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

Zinc-coordinated bis(dipicolylamine) (<b>ZnBDPA</b>) and its phenoxy derivative (<b>ZnPhenoxyBDPA</b>) 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. <b>TyramineBDPA</b> is a very useful version of the <b>ZnPhenoxyBDPA</b> scaffold, with a reactive primary amine for subsequent conjugation chemistry. Despite its utility and structural simplicity, the preparation and purification of <b>TyramineBDPA</b> can be challenging, especially for inexperienced labs. Presented here is a reproducible, three-step procedure for synthesising and purifying <b>TyramineBDPA</b> 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 <b>TyramineBDPA</b> receptors for supramolecular research and development. Proof of utility was gained by conjugating <b>TyramineBDPA</b> to a pyrene fluorophore to create a fluorescent <b>ZnBDPA</b> 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.