Binding interactions between 3-aryl-1,2,4-oxadiazol-5-ones and a trisimidazoline base

The use of 1,2,4-oxadiazol-5-ones, a recently developed class of bioisoster ic replacements for carboxylic acids in medicinal chemistry, as binding lig ands in supramolecular complexes is reported and has been exemplified by th e formation of non-covalent complexes between acidic 3-aryl-1,2,4-oxadiazol -5-ones and an imidazoline base, 1,3,5-tris(4,5-dihydroimidazol-2-yl)benzen e 1. The X-ray crystal structure of complex 6d illustrates how the carbonyl oxygen and the nitrogen atom in the position alpha to the carbonyl group o f the heterocyclic ligand are hydrogen-bonded to the NH groups of tris(imid azoline) 1. A combination of H-1 NMR dilution studies and electrospray mass spectrometry-based competition experiments shows that 1,2,4-oxadiazol-5-on es bind more strongly to receptor 1 than a comparable benzoate.