Dual Binding Mode of Methylmethanetriacetic Acid to Tripodal Amidopyridine Receptors

A series of tripodal amidopyridine receptors capable of selective recognition of methylmethanetriacetic acid (MMTA) in organic solvents is described. Intramolecular hydrogen-bonding groups, built
into some of the receptors, were designed as preorganization devices. Binding was studied by NMR
titration, variable temperature NMR experiments, 2D-NMR, isothermal titration calorimetry, and
single-crystal X-ray crystallography. The results reveal that a balancing act between inter- and
intramolecular hydrogen-bonding interactions in the complexes governs both the dynamics and
the geometry of binding. Receptor 1b (without intramolecular hydrogen-bonding groups) features
a simple symmetric MMTA binding geometry with optimal enthalpic interactions. In sharp contrast,
receptor 1a (with intramolecular hydrogen-bonding groups) reveals a temperature-dependent dual
binding mode where MMTA can bind in two completely different geometries. The two solution
binding geometries of 1a·MMTA were unraveled by NMR experiments and correlated to the X-ray
structures.