Direct Endgroup Modification of Poly(Aib)-polymers: Heterogeneous Peptide Coupling and Chiral Folding

Abstract

Helical poly(α-aminoisobutyric acid) is regarded a foldamer capable of transmitting chiral information along achiral backbones. Yet its post-polymerization modifications after ring opening polymerization (ROP) remain challenging due to its poor solubility and limited reactivity. We here report a robust strategy for end-group functionalization of poly(Aib), obtained after ROP under heterogeneous conditions, enabling efficient coupling of a wide variety of endgroups using stereochemically distinct initiators, point chiral amines, axially chiral binaphthols, and overcrowded alkene-based Feringa’s photoswitches. The resulting polymers were post-functionalized via peptide-type coupling under varying conditions, employing different carboxylic acids and coupling agents in various solvents to introduce the chemically distinct termini. MALDI-TOF mass spectrometry was used to assess purity and to monitor characteristic mass shifts associated with the respective end-group incorporation, thereby confirming successful post-polymerization modification. Circular dichroism spectroscopy further confirmed transfer of chiral information from the initiators and the preservation of the helical secondary structure after functionalization. Among the tested systems, lipoic-acid-functionalized polymers exhibited the highest coupling efficiency able to adsorb onto gold surfaces via disulfide-gold affinity, forming thin polymer films as evidenced by AFM and XPS analyses. The work establishes a versatile, heterogeneous post-functionalization strategy for tailoring helical poly(Aib) architectures with defined chiralities and surface-binding functionality, enabling the design of both static and dynamic chiral interfaces for next-generation molecular devices