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Exploiting non-covalent π interactions for catalyst design

Abstract

Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.

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Figure 1: Overview of catalysis and non-covalent π interactions.
Figure 2: Overview of π-stacking geometries and evidence for the direct interaction model.
Figure 3: Experiments quantifying effects on π-stacking interactions.
Figure 4: Studies of XH–π interactions.
Figure 5: Examples of cation–π interactions.
Figure 6: Examples of anion–π interactions.
Figure 7: Substituent effects on anion–π interactions.
Figure 8: Examples of lone pair–π interactions.

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Acknowledgements

We thank A. Milo for discussions. M.J.H. and M.S.S. thank the NSF (CHE-1361296) for financial support; A.J.N. and F.D.T. thank the NIHGMS (R35 GM118190) for financial support.

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Neel, A., Hilton, M., Sigman, M. et al. Exploiting non-covalent π interactions for catalyst design. Nature 543, 637–646 (2017). https://doi.org/10.1038/nature21701

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