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Acceptor engineered supramolecular photosensitizers with a proming phototoxicity index (PI) for effective and safe photodynamic therapy in vivo.

Ruthenium (Ru) complexes are developed as latent emissive photosensitizers for cancer and pathogen photodiagnosis and therapy. Nevertheless, most existing Ru complexes are limited as photosensitizers in terms of short excitation and emission wavelengths. Herein, we present an emissive Ru(II) metallacycle (herein referred to as 1) that is excited by 808-nm laser and emits at a wavelength of ∼1,000 nm via coordination-driven self-assembly. Metallacycle 1 exhibits good optical penetration (∼7 mm) and satisfactory reactive oxygen species production properties. Furthermore, 1 shows broad-spectrum antibacterial activity (including against drug-resistant Escherichia coli ) as well as low cytotoxicity to normal mammalian cells. In vivo studies reveal that 1 is employed in precise, second near-infrared biomedical window fluorescent imaging–guided, photo-triggered treatments in Staphylococcus aureus –infected mice models, with negligible side effects. This work thus broads the applications of supramolecular photosensitizers through the strategy of lengthening their wavelengths.

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)–platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen ( 1 O 2 ) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 μM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.

An inclusion complex of a trigonal-prismatic metallacage with two coronene guests was constructed by multicomponent coordination-driven self-assembly from a 90° platinum(II) acceptor [

Materials with aggregation-induced emission (AIE) properties are of growing interest due to their widespread applications. AIEgens, such as tetraphenylethylene units, display varying emission behaviors during their conformational changes. However, the structure-property relationships of the intermediate conformations have rarely been explored. Herein, we show that the conformational restriction on TPE units can affect the structural relaxation in the excited state and the resulting photophysical behaviors. Specifically, three metallacages of different sizes were prepared via the coordination-driven self-assembly of a TPE-based tetrapyridyl donor with length-increasing Pt(II) acceptors. While the metallacages share similar scaffolds, they exhibit a trend of red-shifted fluorescence and attenuated quantum yield with the increase of their sizes. Furthermore, spectroscopic and computational studies together with a control experiment were conducted, revealing that the degree of cage tension imposed on the excited-state conformational relaxation of TPE moieties resulted in their distinct photophysical properties. The precise control of conformation holds promise as a strategy for understanding the AIE mechanism as well as optimizing the photophysical behaviors of materials on the platform of supramolecular coordination complexes.

Supramolecular coordination complexes formed by coordination-induced assembly not only avoid the loss of activity of precursors but also provide an efficient way for controlled release, which can be further used in various fields of biology such as drug delivery, cell imaging, and tumor treatment. In this work, a Pt

Two trigonal prismatic metallacages 1 and 2 bearing triphenylamine and anthracene moieties are designed and synthesized to fabricate artificial light-harvesting systems (LHSs). These two cages are prepared via the coordination-driven self-assembly of two anthracene-triphenylamine-based tripyridyl ligand 3, three dicarboxylates, and six 90° Pt(II) acceptors. The design of the anthracene-triphenylamine chromophore makes possible the tunable excited-state property (like the emissive transition energy and lifetime) as a function of the solvent polarity, temperature, and concentration. The synergistic photophysical footprint of these metallacages, defined by their high absorptivity and emission quantum yield (QY) relative to the free ligand 3, signifies them as a superior light sensitizer component in an LHS. In the presence of the fluorescent dye Nile Red (NR) as an energy acceptor, the metallacages display efficient (>93%) excited energy transfer to NR through an apparent static quenching mechanism in viscous dimethyl sulfoxide solvent.

Two quadrilateral metallacycles were prepared by coordination-driven self-assembly of a 90° platinum(II) receptor 6 with a flexible donor 1,3-bis(4,4′-bipyridinium)propane 1a or 1,1-bis(4,4′-bipyridinium)methane 1b, respectively. Three [3]catenanes (3, 4 and 5) were further prepared by in situ addition of crown ethers (DB24C8 or DB30C10) to the yielded metallacycles. By comparing the crystal structures of 1a and 4, it was found that the bite angle change of the flexible bidentate donor 1a (111.0° to 112.3°) is much smaller than that of rigid platinum(II) receptor 6 (90.0° to 83.2°) during metalla-cyclization. The multicomponent [3]catenanes were stabilized by multiple supramolecular interactions, including metal coordination, π–π stacking, charge transfer, and hydrogen bonding.

