filtering in electron transmission through chiral molecular layers adsorbed on metals with strong spin–orbit coupling. J. Chem. Phys. 139, 114111 (2013).

    Article  PubMed  Google Scholar 

  41. Xie, Z. et al. Spin specific electron conduction through DNA oligomers. Nano Lett. 11, 4652–4655 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Kondou, K. et al. Chirality-induced magnetoresistance due to thermally driven spin polarization. J. Am. Chem. Soc. 144, 7302–7307 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Das, T. K., Tassinari, F., Naaman, R. & Fransson, J. Temperature-dependent chiral-induced spin selectivity effect: experiments and theory. J. Phys. Chem. C 126, 3257–3264 (2022).

    Article  CAS  Google Scholar 

  44. Jeong, H., Li, H. B., Domulevicz, L. & Hihath, J. An on-chip break junction system for combined single-molecule conductance and Raman spectroscopies. Adv. Funct. Mater. 30, 2000615 (2020).

    Article  CAS  Google Scholar 

  45. Badala Viswanatha, C. et al. Vectorial electron spin filtering by an all-chiral metal–molecule heterostructure. J. Phys. Chem. Lett. 13, 6244–6249 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We acknowledge primary financial support from the National Key R&D Program of China (2022YFE0128700, 2017YFA0204901 and 2021YFA1200101), National Natural Science Foundation of China (22150013, 22173050, 21727806 and 21933001), Tencent Foundation (through the Xplorer Prize), Natural Science Foundation of Beijing (2222009) and Frontiers Science Center for New Organic Matter at Nankai University (63181206). Y.D. acknowledges support from the Israel Science Foundation (1360/17). S.Z. and Z.L. appreciate support from the High-Performance Computing Platform of the Center for Life Science (Peking University) and High-Performance Computing Platform of Peking University.

Author information

Author notes

  1. These authors contributed equally: Chen Yang, Yanwei Li.

Authors and Affiliations

  1. Beijing National Laboratory for Molecular Sciences, National Biomedical Imaging Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, People’s Republic of China

    Chen Yang, Shuyao Zhou, Yilin Guo, Zhirong Liu & Xuefeng Guo

  2. Environment Research Institute, Shandong University, Qingdao, People’s Republic of China

    Yanwei Li

  3. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA

    Yanwei Li & Kendall N. Houk

  4. Center of Single-Molecule Sciences, Institute of Modern Optics, Frontiers Science Center for New Organic Matter, College of Electronic Information and Optical Engineering, Nankai University, Tianjin, People’s Republic of China

    Chuancheng Jia & Xuefeng Guo

  5. Department of Chemistry, Ben-Gurion University of the Negev, Be’er-Sheva, Israel

    Yonatan Dubi

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Contributions

X.G., Y.D. and K.N.H. conceived of and designed the experiments. C.Y., Y.G. and C.J. fabricated the devices and performed the device measurements. Y.D., Y.L., S.Z. and Z.L. built and analysed the theoretical model and performed the quantum transport calculation. X.G., Y.D., K.N.H. and C.Y. analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Kendall N. Houk, Yonatan Dubi or Xuefeng Guo.

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Nature Chemistry thanks Ismael Diez Perez, Kun Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods and Figs. 1–49.

Source data

Source Data Fig. 2

I−t curves, corresponding histogram and potential energy surface and statistical source data.

Source Data Fig. 3

Experimental and simulated I–V curves and CISS polarization.

Source Data Fig. 4

I–t curves, corresponding histogram and potential energy surface.

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Yang, C., Li, Y., Zhou, S. et al. Real-time monitoring of reaction stereochemistry through single-molecule observations of chirality-induced spin selectivity. Nat. Chem. 15, 972–979 (2023). https://doi.org/10.1038/s41557-023-01212-2

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