Sequence-Controlled Stimuli-Responsive Single–Double Helix Conversion between 1:1 and 2:2 Chloride-Foldamer Complexes

The
primary sequence in biopolymers carries the information to
direct folded secondary structures, to modulate their stabilities,
and to control the resultant functions. Our ability to encode
such information into nonbiological oligomers and polymers, however,
is still limited. Here, we describe a C2-symmetric aryl-triazole foldamer that assembles into a chloride-templated
2:2 double helix, and the discovery that its interconversion with
the simpler 1:1 single helix can be driven by solvent quality, temperature,
and concentration. We use single-site substitutions in the 13-residue
sequence (two terminal sites and one central site) to reveal that
the stability of the double helix is largely dictated by the differences
in the anion binding power between single and double helices as well
as the location of the modified residues. Specifically, placement
of stabilizing CH···Cl– hydrogen-bonding
interactions at the chain ends in the form of bisamide phenylene residues
is found to highly favor the double helix. While the burial of π
surfaces and the solvophobic effect also help to stabilize the double
helix, their role was found to be less sensitive to the modifications
considered. This understanding of how chemical information is programmed
into the primary sequence provides a powerful tool for controlling
structure and properties of abiological foldamers.