Spontaneous Self-Assembly of Fully Protected Ester 1:1 [α/α-Nα-Bn-hydrazino] Pseudodipeptides into a Twisted Parallel β-Sheet in the Crystal State.

Abstract

Previous studies have demonstrated that amidic α/β-pseudodipeptides, 1:1 [α/α-Nα-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 1-4 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-Nα-Bn-hydrazino] pseudodipeptides 1-4 are able to self-assemble into this β-helical structure. The absolute configuration of the asymmetric Cα-atom of the α-amino acid residue influences the left- or right-handed twist without changing the pitch of the formed helix.