A spirocyclic backbone accesses new conformational space in an extended, dipole-stabilized foldamer

Abstract

Most aromatic foldamers adopt uniform secondary structures, offering limited potential for the exploration of conformational space and the formation of tertiary structures. Here we report the incorporation of spiro bis-lactams to allow controlled rotation of the backbone of an iteratively synthesised foldamer. This enables precise control of foldamer shape along two orthogonal directions, likened to the aeronautical yaw and roll axes. XRD, NMR and computational data suggest that homo-oligomers adopt an extended right-handed helix with a pitch of over 30 Å, approximately that of B-DNA. Compatibility with extant foldamers to form hetero-oligomers is demonstrated, allowing greater structural complexity and function in future hybrid foldamer designs.

Non‐Covalent Interactions Enforce Conformation in Switchable and Water‐Soluble Diketopiperazine‐Pyridine Foldamers

“…In our previous studies dipolar repulsion between adjacent monomers was used as the primary determinant of conformation, specifically between azenes and imidazolidine‐2‐one [6] and spirocyclic bis‐lactam [7] linkers. Related systems undergo acid‐mediated switching between an extended and helical conformation [5k,o] .…”

“…Protonation of the pyridines would subvert this interaction and lead to the manner of switching outlined in Figure 1A. We have utilized the principal axes of aviation to convey the conformational effects of monomers within foldamers [7] . Here, we anticipate that the substitution pattern on the azene linker and dipolar repulsion effects will achieve control about both the yaw and roll axes.…”

Non‐Covalent Interactions Enforce Conformation in Switchable and Water‐Soluble Diketopiperazine‐Pyridine Foldamers

“…We have utilized the principal axes of aviation to convey the conformational effects of monomers within foldamers. [7] Here, we anticipate that the substitution pattern on the azene linker and dipolar repulsion effects will achieve control about both the yaw and roll axes.…”

“…[4] As a result, switching within foldamers has been reported in response to diverse stimuli including light, solvent polarity and ionbinding. [1a,5] In our previous studies dipolar repulsion between adjacent monomers was used as the primary determinant of conformation, specifically between azenes and imidazolidine-2-one [6] and spirocyclic bis-lactam [7] linkers. Related systems undergo acid-mediated switching between an extended and helical conformation.…”

“…In our previous studies dipolar repulsion between adjacent monomers was used as the primary determinant of conformation, specifically between azenes and imidazolidine‐2‐one [6] and spirocyclic bis‐lactam [7] linkers. Related systems undergo acid‐mediated switching between an extended and helical conformation.…”