What drives enhanced chloride recognition of squaramide-based receptors over urea and thiourea? A computational exploration in the gas-phase and various solvents

Significant progress in anion recognition has been achieved through the development of synthetic receptors. Urea-, thiourea-, and squaramide-based molecules, known for hydrogen-bonding capabilities, have gained prominence in supramolecular chemistry. The superior anion recognition of squaramide-based receptors, compared to urea- and thiourea-based ones, is repeatedly attributed to the crucial involvement of CH fragments. This study computationally investigates chloride recognition by nine symmetric urea-, thiourea-, and squaramide-based receptors, focusing on solvent effects, interactions, and intrinsic affinity. The findings suggest that while CH fragments aid anion recognition in squaramide-based receptors, the absence of steric repulsion and the presence of attractive forces between amide NH groups in squaramide, unlike in urea and thiourea receptors, significantly enhances anion-binding ability. Although solvation energy becomes less favorable from urea to squaramide, negative gas-phase Gibbs free energy drives complex formation. The accuracy of computational results is validated by excellent correlation between experimental and calculated formation constants.