Probing the hydrogen bonding of guest functional groups with [2.2.2]-cryptand/KF host <i>vs.</i> with solvent by ¹⁹F-NMR spectroscopy

We present a method for probing the local environment surrounding ammonium, hydroxyl, and carboxyl functional groups in solution by analyzing the ¹⁹F-NMR chemical shifts of [2.2.2]-cryptand ([2.2.2])/KF/protonated amino acid (AAH⁺) complexes. Specifically, we examine two competing structural features-solvation of guest functional groups <i>versus</i> complexation with the host-by monitoring hydrogen bonding interactions in deuterated ethylene glycol (EG-<i>d</i> ₆) and deuterated acetonitrile (CD₃CN). Model systems including [2.2.2]/KF/NH₄ ⁺Cl^-, [2.2.2]/KF/choline⁺Cl^- ([2.2.2]/KF/Ch⁺Cl^-), and 24-crown-8/CsF/betaine/H⁺Cl^- were employed to benchmark the chemical shift signatures associated with specific hydrogen bonding motifs. Based on the observed ¹⁹F NMR peaks, we assign the structures of [2.2/2]/AAH⁺ (AA = proline (Pro), threonine (Thr)) complexes in each solvent. In EG-<i>d</i> ₆, both complexes exhibit [-NH₃ ⁺⋯F^-] hydrogen bonding, while the carboxyl group in ProH⁺ and the carboxyl and hydroxyl groups in ThrH⁺ remain solvated and unbound to the host. In contrast, in CD₃CN, the carboxyl group in ProH⁺ and both the carboxyl and ammonium groups in ThrH⁺ directly engage in hydrogen bonding with F^-. These findings support the use of ¹⁹F-NMR spectroscopy as a sensitive probe of the [2.2.2]/KF/protonated amino acid system in solution and provide insight into potential structural correlations between solution-phase and gas-phase complexes.