Template‐Free Supracolloidal Self‐Assembly of Atomically Precise Gold Nanoclusters: From 2D Colloidal Crystals to Spherical Capsids

We report supracolloidal self‐assembly of atomically precise and strictly monodisperse gold nanoclusters involving p‐mercaptobenzoic acid ligands (Au₁₀₂‐pMBA₄₄) under aqueous conditions into hexagonally packed monolayer‐thick two‐dimensional facetted colloidal crystals (thickness 2.7 nm) and their bending to closed shells leading to spherical capsids (d ca. 200 nm), as controlled by solvent conditions. The 2D colloidal assembly is driven in template‐free manner by the spontaneous patchiness of the pMBA ligands around the Au₁₀₂‐pMBA₄₄ nanoclusters preferably towards equatorial plane, thus promoting inter‐nanocluster hydrogen bonds and high packing to planar sheets. More generally, the findings encourage to explore atomically precise nanoclusters towards highly controlled colloidal self‐assemblies.     

Dynamic Self‐Assembly of Gold/Polymer Nanocomposites: pH‐Encoded Switching between 1D Nanowires and 3D Nanosponges

The design of tunable dynamic self‐assembly of nanoparticles with switchable assembled dimensions and morphologies is a challenging goal whose realization is vital for the evolution of smart nanomaterials. Herein, we report on chitosan polymer as an effective supramolecular “glue” for aldehyde‐modified Au nanoparticles to reversibly modulate the states of self‐assembled nanocomposites. By simultaneous integration of dynamic covalent Schiff base interactions and noncovalent hydrogen bonds, the chitosan/Au nanocomposites could reversibly transform their assembled morphologies from one‐dimensional nanowires to three‐dimensional nanosponges in response to the variation of pH value. Moreover, the obtained nanosponges could be used as an efficient pH‐controlled cargo release system.     

Enantiomeric and Diastereomeric Self‐Assembled Multivalent Nanostructures: Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA

A family of four self‐assembling lipopeptides containing Ala‐Lys peptides attached to a C₁₆ aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C₁₆‐l ‐Ala‐l ‐Lys/C₁₆‐d ‐Ala‐d ‐Lys) and (C₁₆‐d ‐Ala‐l ‐Lys/C₁₆‐l ‐Ala‐d ‐Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self‐assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d ‐lysine ligands, with a further slight preference for attachment to l ‐alanine, with the CMC being irrelevant.     

Host–Guest Binding‐Site‐Tunable Self‐Assembly of Stimuli‐Responsive Supramolecular Polymers

Despite the remarkable progress made in controllable self‐assembly of stimuli‐responsive supramolecular polymers (SSPs), a basic issue that has not been consideration to date is the essential binding site. The noncovalent binding sites, which connect the building blocks and endow supramolecular polymers with their ability to respond to stimuli, are expected to strongly affect the self‐assembly of SSPs. Herein, the design and synthesis of a dual‐stimuli thermo‐ and photoresponsive Y‐shaped supramolecular polymer (SSP2) with two adjacent β‐cyclodextrin/azobenzene (β‐CD/Azo) binding sites, and another SSP (SSP1) with similar building blocks, but only one β‐CD/Azo binding site as a control, are described. Upon gradually increasing the polymer solution temperature or irradiating with UV light, SSP2 self‐assemblies with a higher binding‐site distribution density; exhibits a flower‐like morphology, smaller size, and more stable dynamic aggregation process; and greater controllability for drug‐release behavior than those observed with SSP1 self‐assemblies. The host–guest binding‐site‐tunable self‐assembly was attributed to the positive cooperativity generated among adjacent binding sites on the surfaces of SSP2 self‐assemblies. This work is beneficial for precisely controlling the structural parameters and controlled release function of SSP self‐assemblies.     

