Bicyclic anionic receptors for carboxylates in water

Abstract

The selective recognition of carboxylates in water, the biological solvent, could have various applications in biology and medicine. Of particular interest is the design of antibiotics which mimic the glycopeptides such as vancomycin through binding C-terminal peptide units involved in bacterial cell wall synthesis. Here we report a general approach to carboxylate receptors with structures capable of encapsulating and interacting with all parts of their substrates. The synthesis involves elaboration of a diamino bridge unit into a bicyclic system incorporating a tetralactam anion binding site. Water-solubility can be achieved in a final step which introduces two dendrimeric nonacarboxylate units via Cu(I)-catalysed azide–alkyne cycloaddition. Three examples have been prepared and found to bind simple carboxylates and polar inorganic anions with K_a up to ∼400 M⁻¹ in water at near-neutral pH, despite the presence of polycarboxyl solubilising groups. Selectivities are modest, probably because of the flexible bridge units employed, but the versatile synthesis should allow access to a wide range of variants including some with potential for medical applications.