Noncovalent interaction network of chalcogen, halogen and hydrogen bonds for supramolecular ß-sheet organization.

An alanine-based bilateral building block, linked by 2,5-thiophenediamide motifs and equipped with C-terminal 4-iodoaniline groups, was designed, allowing a noncovalent interaction network consisting of intramolecular chalcogen bonds and intermolecular halogen/hydrogen bonds, which cooperatively maintain a supramolecular ß-sheet organization in the solid state, as well as in dilute CH3CN solution with a high g factor of -0.017.

Spontaneous Resolution of Helical Building Blocks through the Formation of Homochiral Helices in Two Dimensions.

Spontaneous resolution leading to conglomerate crystals remains a significant challenge. Here we propose the formation of orthogonal homochiral supramolecular helices in at least two dimensions to allow spontaneous resolution. We suggest the design rationale that the chiral species is made into helical building blocks to allow the helix formation. As a proof-of-concept, acetylalanine was made into a helical short azapeptide, its N-amidothiourea derivative containing a ß-turn structure, to which a halogen atom was further introduced at the phenylthiourea aromatic ring. The resultant folded species undergoes both intermolecular hydrogen and halogen bonding across the turn structure to form orthogonal intermolecular hydrogen-bonded and halogen-bonded supramolecular helices in two dimensions, and undergoes chiral resolution upon crystallization. Meanwhile, counterparts containing either an F-substituent with weak halogen bonding or no halogen atom crystallize as racemic compounds.

Intramolecular chalcogen bonding to tune the molecular conformation of helical building blocks for a supramolecular helix.

We propose to employ intramolecular chalcogen bonding to make a helical building block take its otherwise unfavorable cis-conformation. The 2,5-thiophenediamide motif was taken to bridge two ß-turn structures to lead to an azapeptide that exists in cis-conformation and forms a halogen-bonded single-strand helix that exhibits a much stronger supramolecular helicity and a higher thermal stability.

Supramolecular helices from helical building blocks via head-to-tail intermolecular interactions.

Supramolecular helices from helical building blocks represent an emerging analogue of the α-helix. In cases where the helicity of the helical building block is well propagated, the head-to-tail intermolecular interactions that lead to the helix could be enhanced to promote the formation and the stability of the supramolecular helix, wherein homochiral elongation dominates and functional helical channel structures could also be generated. This feature article outlines the supramolecular helices built from helical building blocks, i.e., helical aromatic foldamers and helical short peptides that are held together by intermolecular π-π stacking, hydrogen/halogen/chalcogen bonding, metal coordination, dynamic covalent bonding and solvophobic interactions, with emphasis on the influence of efficient propagation of helicity during assembly, favouring homochirality and channel functions.

Chalcogen bonding mediates the formation of supramolecular helices of azapeptides in crystals.

To explore whether chalcogen bonding was able to drive the formation of supramolecular helices, alanine-based azapeptides containing a ß-turn structure, with a thiophene group, respectively, incorporated in the N- or C-terminus, were employed as helical building blocks. While the former derivative formed a supramolecular M-helix via intermolecular SS chalcogen bonding in crystals, the latter formed P-helix via intermolecular SO chalcogen bonding.

Solvophobic interaction promoted supramolecular helical assembly of building blocks of weak intermolecular halogen bonding.

We report supramolecular helical assembly in water of ß-turn structured bis(N-amidothioureas) containing Br-substitutes of moderate halogen bonding ability, promoted by stronger hydrophobic interaction. The helical polymers show an unusual negative nonlinear CD-ee dependence.

Turn Conformation of ß-Amino Acid-Based Short Peptides Promoted by an Amidothiourea Moiety at C-Terminus.

A C-terminal amidothiourea motif is shown to promote a ß-turn-like folded conformation in a series of ß-amino acid-based short peptides in both the solid state and solution phase by an intramolecular 11-membered ring hydrogen bond.

Transmembrane Fluoride Transport by a Cyclic Azapeptide With Two ß-Turns.

Diverse classes of anion transporters have been developed, most of which focus on the transmembrane chloride transport due to its significance in living systems. Fluoride transport has, to some extent, been overlooked despite the importance of fluoride channels in bacterial survival. Here, we report the design and synthesis of a cyclic azapeptide (a peptide-based N-amidothiourea, 1), as a transporter for fluoride transportation through a confined cavity that encapsulates fluoride, together with acyclic control compounds, the analogs 2 and 3. Cyclic receptor 1 exhibits more stable ß-turn structures than the control compounds 2 and 3 and affords a confined cavity containing multiple inner -NH protons that serve as hydrogen bond donors to bind anions. It is noteworthy that the cyclic receptor 1 shows the capacity to selectively transport fluoride across a lipid bilayer on the basis of the osmotic and fluoride ion-selective electrode (ISE) assays, during which an electrogenic anion transport mechanism is found operative, whereas no transmembrane transport activity was found with 2 and 3, despite the fact that 2 and 3 are also able to bind fluoride via the thiourea moieties. These results demonstrate that the encapsulation of an anionic guest within a cyclic host compound is key to enhancing the anion transport activity and selectivity.