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Investigating the self‐sorting behaviour of assemblies with subtle structural differences is a captivating yet challenging endeavour. Herein, we elucidate the unusual self‐sorting behaviour of metallacages with subtle structural differences in batch reactors and microdroplets. Narcissistic self‐sorting of metallacages has been observed for two ligands with identical sizes, shapes, and symmetries, with only minor differences in the substituted groups. In particular, the self‐sorting process in microdroplets occurs within 1 min at room temperature, in stark contrast to batch reactors, which require equilibration for 30 min. To reveal the mechanism of self‐sorting and the role of microdroplets, we conducted a series of experiments and theoretical calculations, including competitive self‐assembly, cage‐to‐cage transformation, control experiments involving model metallacages with larger cavities, noncovalent interaction analysis, and root mean square deviation (RMSD) analysis. This research demonstrates an unusual case of self‐sorting of very similar assemblies and provides a new strategy for facilitating the self‐sorting efficiency of supramolecular systems. [ABSTRACT FROM AUTHOR]

Chiral metallacages, with their precisely distributed luminescent and chiral units and inherent adaptive chirality, represent an ideal framework for developing circularly polarized luminescence (CPL)‐active materials. Despite their potential, enhancing the luminescence dissymmetry factor (glum) of metallacage‐based materials remains a significant challenge. In this study, a useful approach is proposed by co‐assembling the chiral donor metallacage Δ4/Λ4‐Zn4A4 with the achiral acceptor Nile red (NiR), achieving efficient energy and chirality transfer and resulting in enhanced CPL in these co‐assemblies. More importantly, microfluidic laminar flow is utilized, known for providing stable driving forces and confined spaces, to achieve a marked improvement in the glum values of these co‐assemblies within polymethyl methacrylate (PMMA) films. Computational fluid dynamics (CFD) simulations and small‐angle X‐ray scattering (SAXS) experiments confirm that films containing Δ4/Λ4‐Zn4A4/NiR, prepared via microfluidic chips, display well‐defined distributions of metallacages and NiR due to the controllable assembly process facilitated by microfluidic laminar flow. This work pioneers a new methodology to significantly enhance the glum of metallacage‐based CPL materials, opening new avenues in the field of chiral photonics. [ABSTRACT FROM AUTHOR]

Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self‐assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage‐based ion channels have well‐defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide‐based artificial chloride ion channel is constructed through efficient subcomponent self‐assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion‐current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations. [ABSTRACT FROM AUTHOR]

Abstract Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self‐assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage‐based ion channels have well‐defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide‐based artificial chloride ion channel is constructed through efficient subcomponent self‐assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion‐current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations.

Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation. [ABSTRACT FROM AUTHOR]

Integration of small organic fluorophores into supramolecular systems through coordination-driven self-assembly is gaining increasing interest in the areas of fluorescent materials, chemical sensors, and biomedical applications. Compared to systems modified with a single type of fluorophore, the introduction of two or more kinds of fluorophores can achieve multi-channel spectral changes in absorption and emission, enabling ratiometric detection and tunable light emission. Metal coordination not only allows precise control over the number and location of small organic fluorophores in supramolecular systems, but also enables integrating of small molecular fluorophores with specified light-absorbing and light-emitting properties, including single- or multi-step FRET, multi-channel ratio imaging, broader light-absorbing bands, and higher catalytic efficiency. This review focuses on constructing supramolecular assemblies through coordination-driven self-assembly with ligands modified by small organic fluorophores as core skeleton, and summaries recent progress in developing and applying these assemblies for artificial light-harvesting systems, biological applications, assembly kinetics study and cancer theranostics. [ABSTRACT FROM AUTHOR]

