Azulene-Based Macrocyclic Receptors for Recognition and Sensing of Phosphate Anions

Herein we report the synthesis and detailed studies of the anion-binding properties of two 20-membered macrocyclic tetramide receptors: one symmetrical, containing two identical azulene-based bisamide units, the other a hybrid, containing a dipicolinic bisamide unit and an azulene-based bisamide unit. Analysis of the crystal structures of the macrocyclic receptors revealed their preference for adopting similar well-preorganized bent-sheet conformations, both as free receptors and in their complexes with anions. Studies of the optical properties of both receptors revealed abilities to selectively sense phosphate anions (H₂ PO₄^- , HP₂ O₇^3- ), allowing for naked-eye detection of the presence of these guests in DMSO. Binding studies in solution confirmed that the receptors bind strongly to a series of anions even in highly demanding media, such as mixtures of DMSO with water or with methanol. Comparison of the anion affinity of linear analogues with that of the macrocyclic receptors evidenced the importance of macrocyclic topology. Quantitative analysis revealed that the macrocyclic receptors are selective for H₂ PO₄^- over other anions. The affinity to H₂ PO₄^- seen for the symmetrical receptor, containing two azulene-based subunits, is much higher than for the hybrid macrocycle containing both the azulene-based and pyridine-derived subunits. This highlights that the azulene-based building block serves efficiently as both a binding site and a structure-preorganizing motif.