Non-Symmetrical Tetradentate Mixed Halogen Bonding-Hydrogen Bonding Macrocycles for Anion Recognition in...

The prevalence of anions in biological systems, the environment, and industrial processes has driven the development of synthetic receptors capable of their selective recognition and detection. As a result of high hydration energy, the diversity in shape, and the pH-dependent nature of anions, such receptors require a highly preorganized binding site decorated with complementary multiple noncovalent interactions to stabilize anion-receptor complexation. In this study, a series of charge-neutral tetradentate macrocycles with non-symmetrical structures containing both halogen bonding (XB) iodotriazole and hydrogen bonding (HB) triazole donors were prepared via a stepwise CuAAC macrocyclization reaction. The non-symmetrical XB/HB macrocycles displayed increased anion binding affinities and contrasting anion selectivities in comparison to a symmetrical all HB macrocycle analogue, even in the presence of water, but still exhibited halide binding less strongly than the analogous all XB macrocycle. As a result of the macrocyclic effect and the number and nature of donor groups, the non-symmetrical XB/HB macrocycles exhibited the largest enhancement of Cl^- binding compared to their acyclic XB analogues. DFT computational studies revealed the preferential binding geometry where the halide anion was primarily bound to the XB binding site through two σ-hole interactions at two adjacent iodine sites and supplemented by one H─bond interaction at one of the C─H triazole sites.