Pnictogen bonding in imide derivatives for chiral folding and self-assembly.

Pnictogen bonding (PnB) is an attraction interaction that originates from the anisotropic distribution of electron density of pnictogen elements, which however has been rarely found in nitrogen atoms. In this work, for the first time, we unveil the general presence of N-involved PnB in aromatic or aliphatic imide groups and reveal its implications in chiral self-assembly of folding. This long-neglected interaction was consolidated by Cambridge structural database (CSD) searching as well as subsequent computational studies. Though the presence of PnB has limited effects on spectroscopic properties in the solution phase, conformation locking effects are sufficiently expressed in the chiral folding and self-assembly behavior. PnB anchors the chiral conformation to control the emergence and inversion of chiroptical signals, while intramolecular PnB induces the formation of supramolecular tilt chirality. It also enables the chiral folding of imide-containing amino acid or peptide derivatives, which induces the formation of unique secondary structural sequences such as ß-sheets. Finally, the effects of PnB in directing folded helical structures were revealed. Examples of cysteine and cystine derivatives containing multiple N⋯O and N⋯S PnBs constitute an α-helix like secondary structure with characteristic circular dichroism. This work discloses the comprehensive existence of imide-involved PnB, illustrates its important role in folding and self-assembly, and sheds light on the rational fabrication of conformation-locked compounds and polymers with controllable chiroptical activities.

Ultrasensitive Solvatochirochromism of Single Benzene Chromophores.

Solvents influence the structure, aggregation and folding behaviors of solvatochromic compounds. Ultrasensitive solvent mediated chiroptical response is conducive to the fabrication of molecular platform for sensing and recognition, which however, remains great challenges in conceptual or applicable design. Here we report a cysteine-based single benzene chromophore system that shows ultrasensitivity to solvents. Compared to the ratiometrically responsive systems, the chiroptical activities could be triggered or inverted depending on the substituents of chiral entities with an ultralow solvent volume fraction (<1 vol %). One drop of dipolar solvents shall significantly induce the emergence or inversion of chiroptical signals in bulky phases. Based on the experimental and computational studies, the ultrasensitivity is contributed to the intimate interplay between solvents and chiral compounds that anchors the specific chiral conformation. It illustrates that structurally simple organic compounds without aggregation or folding behaviors possess pronounced solvatochiroptical properties, which sheds light on the next-generation of chiroptical sensors and switches.

Four-Component Ugi Reaction for Optical Chirality Sensing and Surface Nanoengineering of Chiral Self-Assemblies.

Using green chemistry to control chirality at hierarchical levels as well as chiroptical activities endows with new opportunities to the development of multiple functions. Here, the four-component Ugi reaction is introduced for the general and precise optical chirality sensing of amines as well as the surface nanoengineering of chiral soft self-assemblies. To overcome the relatively weak Cotton effects, direct synthesis of a folded peptide structure on a rotatable ferrocene core with axial chirality was accomplished from chiral amine, 1,1'-ferrocenyl dicarboxylic acid, formaldehyde and isocyanide. Enhanced Cotton effects benefiting from the folded structure allow for the precise and quantitative sensing of natural and synthetic chiral amines covering alkyl, aromatic amines and amino acid derivatives. In addition, aqueous reaction enables the modification of amine-bearing dye to microfibers self-assembled from π-conjugated amino acids. Surface dye-modification via Ugi reaction barely changes the pristine morphology, showing non-invasive properties in contrast to dye staining, which is applicable in soft nano/microarchitectures from self-assembly. This work which combines the four-component Ugi reaction to enable precise ee% detection and surface nanoengineering of soft chiral assemblies sheds light on the advanced application of green chemistry to chirality science.

Supramolecular secondary helical structures in solid-state N-protected amino acids.

Helix is an important secondary structure in proteins and polypeptides, which, however, has rarely been recognized in amino acids or their simple derivatives. In this work, we firstly unveil the generic existence of supramolecular helical secondary structures in solid-state N-protected amino acids. Throughout searching in Cambridge Structural Database followed by screening, ∼10% N-protected amino acids were evidenced to form H-bonded helical structures, thus covering 15 coded amino acids and diverse types of protecting groups. Helical structures were typically classified as 21 and 31 symmetry, and specific double-strand helical structures were discovered. Computational studies on the calculated electronic circular dichroism spectra show well-defined correlation to experimental results, indicative of the supramolecular secondary structures that possess feature Cotton effects similar to naturally occurring α-helices in proteins. Such feature Cotton effects could be transferred to protecting groups, which is of vital significance to the emerging chiroptical materials. This work highlighting the neglected structural analysis would offer a better understanding and deep insight into the structure relationship on the supramolecular chiral materials, crystal engineering and chiroptical materials based on amino acids and their derivatives.

A supramolecular vesicle of camptothecin for its water dispersion and controllable releasing.

Camptothecin, as an antitumor drug, has shown significant antitumor activity against various cancers through the inhibition of topoisomerase I. However, its poor solubility severely limits the clinical applications. Here, we report a camptothecin supramolecular vesicle based on the host-guest interactions, which can uniformly disperse camptothecin into water and greatly enhance camptothecin aqueous solubility. The camptothecin vesicles were identified by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS). X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV-vis spectrum, 1H NMR and 2D NMR ROESY were further employed to study the formation mechanism of the vesicles. Furthermore, camptothecin could be controllably released when the competitive guests were added into the vesicles system. Finally, the camptothecin vesicles in aqueous solution exhibited comparable antitumor activity in vitro as natural camptothecin in DMSO to HeLa cells under the same conditions.

Strategy of directly employing paclitaxel to construct vesicles.

A class of aza-arm modified ß-cyclodextrins were found to be able to trap paclitaxel (PTX), an effective but strongly hydrophobic anticancer drug, to form novel "supramolecular amphiphiles", which can further self-assemble into vesicular structures in aqueous solution. The obtained vesicles were characterized in detail by transmission electron microscopy (TEM), scanning electron microscopy (SEM), cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The mechanism of the vesicular formation was suggested on the basis of the experimental results of nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermal analysis. The effects to the vesicular formation by changing the host molecules and solvents were also studied. The vesicles will disappear upon the introduction of Cu(2+) into the vesicular system, during the procedure of which, PTX will be released meanwhile. We believe that our research will provide a new strategy of directly employing special drugs to construct microvehicles to carry other targeted molecules.

Self-assembled vesicles prepared from amphiphilic cyclodextrins as drug carriers.

Controlled self-assembly of amphiphilic cyclodextrin is always a challenging topic in the field of supramolecular chemistry, since it provides the spontaneous generation of well-defined aggregation with functional host sites with great potential applications in drug-carrier systems. ß-Cyclodextrin modified with an anthraquinone moiety (1) was successfully synthesized. In the aqueous solution, 1 was found able to self-assemble into vesicles, which was characterized in detail by TEM, SEM, EFM, and DLS. The formation mechanism of the vesicles was suggested based on the 2D ROESY and UV-vis results, and further verified by the MD simulation. Subsequently, the stimuli response property of the vesicles, including to Cu(2+) and H(+), was also studied. The vesicles can efficiently load Paclitaxel inside the membrane with functional macrocyclic cavities available, which can further carry small molecules, such as ferrocene. The vesicles loading with Paclitaxel have remarkable anticancer effects. This work will provide new strategy in drug-carrier systems and tumor treatment methods.