High Affinity Carboxylate Binding Using Neutral Urea-Based Receptors with Internal Lewis Acid Coordination.

Uncharged receptors for anions and cations have many potential applications ranging from membrane transport carriers for ion-selective electrodes to reaction catalysts.1 As a consequence, there is a need to design and synthesize neutral receptors with high binding affinities and/ or high binding selectivities. Unlike cation receptors, there are essentially no examples of biotic, low molecular weight hosts for anions.2 Synthetic anion receptors have to be designed de novo using the principles of molecular recognition. The neutral anion-receptors reported to date have employed either Lewis acid-base,3 hydrogen bonding,4 and/or ion-dipole interactions.5 Most of the hydrogen bonding systems have used urea groups as the recognition motif. Urea-based hosts have been shown to associate with carboxylates, phosphates, and sulfonates to produce bidentate hydrogen-bonded complexes such as 1.4 In this paper we describe a structural design strategy that greatly improves the anion binding ability of neutral urea-based receptors. It is likely that this strategy can be incorporated into the designs of other amide-based molecular recognition systems. The formation of supramolecular complex 1 is driven primarily by hydrogen bonding and ion-dipole interactions.6,7 These bonding interactions can be strengthened by cooperative polarization of the urea group, which is accomplished by coordinating the urea carbonyl to a Lewis acid.8 A major design challenge is to ensure that the Lewis acid is held in the correct spatial orientation with a high effective molarity. One possible solution is the Lewis acid-urea conjugate 2. In line with our current interest in organoboron receptors,9 we designed boronate-urea 3 as a first-generation example of this receptor class. The valence bond structure for receptor 3 can be represented by two limiting forms, 3a or 3b. Prior to this study there was literature precedent to suggest that 3b would be the major resonance contributor.10