Tuneable anion recognition at the lower rim of resorcin[4]arenes: strength, selectivity, and transport

Anions are involved in nearly all biological processes and play a cardinal role in various industrial environments. The study of anion complexation is of significant academic interest, forming a fundamental pillar of supramolecular chemistry and finding applications in multiple areas such as sensing, catalysis, transport, etc. Furthermore, the sequestration of ecologically relevant anions such as chlorides, bisulfates, and nitrates from the environment would pose a huge benefit to the sustainable reprocessing of these anions. We recently discovered that resorcin[4]arenes, polyphenolic macrocyclic compounds traditionally known as cation receptors, can also bind anions when strong electron-withdrawing substituents are introduced at the upper rim with high apparent binding affinities. 

In the current study, we focus on the synthesis and binding properties of other derivatives with electron-withdrawing substituents (-CN, -CHO, -Br) at the upper rim, along with modifications at the lower rim of resorcin[4]arenes. We found a substantial increase in the binding affinity, which is attributed to the -CN group providing a strong electron-withdrawing effect through resonance and inductive effect, hence polarising the C-H hydrogen bond strongly enough to bind anions. Although the Hammett parameters state the opposite, this effect is more pronounced than the presence of -the NO₂ substituent, at the same position, studied earlier. This makes macrocycle 4 the most effective anion receptor in the family of resorcinarenes, as per our knowledge. The log K values correlate well with the theoretically predicted ESP values for the receptors.

Furthermore, the modifications at the lower rim enabled us to present a conclusive study regarding the changes in modes of binding affinity and selectivity of the receptors, as achieved in macrocycle 6, which was found to bind HSO₄^- exclusively, with a selectivity factor of 17 over similar tetrahedral oxyanions in THF/10% D₂O. The advantages of using DFT calculations for the engineering of the receptor and prediction of binding properties are also stressed.