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Experimental evidence for the functional relevance of anion–π interactions

Nature Chemistry volume 2, pages 533–538 (2010)Cite this article

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Abstract

Attractive in theory and confirmed to exist, anion–π interactions have never really been seen at work. To catch them in action, we prepared a collection of monomeric, cyclic and rod-shaped naphthalenediimide transporters. Their ability to exert anion–π interactions was demonstrated by electrospray tandem mass spectrometry in combination with theoretical calculations. To relate this structural evidence to transport activity in bilayer membranes, affinity and selectivity sequences were recorded. π-acidification and active-site decrowding increased binding, transport and chloride > bromide > iodide selectivity, and supramolecular organization inverted acetate > nitrate to nitrate > acetate selectivity. We conclude that anion–π interactions on monomeric surfaces are ideal for chloride recognition, whereas their supramolecular enhancement by π,π-interactions appears perfect to target nitrate. Chloride transporters are relevant to treat channelopathies, and nitrate sensors to monitor cellular signaling and cardiovascular diseases. A big impact on organocatalysis can be expected from the stabilization of anionic transition states on chiral π-acidic surfaces.

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Figure 1: Structures and hypothesized active suprastructures of anion–π transporters.
Figure 2: Synthesis of dicyano NDIs.
Figure 3: Laser-induced ESI-MS-MS fragmentation of heterodimer complexes and charge-transfer absorption.
Figure 4: Molecular modelling of anion–π interactions.
Figure 5: Transport selectivity.

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Acknowledgements

We thank D.-H. Tran, J. Praz and L. Maffiolo for contributions to synthesis, D. Jeannerat, A. Pinto and S. Grass for NMR measurements, P. Perrottet, N. Oudry and G. Hopfgartner for mass spectrometry, the Swiss National Supercomputing Center in Manno for CPU time, and the University of Geneva (S.M., J.M.), the University of Basel (M.M.), the Deutsche Forschungsgemeinschaft (C.A.S.), the Fonds der Chemischen Industrie (C.A.S.), the NCCR Nanoscale Sciences of the SNF (S.G., M.M.) and the Swiss NSF (S.M., M.M.) for financial support.

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  1. Ryan E. Dawson and Andreas Hennig: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Organic Chemistry, University of Geneva, Geneva, Switzerland

    Ryan E. Dawson, Andreas Hennig, Daniel Emery, Velayutham Ravikumar, Javier Montenegro, Toshihide Takeuchi, Jiri Mareda & Stefan Matile

  2. Institut für Chemie und Biochemie der Freien Universität, Berlin, Germany

    Dominik P. Weimann & Christoph A. Schalley

  3. Department of Chemistry, University of Basel, Basel, Switzerland

    Sandro Gabutti & Marcel Mayor

  4. Institute of Nanotechnology, Karlsruhe Institute of Technology, Germany

    Marcel Mayor

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Contributions

R.E.D., V.R., J.M., T.T., S.G. and A.H. synthesized compounds, A.H. and R.E.D. transported ions across membranes, D.P.W. performed the (tandem) mass spectrometric experiments and evaluated the mass spectrometry data, D.E. prepared computational models, M.M., J.M., C.A.S. and S.M. directed the study, contributing to design, execution and interpretation of experiments, computer modelling and manuscript writing.

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Correspondence to Stefan Matile.

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Dawson, R., Hennig, A., Weimann, D. et al. Experimental evidence for the functional relevance of anion–π interactions. Nature Chem 2, 533–538 (2010). https://doi.org/10.1038/nchem.657

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