The structural regulation and functional development of supramolecular macrocycle and cage remains an interesting topics in the scientific community. Here, two bidentate and tetradentate tetraphenylethylene-based pyridine ligands were designed rationally. Utilizing the size variation of different organometallic rhodium building blocks, and coordination driven self-assembly strategy, three dinuclear metallatriangles and three octanuclear metallacages were synthesized. These structures have been fully demonstrated through single crystal X-ray diffraction technology, NMR spectrum and ESI-TOF-MS. Besides, strong near-infrared absorption prompts us to explore their near-infrared photothermal conversion effect. The results demonstrated that there is a clear correlation between the ability of photothermal conversion and the structural characteristics of building units. This study provides a good research approach for designing and synthesizing new photothermal conversion materials featuring excellent performance. Three dinuclear metallatriangles and three octanuclear metallacages were synthesized by utilizing two tetraphenylethylene-based pyridine ligands based on the size variation of organometallic rhodium building blocks. These structures were fully demonstrated through single crystal X-ray diffraction technology, NMR spectrum and ESI-TOF-MS. In addition, significantly different near-infrared photothermal conversion was observed. [Display omitted] • Three dinuclear metallatriangles and three octanuclear metallacages were synthesized by utilizing size variation of organometallic rhodium building blocks and coordination driven self-assembly strategy. • These structures have been demonstrated through single crystal X-ray diffraction technology, NMR spectrum and ESI-TOF-MS. And the existence of tension prevents the formation of molecular double rings. • Strong near-infrared photothermal conversion effect were observed for these complexes, which was correlated with the structural characteristics of building units. [ABSTRACT FROM AUTHOR]

Despite recent efforts to advance host‐guest systems using discrete metal‐organic cages (MOCs) with non‐trivial topological geometries for molecular recognition, which is often mediated by non‐covalent interactions involving aromatic functional groups, the relative complexation of these so‐called π‐π interaction is still challenges of study, theory and modeling. Specifically, the ability of supramolecular interactions, for an example, π‐π stacking between guest substrates and MOCs as hosts, would easily control the host‐guest assemblies. By the assembly of host‐guest complexations with metal‐coordination driven strategy and π‐π interaction, here we show that the hierarchical combination of the newly metal‐organic cages with nanosized cavity (metallacage 1), which facilitates encapsulating guest molecules through supramolecular forces. Additionally, the electron‐donating (ED)/‐withdrawing (EW) functional groups of pyrene analogues, utilized as guest substrates, can enforce host‐guest assemblies with electron‐donor (D) and electron‐acceptor (A) interactions. We herein demonstrate that ED or EW group can promote host‐guest behaviors. By this new approach, we predict that the more stable host‐guest complexations will be accompanied by stronger D−A interactions. Three guest substrates, including 1‐hydroxypyrene, 1‐pyrenamine, and 1‐pyrenecarboxaldehyde, were chosen to systematically study this host‐guest system within 1, exhibiting well consistent with our hypothesis. [ABSTRACT FROM AUTHOR]

Platinum containing metallacages and metallacage-based nanospheres were prepared by interface assembly. The suprastructure type can be adjusted by modifying substituents in the metallacage. At the same concentration, metallacage-based microrods were prepared when the amino group was replaced by hydrogen in the pillar. [ABSTRACT FROM AUTHOR]

Charge-transfer (CT) interactions between co-facially aligned π-donor/acceptor (π-D/A) arrays engender unique optical and electronic properties that could benefit (supra)molecular electronics and energy technologies. Herein, we demonstrate that a tetragonal prismatic metal-organic cage (MOC1 8+ ) having two parallel π-donor tetrakis(4-carboxyphenyl)-Zn-porphyrin (ZnTCPP) faces selectively intercalate planar π-acceptor guests, such as hexaazatriphenylene hexacarbonitrile (HATHCN), hexacyanotriphenylene (HCTP), and napthanelediimide (NDI) derivatives, forming 1:1 πA@MOC1 8+ inclusion complexes featuring supramolecular π-D/A/D triads. The π-acidity of intercalated π-acceptors (HATHCN ≫ HCTP ≈ NDIs) dictated the nature and strength of their interactions with the ZnTCPP faces, which in turn influenced the binding affinities ( K a ) and optical and electronic properties of corresponding πA@MOC1 8+ inclusion complexes. Owing to its strongest CT interaction with ZnTCPP faces, the most π-acidic HATHCN guest enjoyed the largest K a (5 × 10 6 M -1 ), competitively displaced weaker π-acceptors from the MOC1 8+ cavity, and generated the highest electrical conductivity (2.1 × 10 -6 S/m) among the πA@MOC1 8+ inclusion complexes. This work demonstrates a unique through-space charge transport capability of πA@MOC1 8+ inclusion complexes featuring supramolecular π-D/A/D triads, which generated tunable electrical conductivity, which is a rare but much coveted electronic property of such supramolecular assemblies that could further expand their utility in future technologies.

