Guest-Induced Conformational Switching in “One Wall” Calix[4]pyrrole Cavitands Functionalized with an Inwardly Directed Carboxylic Acid

Abstract

We report the design, synthesis, and conformational analysis of two aryl-extended calix[4]pyrrole (AE-C[4]P) cavitands that feature a single methylene bridge and an opposed aromatic bridging wall with an inward-facing carboxylic acid. Inspired by Rebek’s introverted acid motif, these cavitands were developed to explore guest-induced conformational switching between “equatorial” and “axial” orientations of the bridging aromatic wall. Binding studies with N-oxide guests, capable of monotopic or ditopic hydrogen bonding, revealed that the nature of the bridging aromatic spacer critically governs the host behavior. The benzimidazole-based cavitand showed strong affinity for DABCO mono-N-oxide but resisted conformational change. In contrast, the quinoxaline–imidazole analogue underwent a solvent-dependent switch from “equatorial” to “axial” geometry upon binding 4-carboxy-pyridine-N-oxide guest. This switching is driven by the ditopic binding of the guest and stabilized by two intramolecular CH···lone pair interactions in the axial conformer of the complex. DFT calculations supported the experimental results. The reported findings highlight key structure–function relationships in calix[4]pyrrole cavitands and establish a general strategy for designing guest-responsive molecular containers capable of conformational switching.