The accurate control of multicomponent self-assembly to fabricate a single assembly is still a challenge. Herein we describe multicomponent coordination-driven self-assembly with appropriately desi...

Chiral metal-organic complexes hold great promise as new functional materials that exhibit unique stereochemical and optical properties. Here, we report the formation of optically pure pillar[5]arene-based platinum chiral metallacycles. By coordination with 60° and 90° Pt(II) acceptors, planar chiral platinum triangles were self-assembled efficiently and characterized by multiple spectroscopic techniques. Optical studies indicated that these metallacycles had chiral properties: pS enantiomers showed a negative Cotton effect, and pR enantiomers exhibited a positive Cotton effect. In addition, these metallacycles also exhibited circularly polarized luminescence.

Poor processability of fullerenes is a major remaining drawback for them to be studied monomolecularly and to find real-life applications. One of the strategies to tackle this problem is to encapsu...

The utilization of structural water in chemical self-assembly has not only effectively eliminated the negative influences of solvents from solutions or gels but has also provided new insight into the fabrication of new materials in bulk. However, up to now, supramolecular polymerization triggered by structural water has been dominated more by serendipity than rational design. After carefully analyzing the chemical structures of artificial monomers and gaining a deep understanding of the water-triggered assembly process, we report herein the bulk formation of polymeric materials from water and low-molecular weight monomers by rational design instead of serendipity.

Hierarchical self-assembly of discrete organoplatinum(II) metallacycles has attracted considerable attention. However, the exact assembly mechanism involving non-covalent interactions has limited the formation and application of self-assembly due to the dynamics of platinum metallacycles. Herein, we report the hierarchical self-assembly of a pyrene-based discrete organoplatinum(II) double-metallacycle that takes advantage of heteroligation-coordination-driven self-assembly and triflate anions' hydrogen bonding, which is extended into a 3-D supramolecular framework by the hydrogen-bonding interactions involving triflate anions. Furthermore, the assembled system displays tunable fluorescence emission and enhanced solid emission. The studies herein disclosed pave the way to prepare platinum(II) metallacycle-based supramolecular functional materials.

Stimuli-responsive complexes have attracted significant interest in supramolecular chemistry and material science. In this study, a new organoplatinum-crown supramolecular complex has been successfully constructed via the coordination of benzo-21-crown-7 (B21C7) units and cis-Pt(PEt3)2(OTf)2. The resulting complex displays intriguing lower critical solution temperature (LCST) and anion-sensitive deassembly behavior. This organoplatinum-crown ether complex with dual-responsive behavior is a promising candidate for stimuli-responsive materials.

Introducing self-assembly strategies into the construction of catalysts has been proven to have great advantages in asymmetric catalysis. We constructed two chiral metalla-triangles by highly efficient coordination-driven self-assembly from a chiral 3,3'-dipyridyl-substituted BINOL donor. They were successfully applied in asymmetric conjugate addition of a series of α,β-unsaturated ketones with trans-styrylboronic acids. The use of these metalla-triangles as supramolecular catalysts is obviously conducive to the enhancement of catalytic activity and stereoselectivity in the presented addition reactions. Under induction of the chiral metalla-triangles, an array of α,β-enones were converted to chiral γ,δ-unsaturated ketones in medium to quantitative yields (40-98%) with high enantioselectivities (87-96% ee).

Post-assembly modification is a useful tool for producing discrete metallasupramolecular structures. However, the simple structural transformation by facile covalent reactions greatly impedes the d...

