Electronic Modulation of Bromide and Iodide Recognition in Functionalized Hexacationic Cages: A Comparative Theoretical Study of meta - and para -Frameworks

Abstract

Understanding the factors governing anion recognition is essential for the rational design of supramolecular receptors with enhanced affinity and selectivity. The recognition of Br– and I– by two families of hexacationic cages, meta- (MH6+) and para- (PH6+) derivatives bearing electron-donating (−NH2) or electron-withdrawing (−NO2) substituents at different chemical positions, was investigated using Density Functional Theory (DFT) calculations. The preferential recognition of Br– over I– is primarily associated with its smaller ionic radius, which enables a better geometric fit within the cavity and consequently leads to reduced Pauli repulsion together with stronger electrostatic and orbital interactions. Most substitutions weaken host–guest recognition primarily because of less favorable electrostatic and orbital interactions, such as (C or, chiefly, N)–H···Br– and (heteroatom or C)···Br–; however, specific substituents significantly enhance Br– binding. The para-derivatives exhibit the strongest interaction energies owing to the cooperative reinforcement of non-covalent (C or, mainly, N)–H···Br– interactions. In contrast, one meta-derivative follows a distinct recognition mechanism, in which the conventional Br– → σ*(N–H) interaction is replaced by charge transfer toward a σ*(C–NO2) orbital, giving rise to an unusually strong C···Br– interaction with partial covalent character and pronounced orbital stabilization. These findings reveal how the cage framework and electronic substitution cooperatively modulate chemical interactions, providing molecular design principles for highly efficient supramolecular halide receptors.