Probing the hydrogen bonding of guest functional groups with [2.2.2]-cryptand/KF host vs. 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 versus complexation with the host-by monitoring hydrogen bonding interactions in deuterated ethylene glycol (EG-d 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-d 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.