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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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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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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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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DOI: https://doi.org/10.1038/nchem.1618
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