Preferential Binding to a Mannoside of a Pyridine–Acetylene–Phenol Macrocycle with a Fluorine Substituent in the Cavity

We developed a pyridine–acetylene–phenol macrocycle in which a fluorine atom was introduced in place of a hydroxy group, as a host for the selective binding to epimers of glucose. The fluorine atom was expected to work as a negatively charged infill repelling oxygen atoms of saccharides and prevent the efficient formation of a hydrogen-bond network with a glucoside, whose cross-section size is larger than those of the corresponding epimers, especially of a mannoside. UV–Vis and fluorescence titration experiments revealed that this host showed a higher affinity for a mannoside than a glucoside. ¹H NMR and molecular modeling suggested that the fluorine atom acts as a moderate infill weakening the binding to a glucoside. This result indicates that selectivity for guest molecules can be modified by replacing a hydroxy group and a hydrogen atom in host molecules with a fluorine atom.