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

Abstract

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-d₆) 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-d₆, 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.