Non-Symmetrical Tetradentate Mixed Halogen Bonding-Hydrogen Bonding Macrocycles for Anion Recognition in Aqueous-Organic Media

Abstract

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.