LAUSR

Allosteric regulation of protein structure and function is a hallmark of biology. The structures of protein-like abiological foldamers have been subject to allosteric control, however, regulation of their function is rare. We report this behavior using a photoactive foldamer following the discovery that small and large anions select between single and double helical structures, respectively. Correspondingly, these anions activate different functions in the photofoldamer; small anions turn on photoregulation of anion concentrations while large anions turn on chiroptical switching of quaternary structure. For this demonstration, we used an aryl-triazole based photofoldamer in which the light-driven trans-cis isomerization of azobenzenes alters intrastrand π-π contacts while the triazoles define the allosteric anion-binding site. Binding to 11 anions of increasing size was quantified (Cl-, Br-, NO2-, I-, NO3-, SCN-, BF4-, ClO4-, ReO4-, PF6-, SbF6-). Contrary to expectations that single helices will expand to accommodate larger and larger guests, this behavior only occurs for smaller anions (Cl- to NO3-; <45 Å3) beyond which the larger anions form double helices (SCN- to SbF6-; >45 Å3). With small anions, the single helix regulates anion concentrations when the azobenzenes are photoswitched. The binding of large anions favors a chiral double helix and activates light-driven switching into racemic single helices thereby modulating the quaternary structure and chiroptical activity. This work shows how complex multifunctional outcomes emerge when allosteric changes in structure are expressed in intrinsically functional foldamers.