Induced Chiroptical Changes of a Water‐Soluble Cryptophane by Encapsulation of Guest Molecules and Counterion Effects

Abstract

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.

Effect of pH and Counterions on the Encapsulation Properties of Xenon in Water‐Soluble Cryptophanes

“…This region corresponds to the (O-CH 2 -CH 2 -O) linker protons and the axial proton of the CTV part. An assumption, which is consistent with the observations of Luhmer et al [24] and Bouchet et al [17] is that this slow exchange dealing with the ethylenedioxy protons is due to the trans/gauche conformational change of the O-CH 2 -CH 2 -O torsion angle.…”

“…The variation of the Xe@2 chemical shift according to the nature of the counterion indicates a different electronic density around the caged noble gas and/or a different cryptophane conformation. These two mechanisms were already invoked for explaining a modification of vibrational circular dichroism spectra [17] or chemical shift variations under xenon binding. [24] From the 1 H NMR spectra of 2 in the degassed solutions (not shown), whatever the counterion, two remarks can be made.…”

“…Also this assumption was put forward for explaining vibrational circular dichroism spectra in the presence of small neutral molecules. [17] Finally, this assumption is reinforced by the ionic radius of Cs + (1.67 ) larger than that of the other alkali metals (K + r ionic = 1.33 ; Na + r ionic = 0.97 ; Li + r ionic = 0.68 ) which, as shown by DFT calculations of a free molecule, can more efficiently block the entrance [17] or could allow its stronger binding by the phenate groups, thus forbidding xenon complexation. Other spectroscopic arguments substantiate this interpretation: 1) The strong variation of the Xe@2 chemical shift as a function of the counterion already evidences a change in the cryptophane structure and electronic density and 2) The observation of slow exchange conditions for either aromatic or aliphatic or axial protons of the CTV according to the cation used illustrates a change in the chemical equilibria between the different conformers in particular for the cryptophane linkers.…”

“…This is in agreement with the results obtained by vibrational circular dichroism. [17] Another conclusion is that the other cations strongly affect the xenon binding to compound 2. A priori, two types of interactions between cations and 2 can be figured out.…”

“…The tendency is in complete agreement with the above-reported structural interpretation, since the larger the ion radius, the bigger its affinity to the cryptophane. The size of the counterion is therefore a key parameter, as noticed recently using circular dichroism methods in reference [17].…”