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Secret partner exchange made visible

Dynamics in a molecular host/guest relationship

PTB-News 3.2015
Especially interesting for


medical imaging

contrast agents

Atomic xenon can be temporarily encapsulated in molecular cages. Scientists from PTB have discovered that the direct exchange of xenon guest atoms — without the usual transition via a temporarily emptied host molecule — plays an important role here. This process could be used in new biomedical analysis and imaging procedures.

Basic and degenerated exchange process

The cage molecule cryptophane A (CrA) has been known for some time for its ability to bind individual xenon molecules reversibly. The inclusion compound has been used in recent developments in bioanalytics and in molecular imaging to make biomarkers or tissue (e.g. tumors) visible. The required specificity is attained by functionalizing the CrA, for example by linking it with a specific antibody or ligand. This CrA/antibody (or ligand) conjugate represents a biosensor whose location, quantity and state can be determined by applying nuclear magnetic resonance spectroscopy and imaging to the bound xenon molecules. To obtain high sensitivity, it is hereby extremely important to generate excess (by several orders of magnitude) magnetization for the 129Xe isotope and to accumulate, over a longer period of time, signals that are attributed to the biosensor. All this leads to very low limits of detection in the range of picomoles – which is an important precondition to be able to investigate biomolecular processes in native systems in situ.

The basic interaction between xenon and CrA resides in the occupying or leaving of an – otherwise – empty cage molecule. Furthermore, even in an already occupied cage molecule, the xenon molecule could still be supplanted by another, formerly free one – i.e. a direct change in occupancy could take place. This exchange process would be degenerated, since the initial state and the final state could not be differentiated, so that the change would remain undetected — contrary to the basic interaction. To make degenerate exchange processes visible, scientists from PTB have used a trick: by varying the xenon concentration, they could detect a modulation of the frequency of xenon replacements in CrA which is solely characteristic of degenerate exchange. In an aqueous environment – such as that prevailing in living organisms – degenerate exchange can even become the dominant mode in the host/guest interaction. The findings are of great importance for the measurement sensitivity and for quantitative analyses in the new approaches using the CrA/xenon host/guest system and are currently being investigated as to their potential for biomedical applications.


Lorenz Mitschang
Department 8.1 Medical Metrology
Phone: +49 (0)30 3481-7632
E-mail: lorenz.mitschang(at)ptb.de


Scientific publication

S. Korchak, W. Kilian, L. Mitschang: Degeneracy in cryptophane-xenon complex formation in aqueous solution. Chem. Comm. 51, 1721 (2015)