Bis-urea anion receptors: influence of receptor structure and anion nature on binding affinity and stability

Complexation behavior of bis-urea receptors bearing nitro substituent at different proximities from urea binding site was investigated using isothermal titration calorimetry (ITC) and ¹H NMR (Nuclear Magnetic Resonance) titration experiments. Their binding interactions with fluoride (F^-), acetate (OAc^-), and dihydrogen phosphate (H₂PO₄ ^-) anions were examined to evaluate affinities, stoichiometries, and thermodynamic parameters. The nature of the anion and the position of the nitro substituent significantly influenced receptor binding ability. Receptors with <i>ortho</i>-nitro groups underwent decomposition upon interaction with F^-, forming 2-benzimidazolinone cyclic urea as evidence from relatively large positive enthalpy (Δ<i>H</i>° = 13.78 kJ mol^-1) and entropy (Δ<i>TS</i>° = 30.90 kJ mol^-1). Furthermore, X-ray diffraction analysis revealed that the cyclic urea engages in complexation with the fluoride anion. This degradation was suppressed in <i>meta</i>-substituted analog. Notably, <i>meta</i>-nitro receptor exhibited high binding affinity toward acetate (Δ<i>H</i>° = -27.73 kJ mol^-1), while H₂PO₄ ^- binding for all receptors showed large entropic contributions, due to the geometry and size of the anion. These results offer insights into designing selective and stable anion receptors.