Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Highly dynamic motion of crown ethers along oligolysine peptide chains

A Corrigendum to this article was published on 01 November 2009

This article has been updated


Molecular mobility has attracted considerable attention in supramolecular chemistry and biochemistry, but the simple question of whether a small molecule can move directly between different binding sites of a multitopic host without intermediate dissociation has not been addressed so far. To study such processes, we consider hydrogen/deuterium exchange experiments on a model system comprising complexes formed between 18-crown-6 and oligolysine peptides. Because direct binding-site hopping is indistinguishable in solution from a dissociation/reassociation mechanism, here we show that the high vacuum of a mass spectrometer offers a unique environment for probing such processes. The highly dynamic motion of crown ethers along oligolysine peptide chains proceeds mechanistically by a simultaneous transfer of the crown ether from its ammonium ion binding site to a nearby amino group together with a proton. Furthermore, the exchange experiments unambiguously reveal the zwitterionic structure of the 18-crown-6/oligolysine complexes, highlighting the versatility and potential of gas-phase experiments for investigating non-covalent interactions.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Schematic representation of crown ether movement along a Lys15 peptide.
Figure 2: Mechanistic alternatives of gas-phase H/D exchange reactions.
Figure 3: Gas-phase H/D-exchange experiments conducted with Lys15 and its crown ether complexes.
Figure 4: Control experiments unravel mechanistic details of the crown ether movement.
Figure 5: To be or not to be a zwitterion.

Change history

  • 23 October 2009

    At roughly the same time, the authors of this Article independently submitted a manuscript to Angewandte Chemie, in which the method presented here was applied to polyamino propylene amine dendrimers. The authors forgot to mention this publication and would like to apologize for their mistake. The missing reference is: Winkler, H. D. F., Weimann, D. P., Springer, A. and Schalley, C. A. Dynamic motion in crown ether dendrimer complexes: A "spacewalk" on the molecular scale. Angew. Chem. Int. Ed. 48, 7246-7250 (2009).


  1. Meot-Ner (Mautner), M. The ionic hydrogen bond. Chem. Rev. 105, 213–284 (2005).

    Article  Google Scholar 

  2. Lifshitz, C. A review of gas-phase H/D exchange experiments: the protonated arginine dimer and bradykinin nonapeptide systems. Int. J. Mass Spectrom. 234, 63–70 (2004).

    CAS  Article  Google Scholar 

  3. Kellersberger, K. A., Desjupa, C., Liang, Y. J., Pope, R. M. & Dearden, D. V. Gas phase studies of ammonium-cyclodextrin compounds using Fourier transform ion cyclotron resonance. Int. J. Mass Spectrom. 193, 181–195 (1999).

    CAS  Article  Google Scholar 

  4. Ventola, E., Rissanen, K. & Vainiotalo, P. Mass spectrometric investigation of noncovalent complexation between a tetratosylated resorcarene and alkyl ammonium ions. Chem. Eur. J. 10, 6152–6162 (2004).

    CAS  Article  Google Scholar 

  5. Ventola, E., Hyyryläinen, A. & Vainiotalo, P. Complex formation between a tetramesityl sulfonated resorcarene and alkylammonium ions: a mass spectrometric study of noncovalent interactions. Rapid Commun. Mass Spectrom. 20, 1218–1224 (2006).

    CAS  Article  Google Scholar 

  6. Kalenius, E., Moiani, D., Dalcanale, E. & Vainiotalo, P. Measuring H-bonding supramolecular complexes by gas phase ion-molecule reactions. Chem. Commun. 3865–3867 (2007).

  7. Wood, T. D. et al. Gas-phase folding and unfolding of cytochrome c cations. Prod. Natl Acad. Sci. USA 92, 2421–2454 (1995).

    Article  Google Scholar 

  8. Wyttenbach, T. & Bowers, M. T. Gas phase conformations of biological molecules: the hydrogen/deuterium exchange mechanism. J. Am. Soc. Mass Spectrom. 10, 9–14 (1999).

    CAS  Article  Google Scholar 

  9. Lee, S.-W., Lee, H.-N., Kim, H. S. & Beauchamp, J. L. Selective binding of crown ethers to protonated peptides can be used to probe mechanisms of H/D exchange and collision-induced dissociation reactions in the gas phase. J. Am. Chem. Soc. 120, 5800–5805 (1998).

    CAS  Article  Google Scholar 

  10. Lias, S. G. Thermoneutral isotope exchange-reactions in proton-bound complexes of water with organic-molecules — correlations with energetics of formation of the corresponding association ions. J. Phys. Chem. 88, 4401–4407 (1984).

    CAS  Article  Google Scholar 

  11. Cram, D. J. & Cram, J. M. Design of complexes between synthetic hosts and organic guests. Acc. Chem. Res. 11, 8–14 (1978).

    CAS  Article  Google Scholar 

  12. Rüdiger, V. et al. Crown ether-ammonium complexes: binding mechanisms and solvent effects. Eur. J. Org. Chem. 1847–1856 (1999).

  13. Maleknia, S. & Brodbelt, J. Cavity-size-dependent dissociation of crown ether/ammonium ion complexes in the gas phase. J. Am. Chem. Soc. 115, 2837–2843 (1993).

