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Chemistry inside molecular containers in the gas phase

Nature Chemistry volume 5, pages 376–382 (2013)Cite this article

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Abstract

Inner-phase chemical reactions of guest molecules encapsulated in a macromolecular cavity give fundamental insight into the relative stabilization of transition states by the surrounding walls of the host, thereby modelling the situation of substrates in enzymatic binding pockets. Although in solution several examples of inner-phase reactions are known, the use of cucurbiturils as macrocyclic hosts and bicyclic azoalkanes as guests has now enabled a systematic mass spectrometric investigation of inner-phase reactions in the gas phase, where typically the supply of thermal energy results in dissociation of the supramolecular host–guest assembly. The results reveal a sensitive interplay in which attractive and repulsive van der Waals interactions between the differently sized hosts and guests need to be balanced with a constrictive binding to allow thermally activated chemical reactions to compete with dissociation. The results are important for the understanding of supramolecular reactivity and have implications for catalysis.

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Figure 1
Figure 2: Reaction and dissociation pathways of the inclusion complexes of the bicyclic azoalkanes 1–3 with CBn (n = 6–8) in CID experiments.
Figure 3: Geometry-optimized molecular structures (HF/6-31G* level of theory) of [CB7 · 2 · H]+ complexes.
Figure 4: Ion mobilograms.
Figure 5: Model potentials for the interaction of a spherical guest positioned centrosymmetrically inside a host cavity versus guest volume.

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Acknowledgements

A.I.L., W.M.N. and K.I.A. thank the Deutsche Forschungsgemeinschaft (DFG, grant number NA-686/5), the Deutsche Akademische Austauschdienst (DAAD) and the Center for Functional Materials and Nanomolecular Science (NanoFun) for financial support, including graduate fellowships for A.I.L. and K.I.A. The Academy of Finland is acknowledged by E.K. for financial support (project number 127941). The FT-ICR facility is supported by Biocenter Finland. The authors thank L. Isaacs for making a reference sample of inverted CB7 available, M. Olivucci for donating computing time and D. V. Dearden for helpful comments on the results.

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Authors and Affiliations

  1. Department of Chemistry, Melville Laboratory for Polymer Synthesis, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    Tung-Chun Lee & Oren A. Scherman

  2. Department of Chemistry, University of Jyväskylä, Survontie 9, Jyväskylä, 40500, Finland

    Elina Kalenius

  3. School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, Bremen, D-28759, Germany

    Alexandra I. Lazar, Khaleel I. Assaf, Nikolai Kuhnert & Werner M. Nau

  4. Unilever R&D Vlaardingen, Olivier van Noortlaan 120, Vlaardingen, 3133 AT, The Netherlands

    Christian H. Grün

  5. Department of Chemistry, University of Eastern Finland, Joensuu Campus, Yliopistokatu 7, Joensuu, 80100, Finland

    Janne Jänis

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Contributions

T-C.L. initiated this project with E.K., O.A.S. and W.M.N. The manuscript was co-written by T-C.L., A.I.L. and W.M.N. and commented on by all the authors. All mass spectrometry experiments were conducted by E.K. and A.I.L. in the laboratories of J.J. and N.K., and C.H.G. conducted the ion-mobility experiments. K.I.A. performed the quantum-chemical and cross-section calculations. W.M.N. and A.I.L. analysed the data in terms of the model potentials. The student authors T-C.L. and A.I.L. contributed equally.

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Correspondence to Elina Kalenius or Werner M. Nau.

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Lee, TC., Kalenius, E., Lazar, A. et al. Chemistry inside molecular containers in the gas phase. Nature Chem 5, 376–382 (2013). https://doi.org/10.1038/nchem.1618

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