Complexing DNA Origami Frameworks through Sequential Self‐Assembly Based on Directed Docking

Ordered DNA origami arrays have the potential to compartmentalize space into distinct periodic domains that can incorporate a variety of nanoscale objects. Herein, we used the cavities of a preassembled 2D DNA origami framework to incorporate square‐shaped DNA origami structures (SQ‐origamis). The framework was self‐assembled on a lipid bilayer membrane from cross‐shaped DNA origami structures (CR‐origamis) and subsequently exposed to the SQ‐origamis. High‐speed AFM revealed the dynamic adsorption/desorption behavior of the SQ‐origamis, which resulted in continuous changing of their arrangements in the framework. These dynamic SQ‐origamis were trapped in the cavities by increasing the Mg²⁺ concentration or by introducing sticky‐ended cohesions between extended staples, both from the SQ‐ and CR‐origamis, which enabled the directed docking of the SQ‐origamis. Our study offers a platform to create supramolecular structures or systems consisting of multiple DNA origami components.     

Hierarchical Self‐Assembly of Poly‐Pseudorotaxanes into Artificial Microtubules

Hierarchical self‐assembly of building blocks over multiple length scales is ubiquitous in living organisms. Microtubules are one of the principal cellular components formed by hierarchical self‐assembly of nanometer‐sized tubulin heterodimers into protofilaments, which then associate to form micron‐length‐scale, multi‐stranded tubes. This peculiar biological process is now mimicked with a fully synthetic molecule, which forms a 1:1 host‐guest complex with cucurbit[7]uril as a globular building block, and then polymerizes into linear poly‐pseudorotaxanes that associate laterally with each other in a self‐shape‐complementary manner to form a tubular structure with a length over tens of micrometers. Molecular dynamic simulations suggest that the tubular assembly consists of eight poly‐pseudorotaxanes that wind together to form a 4.5 nm wide multi‐stranded tubule.     

Tunable Self‐Assembly of Triazole‐Linked Porphyrin–Polymer Conjugates

The convergence of supramolecular chemistry and polymer science offers many powerful approaches for building functional nanostructures with well‐defined dynamic behaviour. Herein we report the efficient “click” synthesis and self‐assembly of AB₂‐ and AB₄‐type multitopic porphyrin–polymer conjugates (PPCs). PPCs were prepared using the copper(I)‐catalysed azide–alkyne cycloaddition (CuAAC) reaction, and consisted of linear polystyrene, poly(butyl acrylate), or poly(tert‐butyl acrylate) arms attached to a zinc(II) porphyrin core via triazole linkages. We exploit the presence of the triazole groups obtained from CuAAC coupling to direct the self‐assembly of the PPCs into short oligomers (2–6 units in length) via intermolecular porphyrinatozinc–triazole coordination. By altering the length and grafting density of the polymer arms, we demonstrate that the association constant of the porphyrinatozinc–triazole complex can be systematically tuned over two orders of magnitude. Self‐assembly of the PPCs also resulted in a 6 K increase in the glass transition temperature of the bulk material compared to a non‐assembling PPC. The modular synthesis and tunable self‐assembly of the triazole‐linked PPCs thus represents a powerful supramolecular platform for building functional nanostructured materials.     

Self‐Assembly of Proteins: Towards Supramolecular Materials

The study of protein self‐assembly has attracted great interest over the decades, due to the important role that proteins play in life. In contrast to the major achievements that have been made in the fields of DNA origami, RNA, and synthetic peptides, methods for the design of self‐assembling proteins have progressed more slowly. This Concept article provides a brief overview of studies on native protein and artificial scaffold assemblies and highlights advances in designing self‐assembling proteins. The discussions are focused on design strategies for self‐assembling proteins, including protein fusion, chemical conjugation, supramolecular, and computational‐aided de novo design.     

A Chiral Recognition System Orchestrated by Self‐Assembly: Molecular Chirality,Self‐Assembly Morphology,and Fluorescence Response

The newly developed oligophenylenevinylene (OPV)‐based fluorescent (FL) chiral chemosensor (OPV‐Me) for the representative enantiomeric guest, 1,2‐cyclohexanedicarboxylic acid (1,2‐CHDA: RR ‐ and SS ‐form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV‐Me self‐assembly: RR ‐CHDA directed the fibrous supramolecular aggregate, whereas SS ‐CHDA directed the finite aggregate. The consequent FL intensity toward RR ‐CHDA was up to 30 times larger than that toward SS ‐CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV‐Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self‐assembly.     

Programmable Assembly of Nano‐architectures through Designing Anisotropic DNA Origami Patches

Programmable assembly of nanoparticles (NPs) into well‐defined architectures has attracted attention because of tailored properties resulting from coupling effects. However, general and precise approaches to control binding modes between NPs remain a challenge owing to the difficulty in manipulating the accurate positions of the functional patches on the surface of NPs. Here, a strategy is developed to encage spherical NPs into pre‐designed octahedral DNA origami frames (DOFs) through DNA base‐pairings. The DOFs logically define the arrangements of functional patches in three dimensions, owing to the programmability of DNA hybridization, and thus control the binding modes of the caged nanoparticle with designed anisotropy. Applying the node‐and‐spacer approach that was widely used in crystal engineering to design coordination polymers, patchy NPs could be rationally designed with lower symmetry encoded to assemble a series of nano‐architectures with high‐order geometries.     

Surface‐Assisted Self‐Assembly of a Hydrogel by Proton Diffusion

Controlling supramolecular growth at solid surfaces is of great importance to expand the scope of supramolecular materials. A dendritic benzene‐1,3,5‐tricarboxamide peptide conjugate is described in which assembly can be triggered by a pH jump. Stopped‐flow kinetics and mathematical modeling provide a quantitative understanding of the nucleation, elongation, and fragmentation behavior in solution. To assemble the molecule at a solid–liquid interface, we use proton diffusion from the bulk. The latter needs to be slower than the lag phase of nucleation to progressively grow a hydrogel outwards from the surface. Our method of surface‐assisted self‐assembly is generally applicable to other gelators, and can be used to create structured supramolecular materials.     

Reversible Guest Uptake/Release by Redox‐Controlled Assembly/Disassembly of a Coordination Cage

Controlling the guest expulsion process from a receptor is of critical importance in various fields. Several coordination cages have been recently designed for this purpose, based on various types of stimuli to induce the guest release. Herein, we report the first example of a redox‐triggered process from a coordination cage. The latter integrates a cavity, the panels of which are based on the extended tetrathiafulvalene unit (exTTF). The unique combination of electronic and conformational features of this framework (i.e. high π‐donating properties and drastic conformational changes upon oxidation) allows the reversible disassembly/reassembly of the redox‐active cavity upon chemical oxidation/reduction, respectively. This cage is able to bind the three‐dimensional B₁₂F₁₂^2? anion in a 1:2 host/guest stoichiometry. The reversible redox‐triggered disassembly of the cage could also be demonstrated in the case of the host–guest complex, offering a new option for guest‐delivering control.     

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.     

Hierarchical Co‐Assembly Enhanced Direct Ink Writing

Integrating intelligent molecular systems into 3D printing materials and transforming their molecular functions to the macroscale with controlled superstructures will unleash great potential for the development of smart materials. Compared to macromolecular 3D printing materials, self‐assembled small‐molecule‐based 3D printing materials are very rare owing to the difficulties of facilitating 3D printability as well as preserving their molecular functions macroscopically. Herein, we report a general approach for the integration of functional small molecules into 3D printing materials for direct ink writing through the introduction of a supramolecular template. A variety of inorganic and organic small‐molecule‐based inks were 3D‐printed, and their superstructures were refined by post‐printing hierarchical co‐assembly. Through spatial and temporal control of individual molecular events from the nano‐ to the macroscale, fine‐tuned macroscale features were successfully installed in the monoliths.     

