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.

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.

Single-handed supramolecular double helix of homochiral bis(N-amidothiourea) supported by double crossed C-I···S halogen bonds.

The natural DNA double helix consists of two strands of nucleotides that are held together by multiple hydrogen bonds. Here we propose to build an artificial double helix from fragments of two strands connected by covalent linkages therein, but with halogen bonding as the driving force for self-assembling the fragments to the double helix. We succeed in building such a double helix in both solution and solid state, by using a bilateral N-(p-iodobenzoyl)alanine based amidothiourea which in its folded cis-form allows double and crossed C-I···S halogen bonds that lead to right- or left-handed double helix when the two alanine residues are of the same L,L- or D,D-configuration. The double helix forms in dilute CH3CN solution of the micromolar concentration level, e.g., 5.6 µM from 2D NOESY experiments and exhibits a high thermal stability in solution up to 75 °C, suggesting cooperative and thereby strong intermolecular double crossed halogen bonding that makes the double helix stable. This is supported by the observed homochiral self-sorting in solution.

Proline-Based Boronic Acid Receptors for Chiral Recognition of Glucose.

Chiral recognition remains a major challenge in the area of molecular receptor design. With this research, we set out to explore the use of proline-based receptors for chiral recognition. Importantly, the proline structure allows for the introduction of at least two different binding groups due to the availability of both an amine and carboxylic acid group. Here we report a proof-of-concept exploration into the chiral recognition of d/l-glucose as a model chiral species, which prefers to bind to at least two boronic acid groups. We evaluated several proline-based receptors incorporating two phenylboronic acid groups, respectively, at the N- and C-termini of the amino acid residue, via amide bonds. We confirmed that the receptors exhibited chiral recognition using CD, 1H NMR, and 19F NMR spectroscopy. Given the derivation diversity available, our strategy to use proline-based receptors for chiral recognition holds significant promise for extension to other chiral systems.

Short Azapeptides of Folded Structures in Aqueous Solutions.

Building folded short peptides that are driven by the intramolecular hydrogen bonding in aqueous solutions remains challenging because of their highly competitive intermolecular hydrogen-bonding interactions with water solvent molecules that would have favored the extended conformations. Here, we show folded ß-turn structures in acyl amino acid-based N-amidothioureas, the nonclassic azapeptides, in aqueous solutions, as well as in solid-state and organic solvents, by X-ray crystal structures, DFT calculations, 1D and 2D NMR spectra, and absorption and CD spectra. The achiral phenylthiourea chromophore acts as a CD reporter for the ß-turn structure that communicates the chirality of the amino acid residue to the achiral thiourea moiety and the relative intensity of the intramolecular hydrogen bond that stabilizes the turn structure. The amidothiourea moiety represents a versatile structural framework for folded short peptides in aqueous environments.

Folded short azapeptide for conformation switching-based fluorescence sensing.

Herein, we report a conformation switching-based fluorescence sensing scheme using dipeptide-based amidothioureas (azapeptides) that contain a folded ß-turn structure. Amidothiourea is equipped at its two termini with an electron acceptor and an electron donor or two fluorophores, such that it exhibits enhanced exciplex or excimer emission because of the turn structure in which the two termini are brought into close proximity; on the other hand, it exhibits a dramatic ratiometric fluorescence response upon anion binding to the thiourea moiety because of the resultant extended conformation of the anion binding complex.

C-I···π Halogen Bonding Driven Supramolecular Helix of Bilateral N-Amidothioureas Bearing ß-Turns.

We report the first example of C-I···π halogen bonding driven supramolecular helix in highly dilute solution of micromolar concentration, using alanine based bilateral I-substituted N-amidothioureas that contain helical fragments, the ß-turn structures. The halogen bonding interactions afford head-to-tail linkages that help to propagate the helicity of the helical fragments. In support of this action of the halogen bonding, chiral amplification was observed in the supramolecular helix formed in acetonitrile solution. The present finding provides alternative tools in the design of self-assembling macromolecules.