Emerging Supramolecular Therapeutic Carriers Based on Host–Guest Interactions

Recent advances in host–guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non‐covalent interactions provide vast possibilities of manipulating supramolecular self‐assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self‐assemblies through host–guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli‐responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co‐delivery and site‐specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host–guest chemistry with biological interface science are proposed.     

De Novo Design of Xeno‐Metallo Coiled Coils

Bioinorganic chemists aspire to achieve the same exquisite and highly controlled inorganic chemistry featured in biology. An exciting mimetic approach involves the use of miniature artificial protein scaffolds designed de novo (often based on the coiled coil (CC) scaffold), for reproducing native metal ion sites and their function. Recently, there is increased interest, instead, in the design of xeno‐metal sites within CC assemblies. This involves incorporating either non‐biological metal ions, cofactors or non‐proteinogenic amino acid ligands for metal ion coordination, whilst retaining a minimal CC protein scaffold. Using this approach, one should be able to create functional designs with unique and unusual properties, which combine the advantages of both biology and ‘traditional’ non‐biological inorganic chemistry. It is the recent progress with respect to the design of xeno‐metallo CCs which will be discussed in this Focus Review.     

卟啉组装体的结构、功能和性质

近年来,卟啉及金属卟啉的超分子化学迅速发展成为现代化学的一个重要分支。卟啉及金属卟啉组装体在光、电、纳米等新型功能材料中有广泛的应用,已引起了人们的极大兴趣。本文就卟啉及金属卟啉组装体的功能、性质及应用前景进行了综述。     

Assemblies of Peptides in a Complex Environment and their Applications

Using peptide assemblies with emergent properties to achieve elaborate functions has attracted increasing attention in recent years. Besides tailoring the self‐assembly of peptides in vitro, peptide research is advancing into a new and exciting frontier: the rational design of peptide assemblies (or their derivatives) for biological functions in a complex environment. This Minireview highlights recent developments in peptide assemblies and their applications in biological systems. After introducing the unique merits of peptide assemblies, we discuss the recent progress in designing peptides (or peptide derivatives) for self‐assembly with conformational control. Then, we describe biological functions of peptide assemblies, with an emphasis on approach‐instructed assembly for spatiotemporal control of peptide assemblies, in the cellular context. Finally, we discuss the future promises and challenges of this exciting area of chemistry.     

Peptide Nanomaterials Designed from Natural Supramolecular Systems

Natural supramolecular assemblies exhibit unique structural and functional properties that have been optimized over the course of evolution. Inspired by these natural systems, various bio‐nanomaterials have been developed using peptides, proteins, and nucleic acids as components. Peptides are attractive building blocks because they enable the important domains of natural protein assemblies to be isolated and optimized while retaining the original structures and functions. Furthermore, the peptide subunits can be conjugated with exogenous molecules such as peptides, proteins, nucleic acids, and metal nanoparticles to generate advanced functions. In this personal account, we summarize recent progress in the construction of peptide‐based nanomaterial designed from natural supramolecular systems, including (1) artificial viral capsids, (2) self‐assembled nanofibers, and (3) protein‐binding motifs. The peptides inspired by nature should provide new design principles for bio‐nanomaterials.     

Reversible Assembly of Microgels by Metallo‐Supramolecular Chemistry

The combination of supramolecular chemistry and soft colloids as microgels represents an ambitious way to develop multi‐versatile colloidal assemblies. Hereafter, terpyridine‐functionalized poly(N‐isopropylacrylamide) (PNiPAM) microgel building blocks are shown to undergo an assemble–freeze–disassemble process. The microgel assemblies, which are controlled by monitoring the attractive and repulsive potentials between the soft colloidal particles, are then frozen by forming inter‐particle metal–terpyridine bis‐complexes upon addition of the metallic cation (such as Fe^II, Co^II). By oxidation of the metal–terpyridine bis‐complex links, the aggregates open up, which is due to the complex dissociation releasing the connected particles in the form of single microgels. We extended our work to the development of 1D filaments and 2D membranes materials made of soft particles connected via supramolecular chemistry.     

典型锕系超分子组装体的构筑原理及研究进展

锕系超分子化学是锕系元素化学的重要研究领域,可以为乏燃料后处理的配位化学基础研究提供重要信息,并为探索锕系功能材料在发光、传感、催化和分离等方面的功能应用提供关键材料体系。本文介绍了基于锕系金属离子的金属-有机超分子组装体这一新兴领域的最新研究进展。从锕系超分子组装体的构筑原理出发并结合笔者自身研究情况,对基于主客体准轮烷配体的锕系-轮烷配位聚合物、具有闭合结构的锕系配位组装体和基于超分子相互作用的锕系超分子聚合物这三类典型的锕系超分子组装体的研究进展进行了梳理和总结阐述。期望为未来新型锕系超分子组装体的设计合成提供参考,促进相关领域的进步和发展。     

Applications of Pillar[n]arene‐Based Supramolecular Assemblies

Macrocycles are an important player in supramolecular chemistry. In 2008, a new class of macrocycles, “pillar[n]arenes”, were first discovered. Research efforts in the area of pillar[n]arenes have elucidated key properties, such as their shape, reaction mechanism, host–guest properties, and their versatile functionality, which has contributed to the development of pillar[n]arene chemistry and their applications to various fields. This Minireview describes how pillar[n]arene‐based supramolecular assemblies can be applied to supramolecular gel formation, reactions, light‐harvesting systems, drug‐delivery systems, biochemical applications, separation and storage materials, and surface chemistry.     

