Bicyclic anionic receptors for carboxylates in water

TL;DR

This paper presents a new method to create receptors that can bind carboxylates in water, with potential applications in biology and medicine.

Contribution

A general approach to synthesize water-soluble carboxylate receptors using a bicyclic system and Cu(i)-catalyzed reactions.

Findings

Three receptors were synthesized and showed Ka up to ∼400 M−1 for carboxylates in water.

The receptors can bind both carboxylates and polar inorganic anions at near-neutral pH.

The method allows for versatile synthesis of receptor variants for potential medical use.

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 Ka 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.

A generalisable reaction sequence converts diamines into carboxylate receptors which can enclose their substrates and operate effectively in water.

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