Molecular clips based on propanediurea. Exceptionally high binding affinities for resorcinol guests

A series of new receptor molecules derived from 2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-dione (propanediurea) is described. These molecules possess a cavity which is defined by two nearly parallel aromatic side walls positioned on top of a bis-urea framework. The resulting “U-shaped” clip molecules are ideal hosts for the complexation of flat aromatic guest molecules. The affinity of these new propanediurea based molecular clips for dihydroxybenzene derivatives is exceptionally high, with association constants up to Ka = 2 400 000 L mol-1. Comparison of the binding mechanism of a variety of clip and half clip hosts, in conjunction with NMR, IR, and X-ray studies, has enabled the reason for this high binding to be elucidated. It is shown that subtle sub-angstrom changes in the geometry of the clip molecules have a great impact on their binding properties