Induced chiroptical changes of a water-soluble cryptophane by encapsulation of guest molecules and counterion effects

We report the synthesis of the water-soluble cryptophanol derivative 1 and the study of the chiroptical properties of its two enantiomers (>99 % ee) by polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD). We show that cryptophanol 1 exhibits unusual chiroptical properties in water under basic conditions (pH>12). For instance, the shapes of the ECD and VCD spectra of 1 in water were strongly dependent on the nature of the alkali metal ions (Li(+), Na(+), K(+), Cs(+)) surrounding the cryptophane and whether or not a guest molecule is present inside the cavity of the host. To the best of our knowledge, this is the first example in which the nature of these counterions governs the chiroptical properties of a host molecule. Moreover, specific ECD spectra were obtained depending on the size of the guest molecules. This makes 1 a good sensor for small neutral molecules in aqueous solvent. Finally, VCD experiments associated with DFT calculations show that the chiroptical changes can be directly correlated to the presence of charges close to the aromatic rings and with a conformational change of the alkyl chains upon encapsulation.