Anion-Π Meets H-Bonding: Tuning Synergy Through the Flexibility-to-Preorganization Transition in Anion Receptor Design

This study focuses on a series of receptors incorporating urea and pentafluoropyridine motifs to investigate the synergistic combination of hydrogen bonding and anion-π interactions for anion recognition. Three receptors with various spacers are synthesized to evaluate the influence of molecular preorganization and rigidity on anion binding. Flexible receptor 1 and rigid receptors 2 and 3 are synthesized following a two-step protocol, involving the construction of the urea fragment from isocyanate precursors and a nucleophilic aromatic substitution to install the tetrafluoropyridine motif as key steps. Computational analyses (density functional theory (DFT), noncovalent interaction (NCI) plots), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry are employed to assess structural features and binding performance. DFT calculations reveal that all receptors allow complexation with chloride through dual urea and π-anion sites. Structural rigidity in receptor 3 shows enhanced binding efficacy due to steric strain and additional CH···Cl⁻ interaction from its naphthalene core. NMR titrations provide qualitative insights into binding events, with receptor 3 exhibiting the largest shieldings for all H-bonds, in line with theoretical predictions. Mass spectrometry and collision-induced dissociation experiments confirm receptor–anion complexation, with fragmentation patterns supporting the relative binding strengths. The overall ranking is 3 > 2 > 1, corroborating computational and experimental data.