Super Aryl‐Extended Calix[4]pyrroles: Synthesis, Binding Studies, and Attempts To Gain Water Solubility

We describe the synthesis of unprecedented calix[4]pyrrole receptors featuring “super aryl extended” (SAE) cavities. We elaborated the aromatic cavity provided by the αααα‐isomer of para ‐tetraiodo‐ meso ‐phenyl calix[4]pyrrole by installing ethynyl‐aryl substituents at its upper rim. We report the binding properties of the prepared SAE‐calix[4]pyrrole tetraester towards pyridyl‐ N ‐oxides. The binding data revealed the formation of thermodynamically and kinetically highly stable 1:1 complexes. The complexation‐induced chemical shifts indicated the formation of hydrogen bonds and aromatic interactions with the calix‐core adopting the cone conformation. We quantified the additional interactions established between the four terminal aryl groups and the para ‐phenyl substituent of 4‐phenyl pyridine N ‐oxide to be in the order of 1 kcal mol −1 . The complex formation rate was found to be close to the diffusion control suggesting that the free host adopted a 1,3‐alternate conformation. Finally, we attempted to gain water solubility of SAE‐calix[4]pyrroles using derivatives that display four ionizable or charged groups at their upper rims.