DNA Nanoribbon‐Templated Self‐Assembly of Ultrasmall Fluorescent Copper Nanoclusters with Enhanced Luminescence

Fluorescent copper nanoclusters (CuNCs) have been widely used in chemical sensors, biological imaging, and light‐emitting devices. However, individual fluorescent CuNCs have limitations in their capabilities arising from poor photostability and weak emission intensities. As one kind of aggregation‐induced emission luminogen (AIEgen), the formation of aggregates with high compactness and good order can efficiently improve the emission intensity, stability, and tunability of CuNCs. Here, DNA nanoribbons, containing multiple specific binding sites, serve as a template for in situ synthesis and assembly of ultrasmall CuNCs (0.6 nm). These CuNC self‐assemblies exhibit enhanced luminescence and excellent fluorescence stability because of tight and ordered arrangement through DNA nanoribbons templating. Furthermore, the stable and bright CuNC assemblies are demonstrated in the high‐sensitivity detection and intracellular fluorescence imaging of biothiols.     

A Molecular Dynamics Study on Controlling the Self‐Assembly of β‐Sheet Peptides with Designer Nanorings

Recently, a rational approach for constructing β‐barrel protein mimics by the self‐assembly of peptide‐based building blocks has been demonstrated. We performed molecular dynamics simulations of nanoring formation by means of the self‐assembly of designed β‐sheet‐forming peptides. Several factors contributing to the stability of the nanoring structures with respect to size were investigated. Our simulations predicted that an optimal nanoring size may be achieved by minimizing repulsions due to steric hindrance between bulky groups while maintaining favorable hydrogen‐bond interactions between neighboring β‐sheet chains. It was shown that mutations in a test peptide, in which all or half of the tryptophan residues were replaced by phenylalanine, could enable the assembly of stable nanoring structures with smaller pore sizes. Insights into the fundamental factors driving the formation of peptide‐based nanostructures are expected to facilitate the design of novel functional bionanostructures.     

Short Self‐Assembling Peptides Are Able to Bind to Copper and Activate Oxygen

We have shown that de novo designed peptides self‐assemble in the presence of copper to create supramolecular assemblies capable of carrying out the oxidation of dimethoxyphenol in the presence of dioxygen. Formation of the supramolecular assembly, which is akin to a protein fold, is critical for productive catalysis since peptides possessing the same functional groups but lacking the ability to self‐assemble do not catalyze substrate oxidation. The ease with which we have discovered robust and productive oxygen activation catalysts suggests that these prion‐like assemblies might have served as intermediates in the evolution of enzymatic function and opens the path for the development of new catalyst nanomaterials.     

Self‐Assembled Cyclic Structures from Copper(II) Peptoids

Metal–ligand coordination is a key interaction in the self‐assembly of both biopolymers and synthetic oligomers. Although the binding of metal ions to synthetic proteins and peptides is known to yield high‐order structures, the self‐assembly of peptidomimetic molecules upon metal binding is still challenging. Herein we explore the self‐assembly of three peptoid trimers bearing a bipyridine ligand at their C‐terminus, a benzyl group at their N‐terminus, and a polar group (N‐ethyl‐R) in the middle position (R=OH, OCH₃, or NH₂) upon Cu²⁺ coordination. X‐ray diffraction analysis revealed unique, highly symmetric, dinuclear cyclic structure or aqua‐bridged dinuclear double‐stranded peptoid helicates, formed by the self‐assembly of two peptoid molecules with two Cu²⁺ ions. Only the macrocycle with the highest number of intermolecular hydrogen bonds is stable in solution, while the other two disassemble to their corresponding monometallic complexes.     

Engineering the Ionic Self‐Assembly of Polyoxometalates and Facial‐Like Peptides

The self‐assembly behavior of polyoxometalates (PMs) and facial‐like cationic peptides carrying lysine residues were systematically investigated. Circular dichroism and UV/Vis spectra demonstrated that the multivalent electrostatic attractions between polyanionic PMs and short peptides with protonated lysine residues initiated the conformational transition of peptide molecules from random‐coil to β‐sheet state, and subsequently the co‐assembly. TEM and atomic force microscopy (AFM) measurements showed that uniform nanofibers formed with decreasing size of the PMs or increasing the intermolecular forces of the peptides, such as through hydrogen‐bonding, hydrophobic, and/or π–π interactions. Additionally, the stability of the nanostructures can be improved by rational suppression of the electrostatic repulsion of the shell peptides covering the surface of the nanostructures. These results provide new insight into understanding the ionic self‐assembly of peptides and PMs and controlling their final morphology.     

