Modular synthesis of zinc(II)-bis(triazole) recognition sites for the conformational control of foldamers

Abstract

Zinc(II) bis(triazolyl)(pyridyl)amine (Zn(BTPA)) complexes on the end of α-amino-iso-butyric acid (Aib) foldamers are able to transfer chirality from bound anions to the helical foldamer body. Zn(BTPA) could be obtained by simple synthetic methodology that allowed a range of functional groups to be installed around the binding site, exemplified with a fluorophore, a macrocyclic bridge and Aib itself. Changing functional group did not prevent chiral ligands from controlling foldamer conformation, although differences in complexation kinetics and equilibria were observed. Addition of acetate gave a 2:1 foldamer:acetate intermediate at sub-stoichiometric acetate; a similar intermediate was implied during titration with Boc-Pro. A bulkier phosphate ligand or a more sterically hindered site did not form similar intermediates. The modular construction of Zn(BTPA)-capped foldamers will allow these conformational relays to be installed in a wide range of biomimetic constructs.