Expanding the toolbox for supramolecular chemistry: probing host-guest interactions and binding with in situ FTIR...

Association constant (K _a) measurements provide fundamental information on host-guest interactions in supramolecular chemistry and other areas of science. Here we report the use of in situ FTIR spectroscopy to measure the K _a values across three classes of host-guest complexes that involve hydrogen bonding and halogen bonding. This approach can be performed with minimal sample preparation, does not require deuterated solvents, can measure association 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 conformations that are not in the ideal binding conformation until treatment with a suitable guest. These changes would not be observable by standard time-averaged NMR titration 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 K _a 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 broad areas of science.