Unlocking A New Biological Interface of Chiral Supramolecular Helical Polymers

Supramolecular helical polymers and helicates are two well-known and structurally different families of materials that share the same chiral axial motif, the helix. In this work, we describe how it is possible to design a molecule capable of folding in water into either of these two supramolecular entities. To do that we prepared a C3 symmetric benzene-1,3,5-triyltrimethanamine (BTMA) core conjugated to three peptide sequences, i.e. H-Arg-βAla-Bpy-βAla-Bpy-NH2 (BTMA-1). This molecule comprises all the structural requirements to self-assembly in water either into a chiral supramolecular helical polymer or into a chiral discrete helicate in the absence/presence of CoII ions in the aqueous media. We demonstrated that the discrete CoII peptide helicate folded can recognize DNA three-way junctions with high affinity and selectivity against canonical DNA and, moreover, that this recognition process can be operated from both the preformed discrete chiral peptide helicate and the chiral supramolecular helical polymer. Finally, we also proved that the labile CoII peptide helicate can be oxidized in situ in water to generate the corresponding kinetically inert CoIII derivative, which also possess selective 3WJ recognition capabilities. This study opens a new scenario in the biological applications of chiral supramolecular helical polymers, demonstrating that can be maintained inactively dispersed in water with time and further transformed into discrete bioactive molecules by an external stimulus.