Effect of Stereochemistry on Chirality and Gelation Properties of Supramolecular Self‐Assemblies

Abstract

Although chiral nanostructures have been fabricated at various structural levels, the transfer and amplification of chirality from molecules to supramolecular self‐assemblies are still puzzling, especially for heterochiral molecules. Herein, four series of C2‐symmetrical dipeptide‐based derivatives bearing various amino acid sequences and different chiralities are designed and synthesized. The transcription and amplification of molecular chirality to supramolecular assemblies are achieved. The results show that supramolecular chirality is only determined by the amino acid adjacent to the benzene core, irrespective of the absolute configuration of the C‐terminal amino acid. In addition, molecular chirality also has a significant influence on the gelation behavior. For the diphenylalanine‐based gelators, the homochiral gelators can be gelled through a conventional heating–cooling process, whereas heterochiral gelators form translucent stable gels under sonication. The racemic gels possess higher mechanical properties than those of the pure enantiomers. All of these results contribute to an increasing knowledge over control of the generation of specific chiral supramolecular structures and the development of new optimized strategies to achieve functional supramolecular organogels through heterochiral and racemic systems.

Chirality Effects in Peptide Assembly Structures

“…For example, the racemic mixture of Fmoc monosubstituted cyclo-(EE) and its D-analog formed quickly recoverable thixotropic hydrogel with a significantly shortened thixotropic recovery time compared with the hydrogels formed by either enantiomer alone (Wang L. et al, 2017). In addition, the racemic gel formed by diphenylalanine-based derivative enantiomers was more mechanically robust than the gels formed by either pure enantiomer (Qin et al, 2021). On the contrary, He and coworkers got the opposite results showing that the hydrogel formed by a racemic mixture of ferrocene-diphenylalanine (Fc-FF) was mechanically weaker than the enantiopure hydrogels (Zhang et al, 2020).…”

“…These results indicate the significance of the chirality of terminal amino acid residues in determining supramolecular chirality. On the contrary, Feng and coworkers studied the assembly structures of dipeptides derivatives by connecting two dipeptide arms (FF, AA, FA, and AF) with different chirality to para-disubstituted phenyl group, and found that the supramolecular chirality was only determined by the amino acid residue adjacent to the benzene core and irrespective of the chirality of C-terminal amino acid residue ( Qin et al, 2021 ). In addition, the handedness of the nanofibers formed by bola-type dipeptides (AF) was dictated by the phenylalanine residue, not by the terminal amino acid residues ( Zheng et al, 2020 ).…”

“…Studies of L - and D -stereoisomers of amyloid peptides, such as a 22-residue segment of β 2 -microglobulin and β-amyloid peptide (Aβ40), showed that amyloid fibril formation was stereospecific: L -enantiomer was deposited on L -seeds, and enantiomers did not cross-react with each other ( Esler et al, 1999 ; Wadai et al, 2005 ; Gupta et al, 2020 ). However, it has been demonstrated that mixing enantiomers can change the kinetics, morphology, and mechanical properties of peptide self-assemblies ( Nagy-Smith et al, 2017 ; McAulay et al, 2019 ; Bera et al, 2020 ; Qin et al, 2021 ). For example, the racemic mixture of Fmoc monosubstituted cyclo-(EE) and its D -analog formed quickly recoverable thixotropic hydrogel with a significantly shortened thixotropic recovery time compared with the hydrogels formed by either enantiomer alone ( Wang L. et al, 2017 ).…”

Inversion of Supramolecular Chirality by In Situ Hydrolyzation of Achiral Diethylene Glycol Motifs

“…The side-chain substituent of building unit is closely related to the assembly morphology due to the effect of side-chain interaction on molecular stacking. , For example, the amino acid substitution has been found to be involved with the handedness of helical aggregates. − The chirality of amino acids determines twist orientation of chiral structures via transformation of molecular chirality into a microscopic spiral . Besides chiral substituents, introduction of achiral motifs (e.g., oligo­(ethylene glycol)) can also trigger chirality inversion of helical nanostructures via altering stacking mode of the assembled building molecules .…”

Chirality, Gelation Ability and Crystal Structure: Together or Apart? Alkyl Phenyl Ethers of Glycerol as Simple LMWGs

“…While many of them form gels (not always identical in characteristics) regardless of the enantiomeric composition, relatively simple compounds of this class exhibited their specific properties only in the enantiopure form and did not exhibit in the racemic form, and vice versa. Examples of such behavior are given in reviews [22,23] and this effect has also been noted in recent publications [24][25][26][27]. Subsequently, this minor mystery of chiral gels was obscured by other, significant in meaning and spectacular in illustrations, problems of supramolecular chirality [28,29] and chiral recognition [30], which are clearly manifested in nanostructured media.…”