Supramolecular copolymers with complex architectures and emergent functions constitute a class of challenging but enticing synthetic targets in polymer science. Individual building blocks can be tailored to endow a resulting supramolecular copolymer with increased structural and functional complexity. Herein, we describe the construction of a linear supramolecular copolymer comprising mechanically interlocked segments with hydrogen-bonding metallorhomboidal units. Specifically, a hierarchical supramolecular polymerization of a crown ether-based [2]rotaxane and a discrete organoplatinum(II) metallacycle driven by 2-ureido-4-pyrimidinone (UPy) quadruple hydrogen bonding provides the impetus for its formation. This system demonstrates enhanced structural complexity accessed by the unification of orthogonal noncovalent interactions: metal coordination, host–guest chemistry, and multiple hydrogen bonding interfaces.

A platinum(II) metallacycle-cored supramolecular network based on a metal-salen complex was successfully constructed by two orthogonal noncovalent interactions (host-guest interactions and metal coordination interactions). The obtained metallo-supramolecular polymer could further form gels when the concentration of metallacycle

Enzyme-responsive nanomaterials are emerging as important candidates for bioanalytical and biomedical applications due to their good biocompatibilities and sensitivities. However, the lack of promising operation platforms compatible with enzyme responsiveness greatly limits the scope and functionality of smart materials. Herein, we report the design and synthesis of a naphthalene-functionalized organoplatinum(II) metallacycle

Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acid–functionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.

It is well known that chemical compositions and structural arrangements of materials have a great influence on their resultant properties. Diverse functional materials have been constructed by using either biomolecules (peptides, DNA, and RNA) in nature or artificially synthesized molecules (polymers and pillararenes). The relationships between traditional building blocks (such as peptides) have been widely investigated, for example how hydrogen bonds work in the peptide multistage assembly process. However, in contrast to traditional covalent bond-based building blocks-based assembly, suprastructures formed by noncovalent bonds are more influenced by specific bond features, but to date only a few results have been reported based on noncovalent bond-based building block multistage assembly. Here, three metal–organic cycles (MOCs) were used to show how coordination bonds influence the bimetallacycle conformation then lead to the topology differences of MOC multilevel ordered materials. It was found that the coordination linker (isophthalate-Pt-pyridine) is an important factor to tune the shape and size of the MOC-derived suprastructures.

Developing artificial light-harvesting scaffolds with a cascade energy transfer process is significant for better understanding of photosynthesis. Here, we report [3+3] self-assembled Pt

Control over the stimuli-responsive behavior of smart molecular systems can influence their capability to execute complex functionalities. Herein, we report the development of a suite of spiropyran-based multi-stimuli-responsive self-assembled platinum(II) macrocycles (5-7), rendering coordination-assisted enhanced photochromism relative to the corresponding ligands. 5 showed shrinking and swelling during photoreversal, while 6 and 7 are fast and fatigue-free supramolecular photoswitches. 6 turns out to be a better fatigue-resistant photoswitch and can retain an intact photoswitching ability of up to 20 reversible cycles. The switching behavior of the macrocycles can also be precisely controlled by tuning the pH of the medium. Our present strategy for the construction of rapid stimuli-responsive supramolecular architectures via coordination-driven self-assembly represents an efficient route for the development of smart molecular switches.

Singlet oxygen (1O2), as an important active reagent, has found wide applications in photodynamic therapy (PDT), synthetic chemistry, and materials science. Organic conjugated aromatics serving as hosts to capture and release singlet oxygen have been systematically investigated over the last decades. Herein, we present a [6 + 6] organoplatinum(II) metallacycle by using ∼180° dipyridylanthracene donor and ∼120° Pt(II) acceptor as the building blocks, which enables the capture and release of singlet oxygen with relatively high photooxygenation and thermolysis rate constants. The photooxygenation of the metallacycle to the corresponding endoperoxide was performed by sensitized irradiation, and the resulting endoperoxide is stable at room temperature and can be stored under ambient condition over months. Upon simple heating of the neat endoperoxide under inert atmosphere at 120 °C for 4 h, the resulting endoperoxide can be reconverted to the corresponding parent form and singlet oxygen. The photooxygenation and thermolysis products were characterized by NMR spectroscopy and electrospray ionization time-of-flight mass spectrometric analysis. Density functional theory calculations were conducted in order to reveal the frontier molecular orbital interactions and reactivity. This work provides a new material platform for singlet oxygen related promising applications.