Spontaneous Nanobelt Formation by Self‐Assembly of β‐Benzyl GABA

We present the formation of a nanobelt by self‐assembly of β‐benzyl GABA (γ‐aminobutyric acid). This simple γ‐amino acid building block self‐assembled to form a well‐defined nanobelt in chloroform. The nanobelt showed distinct optical properties due to π–π interactions. This new‐generation self‐assembled single amino acid may serve as a template for functional nanomaterials.     

Enzymatic Control of the Conformational Landscape of Self‐Assembling Peptides

Post‐translational modification is a common mechanism to affect conformational change in proteins, which in turn, regulates function. Herein, this principle is expanded to instruct the formation of supramolecular assemblies by controlling the conformational bias of self‐assembling peptides. Biophysical and mechanical studies show that an engineered phosphorylation/dephosphorylation couple can affectively modulate the folding of amphiphilic peptides into a conformation necessary for the formation of well‐defined fibrillar networks. Negative design principles based on the incompatibility of hosting residue side‐chain point charge within hydrophobic environments proved key to inhibiting the peptide's ability to adopt its low energy fold in the assembled state. Dephosphorylation relieves this restriction, lowers the energy barrier between unfolded and folded peptide, and allows the formation of self‐assembled fibrils that contain the folded conformer, thus ultimately enabling the formation of a cytocompatible hydrogel material.     

Tuning One‐Dimensional Nanostructures of Bola‐Like Peptide Amphiphiles by Varying the Hydrophilic Amino Acids

By combining experimental measurements and computer simulations, we here show that for the bola‐like peptide amphiphiles XI₄X, where X=K, R, and H, the hydrophilic amino acid substitutions have little effect on the β‐sheet hydrogen‐bonding between peptide backbones. Whereas all of the peptides self‐assemble into one dimensional (1D) nanostructures with completely different morphologies, that is, nanotubes and helical nanoribbons for KI₄K, flat and multilayered nanoribbons for HI₄H, and twisted and bilayered nanoribbons for RI₄R. These different 1D morphologies can be explained by the distinct stacking degrees and modes of the three peptide β‐sheets along the x‐direction (width) and the z‐direction (height), which microscopically originate from the hydrogen‐bonding ability of the sheets to solvent molecules and the pairing of hydrophilic amino acid side chains between β‐sheet monolayers through stacking interactions and hydrogen bonding. These different 1D nanostructures have distinct surface chemistry and functions, with great potential in various applications exploiting the respective properties of these hydrophilic amino acids.     

Copper(I)‐Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β‐Tetrapeptide Analogues

A copper(I)‐mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β‐amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α₃β‐tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)‐catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α₃β‐tetrapeptide framework have been successfully synthesized.     

Polyoxometalate‐Driven Self‐Assembly of Short Peptides into Multivalent Nanofibers with Enhanced Antibacterial Activity

Multivalent peptide nanofibers have attracted intense attention as promising platforms, but the fabrication of those nanofibers is mainly dependent on the spontaneous assembly of β‐sheet peptides. Herein we report an alternative approach to the creation of nanofibers: the polyoxometalate‐driven self‐assembly of short peptides. The resultant nanofibers with concentrated positive charges are excellent multivalent ligands for binding with bacterial cells and thus lead to a salient improvement in bioactivity.     

Colloidal Self‐Assembly of Catalytic Copper Nanoclusters into Ultrathin Ribbons

Metal nanoclusters (NCs) with diameter below 2 nm are promising catalysts in oxygen reduction reactions (ORR). However, the high surface energy of ultra‐small clusters leads to structural instability, shedding doubt on practical applications. Herein, we demonstrate a self‐assembly method to improve the durability of catalytic metal NCs, employing copper NCs capped by 1‐dodecanethiol (DT) to form free‐standing ribbons in colloidal solution. By tuning the cooperation between the dipolar attraction between Cu NCs and the van der Waals attraction between DT, the thickness of ribbons is adjusted to a single NC scale. Such free‐standing ribbons exhibit excellent catalytic activity and durability in ORR.     

