Evidence of Nanotubular Self-Organization in Solution and Solid States of Heterochiral Cyclo 1:1 [α/α‑<i>N</i>^α‑Bn-hydrazino]mers Series

The cyclization of heterochiral 1:1 [α/α-<i>N</i>^α-Bn-hydrazino]­mers leads to the corresponding cyclotetramer and cyclohexamer <b>3</b> and <b>4</b>. X-ray crystallographic analysis of <b>3</b> unveils its ability to self-assemble into nanotubular structures. Further experiments conducted in the solid state through SEM analyses demonstrate the capability of <b>3</b> and <b>4</b> to form aerogels consisting of a network of nontwisted fibers, thus confirming the presence of self-organization within this series of mixed-hydrazinopeptides. Subsequent FTIR and NMR studies demonstrate the presence of an equilibrium between monomeric (intramolecular H-bonds) and nanotubular (intermolecular H-bonds) forms in solution. This equilibrium can be modified by varying the solvent

Spontaneous Self-Assembly of Fully Protected Ester 1:1 [α/α‑<i>N</i>^α‑Bn-hydrazino] Pseudodipeptides into a Twisted Parallel β‑Sheet in the Crystal State

Previous studies have demonstrated that amidic α/β-pseudodipeptides, 1:1 [α/α-<i>N</i>^α-Bn-hydrazino], have the ability to fold via a succession of γ-turn (C₇ pseudocycle) and hydrazinoturn in CDCl₃ solution, their amide terminals enabling the formation of an intramolecular H-bond network. Despite their lack of a primary amide terminals allowing the formation of the hydrazinoturn, their ester counterparts <b>1</b>–<b>4</b> were proven to self-assemble into C₆ and C₇ pseudocycles by intramolecular H-bonds in solution state and into an uncommon twisted parallel β-sheet through intermolecular H-bonding in the crystal state to form a supramolecular helix, with eight molecules needed to complete a full 360° rotation. Such self-organization (with eight molecules) has only been observed in a specific α/α-pseudodipeptide, depsipeptide (Boc-Leu-Lac-OEt). Relying on IR absorption, NMR, X-ray diffraction, and CD analyses, the aim of this study was to demonstrate that stereoisomers of ester 1:1 [α/α-<i>N</i>^α-Bn-hydrazino] pseudodipeptides <b>1</b>–<b>4</b> are able to self-assemble into this β-helical structure. The absolute configuration of the asymmetric C^α-atom of the α-amino acid residue influences the left- or right-handed twist without changing the pitch of the formed helix