The design and development of metallosupramolecular systems has resulted in construction of a myriad of fascinating structures with highly diverse properties and potential applications. Assessment of the biomedical applications of metallosupramolecular assemblies is an emerging field of research that stems from the recently demonstrated promising results on such systems. After the pioneering works of Therrien and coworkers on organometallic Ru-cages with promising anticancer properties, this topic has evolved to the more recent studies on bioactivity of supramolecular coordination complexes built from different metal ions and various multidentate ligands. Sufficient amount of data on the anticancer activity of metallosupramolecules has already been reported and allows outlining some general tendencies in the structural aspects of the biological activity. The main structural properties of the complexes that can be readily modified to enhance their activity are the size, the shape and charge of the formed complexes. Moreover, the intrinsic properties of the building components could predetermine some of the main characteristics of the overall supramolecular complex, such as its optical properties, chemical reactivity, solubility, etc., and could, thereby, define the areas of its biomedical applications. The unique structural property of most of the metallosupramolecular assemblies, however, is the presence of a discrete cavity that renders a whole range of additional applications resulting from specific host-guest interactions. The encapsulations of small bioactive or fluorescent molecules have been employed for delivery or recognition purposes in many examples. On the other hand, metallosupramolecules have been imbedded into target-specific polymeric nanoparticles that resulted in a successful combination of their therapeutic and diagnostic properties, making them promising for theranostic application in cancer treatment. The aim of this review paper is to mark out some key tendencies in the reported metallosupramolecular structures in relation with their biological activity and potential areas of biomedical application. In this way, a useful set of guidelines can be delineated to help synthetic chemists broaden the application areas of their supramolecular systems by few structural changes.

Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation.

Metallacage-based macroscopic films were prepared by interfacial assembly, which could be further used as a functional unit to assemble the film-containing smart emissive devices. More importantly, the introduction of various luminescent molecules into the hydrogel resulted in various emissive devices that enabled mimicking and optimization of its emission systems. The combination of metallacage-based film and other fluorescent molecules in the polymeric network leads to the tunable luminescence of thermo-responsive hydrogel devices. [Display omitted] • Metallacage-based macroscopic film is prepared by interfacial assembly. • Macroscopic film is used as a functional unit to assemble the smart emissive devices. • Thermo-responsive polymeric hydrogel devices exhibit tunable luminescence. [ABSTRACT FROM AUTHOR]

Two types of metal–organic capsule and cage based on dipalladium(II) corners, have been synthesized by π···π interactions and metal-coordination-driven hierarchical self-assembly approach, which are extended into 2D supramolecular networks by the π···π packing and other weak intermolecular interactions. [Display omitted] • Two types of metal–organic capsule and cage based on dipalladium(II) corners have been synthesized by π···π interactions and metal-coordination-driven hierarchical self-assembly approach. • The 2D supramolecular networks are contructed by the π···π packing and other weak intermolecular interactions. Hierarchical self-assembly of novel supramolecular networks has attracted considerable attention. Herein we report the design and synthesis of pyrene-based metallacapsules and metallacages via π···π interactions and a metal-coordination-driven hierarchical self-assembly approach. These metal–organic structures built from diamide- and triamide-based multi-pyrazolyl ligands and dipalladium(II,II) corners are extended into 2-D supramolecular networks by π···π packing and other weak intermolecular interactions. [ABSTRACT FROM AUTHOR]

A tubular tetranuclear silver(I) N-heterocyclic carbene (NHC) metallacage [Ag 4 (1) 2 (PF 6) 4 was synthesized by in situ deprotonation of a cyclic tetraimidazolium ligand with Ag 2 O. The interaction of obtained octacarbene-based metallacage with aromatic molecules, especially 4,4′-biphenyldicarboxaldehyde in solution was studied by NMR technique. The 4,4′-biphenyldicarboxaldehyde appearing to be located outside of the cavity with multiple C–H⋯O interactions was further confirmed by X-ray crystallography. Additionally, the reaction of the metallacage [Ag 4 (1) 2 (PF 6) 4 with [Cp∗IrCl 2 2 afforded a dinuclear half-sandwich iridium complex [Cp∗ 2 Ir 2 (1)](PF 6) 4 that contains two CNC-pincer-ligated Cp∗Ir fragments. The complex [Cp∗ 2 Ir 2 (1)](PF 6) 4 was characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. A dinuclear complex [Cp∗ 2 Ir 2 (1)](PF 6) 4 that contains two C NHC NC NHC -pincer-ligated Cp∗Ir fragments was obtained from a tubular-like metallacage [Ag 4 (1) 2 (PF 6) 4 via transmetallation method. The interaction of the tubular metallacage [Ag 4 (1) 2 (PF 6) 4 with functional compound, such as 4,4′-biphenyldicarboxaldehyde was also studied. Image 1 • A tubular tetranuclear octacarbene-based metallacage [Ag 4 (1) 2 (PF 6) 4 was synthesized by in situ deprotonation. • The complex [Cp∗ 2 Ir 2 (1)](PF 6) 4 containing two CNC-pincer-ligated Cp∗Ir fragments was obtained by transmetallation strategy. • The interaction of the obtained metallacage with aromatic molecules, especially 4,4′-biphenyldicarboxaldehyde was studied. [ABSTRACT FROM AUTHOR]

Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy., Competing Interests: The authors declare no conflict of interest.

The design and development of metallosupramolecular systems has resulted in construction of a myriad of fascinating structures with highly diverse properties and potential applications. Assessment of the biomedical applications of metallosupramolecular assemblies is an emerging field of research that stems from the recently demonstrated promising results on such systems. After the pioneering works of Therrien and coworkers on organometallic Ru-cages with promising anticancer properties, this topic has evolved to the more recent studies on bioactivity of supramolecular coordination complexes built from different metal ions and various multidentate ligands. Sufficient amount of data on the anticancer activity of metallosupramolecules has already been reported and allows outlining some general tendencies in the structural aspects of the biological activity. The main structural properties of the complexes that can be readily modified to enhance their activity are the size, the shape and charge of the formed complexes. Moreover, the intrinsic properties of the building components could predetermine some of the main characteristics of the overall supramolecular complex, such as its optical properties, chemical reactivity, solubility, etc., and could, thereby, define the areas of its biomedical applications. The unique structural property of most of the metallosupramolecular assemblies, however, is the presence of a discrete cavity that renders a whole range of additional applications resulting from specific host-guest interactions. The encapsulations of small bioactive or fluorescent molecules have been employed for delivery or recognition purposes in many examples. On the other hand, metallosupramolecules have been imbedded into target-specific polymeric nanoparticles that resulted in a successful combination of their therapeutic and diagnostic properties, making them promising for theranostic application in cancer treatment. The aim of this review paper is to mark out some key tendencies in the reported metallosupramolecular structures in relation with their biological activity and potential areas of biomedical application. In this way, a useful set of guidelines can be delineated to help synthetic chemists broaden the application areas of their supramolecular systems by few structural changes.