Calix[6]arene Tris-carboxylic Acid Derivatives: X-ray and NMR Characterization of their Remarkable Host-guest Properties Toward Ammonium Ions

Abstract

The ability of calix[6]arene tris-carboxylic acid derivatives to include ammonium guests has been investigated both in solution and in the solid state. NMR studies and crystallographic data showed that the highly flexible calix[6]arene structures can be shaped in a well defined cone conformation thanks to the formation of an ion-paired cap between the carboxylate groups of the calixarene and their ammonium counter-ions. The resulting supramolecular edifices exhibit remarkable host-guest properties toward ammonium ions even in polar and protic solvents. The recognition process has been rationalized in the solid state by the combination of hydrogen bonding, electrostatic and CH–π interactions, and a remarkable C ₃-complementarity between the well-organized binding carboxylates of the host and the ammonium guest. Very interestingly, the endo-cavity complexation of large polycyclic ammonium ions as well as bioactive ammonium ions has been clearly demonstrated through NMR spectroscopy. Finally, the tuning of the nature of the ammonium ions involved in the supramolecular cap led to highly responsive molecular receptors.

Keywords:

• Calix[6]arene
• Ammonium ions
• Supramolecular chemistry
• Molecular receptor
• Host-guest systems

Acknowledgements

We thank Pr. Olivia Reinaud for helpful discussions. Part of this work was supported by the French Ministry of Research and New Technologies.

Notes

^∥∥ The ¹H NMR spectra of 1 ^{− 3H+, 3tBuNH3+} and 2 ^{− 3H+, 3tBuNH3+}, recorded upon similar conditions (CDCl₃, 294 K, 3.5 mM), show that these compounds possess opposite flattened cone conformation. Indeed, in contrast to 2 ^{− 3H+, 3tBuNH3+} (Fig. 4a), the methoxy groups of 1 ^{− 3H+, 3tBuNH3+} are directed toward the inside of the cavity.

^§§ The NMR studies of their stability were conducted in DMSO-d₆ at 294 K after addition of a slight excess of PrNH₂ (5 equiv.) to 1 and 2 and in CD₃OD at 260 K after addition of an excess of PrNH₂ (ca. 20 equiv.) to 1 and 2.

^¶¶ The NMR pattern of the calixarene core of reveals to be dissymmetric at 294 K (see the Supporting Information) but reflects a pseudo-C_3v symmetry at 330 K. It may be rationalized by a slow exchange (compared to the NMR time scale) of this bulky secondary ammonium ion between the three binding carboxylates.

^‡‡ It is noteworthy that the chirality of the racemic guest is not sensed by the calixarene core, since the host-guest adduct displays a C _3v symmetrical NMR pattern.

^†† The CIS values were determined after addition of an excess of the free amine R′NH₂ into a CDCl₃ solution of the calixarene host (i.e. 1 or 2). CIS were defined as Δδ = δ(complexed ammonium ion) − δ(free amine).

^# An additional hydrogen bond involving a carboxylate group and a molecule of CHCl₃ is observed in the X-ray structure. Hence, the stabilization of the dimeric self-assembly takes place through a network of 20 hydrogen bonds.

^∥ It is noteworthy that, at low temperature, no endo-complexation of small neutral polar molecules (i.e. EtOH, DMF or imidazolidin-2-one) was observed with 1 or 1 ^− 3H+ (formed by addition of 3 equiv. of the bulky tBuNH₂), showing that these hosts include ammonium guests specifically.

^§ In the case of the propylammonium ion, a NOESY experiment confirmed that the high-field peaks belong to a guest and allowed us to attribute all the resonances of the guest (see the Supporting Information in Appendix).

^¶ Similarly, the signal of the included guests was down-field shifted. This is in good agreement with an increasing acidity of the ammonium group of the guests upon a total deprotonation of the hosts.

^‡ Since the in and out exchange of the ammonium ion is slower than the NMR time scale at 294 K, the host-guest complex should possess a high K_ass value.

^† Resonances at δ_CH2N = 3.22 and 3.03 ppm (for R′ = Et and Pr, respectively) clearly indicate the presence of one equivalent of .