Peptide‐Decorated Dendrimers and Their Bioapplications

Peptide‐decorated dendrimers (PDDs) are a class of spherical, regular, branched polymers that are modified by peptides covalently attached to their surface. PDDs have been used as protein mimetics, novel biomaterials, and in a wide range of biomedical applications. Since their design and development in the late eighties, poly‐l ‐lysine has been a preferred core structure for PDDs. However, numerous recent innovations in polymer synthesis and ligation chemistry have re‐energized the field and led to the emergence of well‐defined peptide dendrimers with more diverse core structures and functions. This Minireview highlights the development of PDDs driven by significantly improved ligation chemistry incorporating structurally well‐defined peptides and the emerging use of PDDs in imaging and drug development.     

Strategies for the construction of supramolecular assemblies from poly-NHC ligand precursors

The field of supramolecular assemblies has developed rapidly in the last few decades, thanks in a large part to their diverse applications. These assemblies have been mostly based on Werner-type coordination motifs in which metal centres are coordinated by nitrogen or oxygen donors. Recently, N-heterocyclic carbene(NHC) ligands have been employed as carbon donors not only because of their appealing structures but also due to the extensive applications in catalysis, biomedicine and material science of the resulting assemblies. During the last decade, NHC-based supramolecular assemblies have witnessed rapid growth and extensive application in molecular recognition, luminescent materials and catalysis. For different topological systems, a diverse selection of poly-NHC precursors and synthetic strategies is crucial to precisely control the synthesis of supramolecular architectures. Several synthetic strategies have been developed to synthesise two-dimensional(2D) molecular metallacycles and three-dimensional(3D) metallacages from a wide range of poly-NHC precursors, including a straightforward one-pot strategy,supramolecular transmetalation, stepwise synthesis, an improved one-pot strategy involving self-sorting behaviour of 3D metallacages and a subtle variation strategy of poly-NHC ligand precursors. This review offers a summary of the synthetic strategies applied for the construction of different poly-NHC-based supramolecular assemblies, particularly emphasizes recent progress in the synthesis of large and complex supramolecular assemblies from poly-NHC precursors, and further attention is given to their application in postsynthetic modifications(PSMs), host-guest chemistry, luminescent properties and biomedical applications.     

Supramolecular Photothermal Effects: A Promising Mechanism for Efficient Thermal Conversion

Supramolecular assemblies have been very successful in regulating the photothermal conversion efficiency of organic photothermal materials in a simple and flexible way, compared with conventional molecular synthesis. In these assemblies, it is the inherent physiochemical mechanism that determines the photothermal conversion, rather than the assembly strategy. This Minireview summarizes supramolecular photothermal effects, which refer to the unique features of supramolecular chemistry for regulating the photothermal conversion efficiency. Emphasis is placed on the mechanisms of how self‐assembly affects the photothermal performance. The supramolecular photothermal effects on various types of light‐harvesting species are discussed in detail. The timely interpretation of supramolecular photothermal effects is promising for the future design of the photothermal materials with high efficiency, precision, and multiple functionalities for a wide array of applications.     

An Antiaromatic Electrode‐Active Material Enabling High Capacity and Stable Performance of Rechargeable Batteries

Although aromatic compounds occupy a central position in organic chemistry, antiaromatic compounds have demonstrated little practical utility. Herein we report the application of an antiaromatic compound as an electrode‐active material in rechargeable batteries. The performance of dimesityl‐substituted norcorrole nickel(II) complex (NiNC) as a cathode‐active material was examined with a Li metal anode. A maximum discharge capacity of about 207 mAhg^?1 was maintained after 100 charge/discharge cycles. Moreover, the bipolar redox property of NiNC enables the construction of a Li metal free rechargeable battery. The high performance of NiNC batteries demonstrates a prospective feature of stable antiaromatic compounds as electrode‐active materials.     

Single‐Molecule Observation of Intermediates in Bioorthogonal 2‐Cyanobenzothiazole Chemistry

We report a single‐molecule mechanistic investigation into 2‐cyanobenzothiazole (CBT) chemistry within a protein nanoreactor. When simple thiols reacted reversibly with CBT, the thioimidate monoadduct was approximately 80‐fold longer‐lived than the tetrahedral bisadduct, with important implications for the design of molecular walkers. Irreversible condensation between CBT derivatives and N‐terminal cysteine residues has been established as a biocompatible reaction for site‐selective biomolecular labeling and imaging. During the reaction between CBT and aminothiols, we resolved two transient intermediates, the thioimidate and the cyclic precursor of the thiazoline product, and determined the rate constants associated with the stepwise condensation, thereby providing critical information for a variety of applications, including the covalent inhibition of protein targets and dynamic combinatorial chemistry.     

Oligo(ethylene glycol)/alkyl‐modified Chromophore Assemblies for Photon Upconversion in Water

Molecular self‐assembly is a powerful means to construct nanoscale materials with advanced photophysical properties. Although the protection of the photo‐excited states from oxygen quenching is a critical issue, it still has been in an early phase of development. In this work, we demonstrate that a simple and typical molecular design for aqueous supramolecular assembly, modification of the chromophoric unit with hydrophilic oligo(ethylene glycol) chains and hydrophobic alkyl chains, is effective to avoid oxygen quenching of triplet–triplet annihilation‐based photon upconversion (TTA‐UC). While a TTA‐UC emission is completely quenched when the donor and acceptor are molecularly dispersed in chloroform, their aqueous co‐assemblies exhibit a clear upconverted emission in air‐saturated water even under extremely low chromophore concentrations down to 40 μm . The generalization of this nano‐encapsulation approach offers new functions and applications using oxygen‐sensitive species for supramolecular chemistry.     

Visible‐Light‐Excited Room‐Temperature Phosphorescence in Water by Cucurbit[8]uril‐Mediated Supramolecular Assembly

Solid‐state materials with efficient room‐temperature phosphorescence (RTP) emissions have found widespread applications in materials science, while liquid or solution‐phase pure organic RTP emission systems has been rarely reported, because of the nonradiative decay and quenchers from the liquid medium. Reported here is the first example of visible‐light‐excited pure organic RTP in aqueous solution by using a supramolecular host‐guest assembly strategy. The unique cucurbit[8]uril‐mediated quaternary stacking structure allows tunable photoluminescence and visible‐light excitation, enabling the fabrication of multicolor hydrogels and cell imaging. The present assembly‐induced emission approach, as a proof of concept, contributes to the construction of novel metal‐free RTP systems with tunable photoluminescence in aqueous solution, providing broad opportunities for further applications in biological imaging, detection, optical sensors, and so forth.     

Luminescent Metallo‐Supramolecular Polymers

Luminescent metallo‐supramolecular polymers are a type of functional supramolecular architectures which integrates the advantages of emission, metal‐coordination, supramolecular chemistry as well as polymeric properties to realize advanced functions. Due to the abundant stimuli‐responsiveness of supramolecular assemblies and the light‐emitting properties, they have been widely applied as chemo‐sensors, light‐emitting devices, contrast agents for bio‐imaging, etc. In this review, we classify luminescent metallo‐supramolecular polymers based on the types of species (lanthanides, organometallic compounds, oligomer or polymer‐based ligands, small‐molecule‐based organic ligands) used to generate the luminescence and summarize recent developments of luminescent metallo‐supramolecular polymers. We mainly focus on the functions and applications of luminescent metallo‐supramolecular polymers and hope to give our reader a snapshot of research on luminescent metallo‐supramolecular polymers and encourage more scientists to devote into this promising area.     

Responsive Linear‐Dendritic Block Copolymers

The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self‐assembly properties. There are three main strategies for the synthesis of linear‐dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self‐assembly properties of interest in different technological areas. The incorporation of stimuli‐responsive moieties gives rise to smart materials that are generally processed as self‐assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light‐responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented.

     

Self‐assembly: An intriguing relationship between structures of metal complexes and shapes of ancient Chinese characters

Self‐assembly is a fundamental principle, which generates structural organization on all scales from molecules to galaxies. In the field of chemistry and materials science, the self‐assembly process driven by noncovalent interactions offers considerable advantages over the stepwise bond formation in the construction of large supramolecular assemblies with different sizes and shapes. The structures of metal clusters are mainly constructed from the assembly of mononuclear metal center to dinuclear, trinuclear species, and so on. It is of interest that Chinese ancient people also used this concept to create and encrypt characters. Herein, we report on an intriguing relationship between structures of metal complexes and the shapes of ancient Chinese characters, in which the self‐assembly principle is clearly demonstrated.     

Aqueous Anion Receptors through Reduction of Subcomponent Self‐Assembled Structures

To prepare new functional covalent architectures that are difficult to synthesize using conventional organic methods, we developed a strategy that employs metal–organic assemblies as precursors, which are then reduced and demetalated. The host–guest chemistry of the larger receptor thus prepared was studied using NMR spectroscopy and fluorescence experiments. This host was observed to strongly bind aromatic polyanions in water, including the fluorescent dye molecule pyranine with nanomolar affinity, thus allowing for the design of an indicator‐displacement assay.     

Routes to Hydrogen Bonding Chain‐End Functionalized Polymers

The contribution of supramolecular chemistry to polymer science opens new perspectives for the design of polymer materials exhibiting valuable properties and easier processability due to the dynamic nature of non‐covalent interactions. Hydrogen bonding polymers can be used as supramolecular units for yielding larger assemblies that possess attractive features, arising from the combination of polymer properties and the responsiveness of hydrogen bonds. The post‐polymerization modification of reactive end‐groups is the most common procedure for generating such polymers. Examples of polymerizations mediated by hydrogen bonding‐functionalized precursors have also recently been reported. This contribution reviews the current synthetic routes toward hydrogen bonding sticker chain‐end functionalized polymers.