Coordination‐Driven Self‐Assembly of a Molecular Knot Comprising Sixteen Crossings

Molecular knots have become highly attractive to chemists because of their prospective properties in mimicking biomolecules and machines. Only a few examples of molecular knots from the billions tabulated by mathematicians have been realized and molecular knots with more than eight crossings have not been reported to date. We report here the coordination‐driven [8+8] self‐assembly of a higher‐generation molecular knot comprising as many as sixteen crossings. Its solid‐state X‐ray crystal structure and multinuclear 2D NMR findings confirmed its architecture and topology. The formation of this molecular knot appears to depend on the functionalities and geometries of donor and acceptor in terms of generating appropriate angles and strong π‐π interactions supported by hydrophobic effects. This study shows coordination‐driven self‐assembly offers a powerful potential means of synthesizing more and more complicated molecular knots and of understanding differences between the properties of knotted and unknotted structures.     

Anion Recognition and Induced Self‐Assembly of an α,γ‐Cyclic Peptide To Form Spherical Clusters

A cyclic octapeptide composed of hydroxy‐functionalized γ‐amino acids folds in a “V‐shaped” conformation that allows the selective recognition of anions such as chloride, nitrate, and carbonate. The process involves the simultaneous self‐assembly of six peptide subunits and the recognition of four anions to form a tetrahedral structure, in which the anions are located at the corners of the resulting structure. Each anion is coordinated to three different peptides. The structure was fully characterized by several techniques, including NMR spectroscopy and X‐ray diffraction, and the material was able to facilitate the transmembrane transport of chloride ions.     

Water‐Soluble Pillar[n]arene Mediated Supramolecular Self‐Assembly: Multi‐Dimensional Morphology Controlled by Host Size

We report tunable supramolecular self‐assemblies formed by water‐soluble pillar[n]arenes ( WPn s, n=5–7) and bipyridinium‐azobenzene guests. Nanoscale or microscale morphology of self‐assemblies in water was controlled by the host size of WPn . Supramolecular self‐assemblies could undergo morphology conversion under irradiation with UV light.     

Fluorescent Cross‐Linked Supramolecular Polymer Constructed by Orthogonal Self‐Assembly of Metal–Ligand Coordination and Host–Guest Interaction

A new host molecule consists of four terpyridine groups as the binding sites with zinc(II) ion and a copillar[5]arene incorporated in the center as a spacer to interact with guest molecule was designed and synthesized. Due to the 120 ° angle of the rigid aromatic segment, a cross‐linked dimeric hexagonal supramolecular polymer was therefore generated as the result of the orthogonal self‐assembly of metal–ligand coordination and host–guest interaction. UV/Vis spectroscopy, ¹H NMR spectroscopy, viscosity and dynamic light‐scattering techniques were employed to characterize and understand the cross‐linking process with the introduction of zinc(II) ion and guest molecule. More importantly, well‐defined morphology of the self‐assembled supramolecular structure can be tuned by altering the adding sequence of the two components, that is, the zinc(II) ion and the guest molecule. In addition, introduction of a competitive ligand suggested the dynamic nature of the supramolecular structure.     

Reciprocal Self‐Assembly of Peptide–DNA Conjugates into a Programmable Sub‐10‐nm Supramolecular Deoxyribonucleoprotein

To overcome the limitations of molecular assemblies, the development of novel supramolecular building blocks and self‐assembly modes is essential to create more sophisticated, complex, and controllable aggregates. The self‐assembly of peptide–DNA conjugates (PDCs), in which two orthogonal self‐assembly modes, that is, β‐sheet formation and Watson–Crick base pairing, are covalently combined in one supramolecular system, is reported. Despite extensive research, most self‐assembly studies have focused on using only one type of building block, which restricts structural and functional diversity compared to multicomponent systems. Multicomponent systems, however, suffer from poor control of self‐assembly behaviors. Covalently conjugated PDC building blocks are shown to assemble into well‐defined and controllable nanostructures. This controllability likely results from the decrease in entropy associated with the restriction of the molecular degrees of freedom by the covalent constraints. Using this strategy, the possibility to thermodynamically program nano‐assemblies to exert gene regulation activity with low cytotoxicity is demonstrated.