Expanding the Toolbox for Supramolecular Chemistry: Probing Host-Guest Interactions with in situ FTIR Spectroscopy for Struc-tural and Dynamic Insights

Association constant (Ka) measurements provide fundamental information on host-guest interactions in supramolecular chemistry and other areas of science. Many techniques can be used to measure Ka values, with NMR spectroscopy often providing useful information on time-averaged interactions or changes in geometry due to perturbations in chemical shifts. Here we report the use of in situ FTIR spectroscopy to measure the Ka values of supramolecular host-guest complexes across three classes of host-guest complexes using different types of interactions including hydrogen bonding and halogen bonding. This approach can be performed with minimal sample preparation, does not require deuterated solvents, can measure asso-ciation based on changes in host or guest vibrations, and benefits from a much shorter timescale than NMR spectroscopy. Due to its fast timescale, FTIR spectroscopy also provides details on host/guest conformational changes, such as the presence of unsymmetrical host conformation that are not in the ideal binding conformation until treatment with a suitable guest, which would otherwise not be observed in more common time-averaged NMR measurements. Using this approach, we demonstrated the capabilities and challenges of this technique to investigate host-guest interactions of three anion receptors that use hydrogen or halogen bonding with both mono- and polyatomic anions. In addition to directly observing how host-guest interactions impact bonding within the individual molecules, we also demonstrate that global fitting of the FTIR spectra is an effective and robust approach to measure Ka values of these host-guest complexes. We anticipate that this method will provide a new and useful approach to investigating the dynamics and specific interactions across abroad areas of science.