Isomerization‐ and Temperature‐Jump‐Induced Dynamics of a Photoswitchable β‐Hairpin

Conformational changes in proteins and peptides can be initiated by diverse processes. This raises the question how the variation of initiation mechanisms is connected to differences in folding or unfolding processes. In this work structural dynamics of a photoswitchable β‐hairpin model peptide were initiated by two different mechanisms: temperature jump (T‐jump) and isomerization of a backbone element. In both experiments the structural changes were followed by time‐resolved IR spectroscopy in the nanosecond to microsecond range. When the photoisomerization of the azobenzene backbone switch initiated the folding reaction, pronounced absorption changes related to folding into the hairpin structure were found with a time constant of about 16 μs. In the T‐jump experiment kinetics with the same time constant were observed. For both initiation processes the reaction dynamics revealed the same strong dependence of the reaction time on temperature. The highly similar transients in the microsecond range show that the peptide dynamics induced by T‐jump and isomerization are both determined by the same mechanism and exclude a downhill‐folding process. Furthermore, the combination of the two techniques allows a detailed model for folding and unfolding to be presented: The isomerization‐induced folding process ends in a transition‐state reaction scheme, in which a high energetic barrier of 48 kJ mol^?1 separates unfolded and folded structures.     

Stabilization of an α Helix by β‐Sheet‐Mediated Self‐Assembly of a Macrocyclic Peptide

Protein roll call : Peptide‐based building blocks, in which both an α‐helix‐forming segment and a β‐sheet segment are located within a single macrocyclic structure, self‐assemble into α‐helix‐decorated artificial proteins. This approach provides a starting point for developing artificial proteins that can modulate α‐helix‐mediated interactions occurring in a multivalent fashion.

     

Programmable Self‐Assembly of Heterometallic Palladium(II)–Copper(II) 1D Grid‐Chain using Dinuclear Palladium(II) Corners with Pyrazole–Carboxylic Acid Ligands

A novel heterometallic diPd^II–diCu^II grid‐chain, {[(bpy)₄Pd₄Cu₂L₄](NO₃)₄}_n ( 2 ; bpy=2,2′‐bipyridine), was synthesized through a programmable self‐assembly approach from the molecular corners [(bpy)₂Pd₂(HL)(L)](NO₃) ( 1 ) as linkers with Cu^II nitrate by using the bifunctional H₂L ligand featuring primary (pyrazole) and secondary (benzoic acid) groups. Structural analysis revealed that 1D structure 2 consists of one [Cu₂(O₂CPh)₄]_n unit as a bridge and two [(bpy)₂Pd₂L₂]_n corners. Additionally, the catalytic effect of the heterometallic synergy on the Suzuki coupling reaction by using 2 was further explored.     

Flow‐Enabled Self‐Assembly of Large‐Scale Aligned Nanowires

One‐dimensional nanowires enable the realization of optical and electronic nanodevices that may find applications in energy conversion and storage systems. Herein, large‐scale aligned DNA nanowires were crafted by flow‐enabled self‐assembly (FESA). The highly oriented and continuous DNA nanowires were then capitalized on either as a template to form metallic nanowires by exposing DNA nanowires that had been preloaded with metal salts to an oxygen plasma or as a scaffold to direct the positioning and alignment of metal nanoparticles and nanorods. The FESA strategy is simple and easy to implement and thus a promising new method for the low‐cost synthesis of large‐scale one‐dimensional nanostructures for nanodevices.     

Surface‐Assisted Self‐Assembly Strategies Leading to Supramolecular Hydrogels

Localized molecular self‐assembly processes leading to the growth of nanostructures exclusively from the surface of a material is one of the great challenges in surface chemistry. In the last decade, several works have been reported on the ability of modified or unmodified surfaces to manage the self‐assembly of low‐molecular‐weight hydrogelators (LMWH) resulting in localized supramolecular hydrogel coatings mainly based on nanofiber architectures. This Minireview highlights all strategies that have emerged recently to initiate and localize LMWH supramolecular hydrogel formation, their related fundamental issues and applications.     

Universal pH‐Responsive and Metal‐Ion‐Free Self‐Assembly of DNA Nanostructures

pH‐responsiveness has been widely pursued in dynamic DNA nanotechnology, owing to its potential in biosensing, controlled release, and nanomachinery. pH‐triggering systems mostly depend on specific designs of DNA sequences. However, sequence‐independent regulation could provide a more general tool to achieve pH‐responsive DNA assembly, which has yet to be developed. Herein, we propose a mechanism for dynamic DNA assembly by utilizing ethylenediamine (EN) as a reversibly chargeable (via protonation) molecule to overcome electrostatic repulsions. This strategy provides a universal pH‐responsivity for DNA assembly since the regulation originates from externally co‐existing EN rather than specific DNA sequences. Furthermore, it endows structural DNA nanotechnology with the benefits of a metal‐ion‐free environment including nuclease resistance. The concept could in principle be expanded to other organic molecules which may bring unique controls to dynamic DNA assembly.