# Tunable Anion Recognition at the Lower Rim of Resorcin[4]arenes: Strength, Selectivity, and Transport

## TL;DR

Researchers developed modified resorcin[4]arenes that can selectively bind and transport anions, offering insights into designing better anion transporters.

## Contribution

Modified resorcin[4]arenes with electron-withdrawing groups and hydroxyl-terminated alkyl chains enable tunable anion binding and transport.

## Key findings

- CN-substituted resorcin[4]arene shows the highest anion binding affinity (K_a(Cl–, THF) = 7 × 10⁵ M⁻¹).
- Hydroxyalkyl-footed receptors exhibit exceptional selectivity for HSO₄⁻ over other oxyanions.
- Nitro-substituted resorcin[4]arene is the most effective chloride transporter in transmembrane studies.

## Abstract

Selective anion binding and transport are crucial in
many chemical
and biological settings. CH-bonding receptors–which rely on
nonclassical CH···anion hydrogen bonds, offer a pH-independent
alternative to conventional hosts; however, their design is challenged
by the inherently weak nature of CH···anion interactions.
In this study, we present modified resorcin[4]­arenes as versatile
scaffolds to address this challenge. By introducing electron-withdrawing
groups (EWGs) at the upper rim, we convert π–electron-rich
resorcin­[4]­arenes into potent anion receptors. A series of resorcin[4]­arenes
bearing −Br, −CHO, −NO2, and −CN
substituents exhibit a systematic enhancement in anion binding affinity,
reaching the highest value in the series for the CN-substituted receptor: K
a(Cl–, THF) = 7 × 105 M–1. The logK
a values correlate with the electrostatic potential (ESP) at the binding
site, calculated by DFT methods. In addition, the incorporation of
hydroxyl-terminated alkyl chains at the lower rim promotes the formation
of higher-order complexes and further boosts anion binding, even in
competitive aqueous–organic media. These hydroxyalkyl-footed
receptors display exceptional selectivity for HSO4
–, with a selectivity factor of 17 over similar tetrahedral
oxyanions. Transmembrane anion transport studies in large unilamellar
vesicles reveal that the nitro-substituted resorcin[4]­arene is by
far the most effective chloride transporter in this series, followed
by the CN-substituted analogue, emphasizing that the most strongly
binding receptors are not necessarily the most efficient transporters.
Detailed analysis of molecular lipophilicity potential (MLP) maps
shows that subtle differences in upper- and lower-rim polarity, as
well as excessive hydrophilicity at the lower rim, can diminish transport
efficiency by hindering membrane reorientation or promoting interfacial
anchoring. These mechanistic and structure–activity insights
provide clear design principles for developing next-generation CH-bonding
transporters with improved performance. Collectively, these results
highlight the potential of resorcin[4]­arenes as tunable platforms
for tailoring anion binding strength, selectivity, and anionophoric
properties through simple peripheral modifications.