    CAS  Article  Google Scholar 

  14. Dearden, D. V., Liang, Y. J., Nicoll, J. B. & Kellersberger, K. A. Study of gas-phase molecular recognition using Fourier transform ion cyclotron resonance mass spectrometry (FTICR/MS). J. Mass Spectrom. 36, 989–997 (2001).

    CAS  Article  Google Scholar 

  15. Dearden, D. V., Desjupa, C., Liang, Y. J., Bradshaw, J. S. & Izatt, R. M. Intrinsic contributions to chiral recognition: Discrimination between enantiomeric amines by dimethyldiketopyridino-18-crown-6 in the gas phase. J. Am. Chem. Soc. 119, 353–359 (1997).

    CAS  Article  Google Scholar 

  16. Wu, H. F. & Brodbelt, J. S. Comparison of the orders of gas-phase basicities and ammonium ion affinities of polyethers by the kinetic method and ligand-exchange technique. J. Am. Soc. Mass Spectrom. 4, 718–722 (1993).

    CAS  Article  Google Scholar 

  17. Liou, C.-C. & Brodbelt, J. S. Comparison of gas-phase proton and ammonium ion affinities of crown ethers and related acyclic analogs. J. Am. Chem. Soc. 114, 6761–6764 (1992).

    CAS  Article  Google Scholar 

  18. Dearden, D. V. & Chu, I.-H. Relative ammonium ion affinities of 18-crown-6 and the isomers of dicyclohexano-18-crown-6. J. Incl. Phenomena Mol. Recogn. 29, 269–282 (1997).

    CAS  Article  Google Scholar 

  19. Julian, R. R. & Beauchamp, J. L. The unusually high proton affinity of aza-18-crown-6 ether: Implications for the molecular recognition of lysine in peptides by lariat crown ethers. J. Am. Soc. Mass. Spectrom. 13, 493–498 (2002).

    CAS  Article  Google Scholar 

  20. Julian, R. R., May, J. A., Stoltz, B. M. & Beauchamp, J. L. Biomimetic approaches to gas phase peptide chemistry: combining selective binding motifs with reactive carbene precursors to form molecular mousetraps. Int. J. Mass Spectrom. 228, 851–864 (2003).

    CAS  Article  Google Scholar 

  21. Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F. & Whitehouse, C. M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989).

    CAS  Article  Google Scholar 

  22. Marshall, A. G., Hendrickson, C. S. & Jackson, G. S. Fourier transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrom. Rev. 17, 1–35 (1998).

    CAS  Article  Google Scholar 

  23. Hofstadler, S. A., Sannes-Lowery, K. A. & Griffey, R. H. A gated-beam electrospray ionization source with an external ion reservoir. A new tool for the characterization of biomolecules using electrospray ionization mass spectrometry Rapid Commun. Mass. Spectrom. 13, 1971–1979 (1999).

    CAS  Google Scholar 

  24. Hofstadler, S. A., Sannes-Lowery, K. A. & Griffey, R. H. Enhanced gas-phase hydrogen-deuterium exchange of oligonucleotide and protein ions stored in an external multipole ion reservoir. J. Mass. Spectrom. 35, 62–70 (2000).

    CAS  Article  Google Scholar 

  25. Campbell, S., Rodgers, M. T., Marzluff, E. M. & Beauchamp, J. L. Deuterium exchange reactions as a probe of biomolecule structure. Fundamental studies of gas phase H/D exchange reactions of protonated glycine oligomers with D2O, CD3OD, CD3CO2D, and ND3 . J. Am. Chem. Soc. 117, 12840–12854 (1995).

    CAS  Article  Google Scholar 

  26. Cox, H. A., Julian, R. R., Lee, S. W. & Beauchamp, J. L. Gas-Phase H/D exchange of sodiated glycine oligomers with ND3: exchange kinetics do not reflect parent ion structures. J. Am. Chem. Soc. 126, 6485–6490 (2004).

    CAS  Article  Google Scholar 

  27. Freitas, M. A. & Marshall, A. G. Rate and extent of gas-phase hydrogen/deuterium exchange of bradykinins: evidence for peptide zwitterions in the gas phase. Int. J. Mass Spectrom. 182–183, 221–231 (1999).

    Article  Google Scholar 

  28. Polfer, N. C., Dunbar, R. C. & Oomens, J. Observation of zwitterion formation in the gas-phase H/D-exchange with CH3OD: solution-phase structures in the gas phase. J. Am. Soc. Mass Spectrom. 18, 512–516 (2007).

    CAS  Article  Google Scholar 

Download references


We thank Andreas Springer for valuable scientific advice and acknowledge funding from the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.

Author information

Authors and Affiliations



C.A.S., H.D.F.W. and D.P.W. conceived, designed and performed the mass spectrometric experiments and co-wrote the paper. J.A.F. and B.K. contributed the peptides. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Christoph A. Schalley.

Supplementary information

Supplementary information

Supplementary information (PDF 1540 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Weimann, D., Winkler, H., Falenski, J. et al. Highly dynamic motion of crown ethers along oligolysine peptide chains. Nature Chem 1, 573–577 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing