Anti‐Hofmeister Anion Selectivity via a Mechanical Bond Effect in Neutral Halogen‐Bonding [2]Rotaxanes

Exceptionally strong halogen bonding (XB) donor‐chloride interactions are exploited for the chloride anion template synthesis of neutral XB [2]rotaxane host systems which contain perfluoroaryl‐functionalised axle components, including a remarkably potent novel 4,6‐dinitro‐1,3‐bis‐iodotriazole motif. Halide anion recognition properties in aqueous‐organic media, determined via extensive (1)H NMR halide anion titration experiments, reveal the rotaxane host systems exhibit dramatically enhanced affinities for hydrophilic Cl(−) and Br(−), but conversely diminished affinities for hydrophobic I(−), relative to their non‐interlocked axle counterparts. Crucially, this mechanical bond effect induces a binding selectivity which directly opposes Hofmeister bias. Free‐energy analysis of this mechanical bond enhancement demonstrates anion recognition by neutral XB interlocked host systems as a rare and general strategy to engineer anti‐Hofmeister bias anion selectivity in synthetic receptor design.