Superfast and highly selective water transport by hybrid aquapentamers incorporating a non-helicity codon

H-bonded helically folded aromatic foldamers rely on the precise formation of H-bonds between each helicity codon and its neighboring codons to maintain their structure. We report here for the first time that the phenyl group, referred to as a non-helicity codon due to its inability to form H-bonds, does not necessarily disrupt the helical structure. Specifically, we modified our recently reported pyridine-based aquapentamers by sequentially replacing each of the five pyridine residues with a phenyl group, creating a series of five hybrid pentamers. The phenyl groups, unable to form H-bonds with the adjacent N-H bonds of the amides, introduce H-bond defects along the helical backbone. Despite these defects, three out of five pentamers still adopt a helical structure and function as highly selective and ultra-fast abiotic water channels, with the most efficient channel achieving a water transport rate of 1.8 × 10⁹ H₂O s⁻¹ per channel—approximately 30% of aquaporin Z's capacity.