Synthesis of tyramine bis(dipicolylamine), a versatile synthetic receptor scaffold for oxyanion recognition

Zinc-coordinated bis(dipicolylamine) (ZnBDPA) and its phenoxy derivative (ZnPhenoxyBDPA) are well-known as synthetic receptors with strong affinity for oxyanions, especially phosphorylated biomolecules. Over the last two decades, these synthetic receptors have found broad utility in diverse supramolecular research fields where they enable oxyanion binding, sensing, transport, imaging, or catalysis. TyramineBDPA is a very useful version of the ZnPhenoxyBDPA scaffold, with a reactive primary amine for subsequent conjugation chemistry. Despite its utility and structural simplicity, the preparation and purification of TyramineBDPA can be challenging, especially for inexperienced labs. Presented here is a reproducible, three-step procedure for synthesising and purifying TyramineBDPA on the gram scale, starting from inexpensive and commercially available tyramine. This optimised synthesis will help investigators prepare a wide range of zinc and related dinuclear TyramineBDPA receptors for supramolecular research and development. Proof of utility was gained by conjugating TyramineBDPA to a pyrene fluorophore to create a fluorescent ZnBDPA receptor that revealed new insight regarding receptor clustering under binding conditions where the receptor concentration is high relative to the concentration of phosphate recognition target.