Coordination-driven suprastructures have attracted much interest due to their unique properties. Among these structures, platinum-based architectures have been broadly studied due to their facile preparation. The resultant two- or three-dimensional (2D or 3D) systems have many advantages over their precursors, such as improved emission tuning, sensitivity as sensors, and capture and release of guests, and they have been applied in biomedical diagnosis as well as in catalysis. Herein, we review the recent related to platinum-based coordination-driven self-assembly (CDSA), and the text is organized to emphasizes both the synthesis of new metallacycles and metallacages and their various applications. We review the recent developments in the growing field of platinum-based, coordination-driven self-assembly, and bringing together the key results.

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

The dianthracene-based rhomboidal organoplatinum(II) metallacycle 1 was successfully obtained via coordination-driven self-assembly involving the combination of diplatinum(II) acceptor 2 and dipyri...

In this work, we present the formation of two open-ended hexagonal-prism tubular macrocycles by the [6+12] self-assembly of the symmetric ~120° organic ligand donor with ~90° Pt(II) acceptor in a 1:2 ratio. The assembled structures were characterized by multinuclear NMR ((1)H NMR, (31)P{(1)H} NMR, and (1)H−(1)H COSY NMR), electrospray ionization mass spectrometry (ESI-TOF-MS), traveling wave ion mobility-mass spectrometry (TWIM-MS), and transmission electron microscopy. Molecular modeling was further conducted to get insight into their structured characteristics. We also examined their photophysical properties.

International audience; Light-harvesting is one of the key steps in photosynthesis, but developing artificial light-harvesting systems (LHSs) with high energy transfer efficiencies has been a challenging task. Here we report fluorescent hexagonal Pt(II) metallacycles as a new platform to fabricate artificial LHSs. The metallacycles (4 and 5) are easily accessible by coordination-driven self-assembly of a triphenylamine-based ditopic ligand 1 with di-platinum acceptors 2 and 3, respectively. They possess good fluorescence properties both in solution and in the solid state. Notably, the metallacycles show aggregation-induced emission enhancement (AIEE) characteristics in a DMSO-H2O solvent system. In the presence of the fluorescent dye Eosin Y (ESY), the emission intensities of the metallacycles decrease but the emission intensity of ESY increases. The absorption spectrum of ESY and the emission spectra of the metallacycles show a considerable overlap, suggesting the possibility of energy transfer from the metallacycles to ESY, with an energy transfer efficiency as high as 65% in the 4a+ESY system. © 2019 American Chemical Society.

Diverse metal-organic complexes (MOCs), shaped as rectangles, triangles, hexagons, prisms, and cages, can be formed by coordination between metal ions (Pt, Pd, Ru, Rh, Ir, Zn, Co, and Cd) and organic ligands, with potential applications as alternatives to conventional biomedical materials for therapeutic, sensing, and imaging purposes. MOCs have been investigated as anticancer drugs in the treatment of malignant tumors in lung, cervical, breast, colon, liver, prostate, ovarian, brain, stomach, bone, skin, mouth, thyroid, and other cancers. MOCs with one, two, and three cavities have also been investigated as drug carriers and prepared for the loading and release of different drugs. In addition, MOCs can target proteins by the shape effect and recognize sugars and DNA by electrostatic interactions, as well as estradiol by host-guest interactions, etc. This Perspective mainly covers achievements in the biomedical application of MOCs. We aim to identify some key trends in the reported MOC structures in relation to their biomedical activity and potential applications.

Discrete Pt(II) metallacycles have potential applications in biomedicine. Herein, we engineered a dual-modal imaging and chemo-photothermal therapeutic nano-agent 1 that incorporates discrete Pt(II) metallacycle 2 and fluorescent dye 3 (emission wavelength in the second near-infrared channel [NIR-II]) into multifunctional melanin dots with photoacoustic signal and photothermal features. Nano-agent 1 has a good solubility, biocompatibility, and stability in vivo. Both photoacoustic imaging and NIR-II imaging in vivo confirmed that 1 can effectively accumulate at tumor sites with good signal-to-background ratio and favorable distribution. Guided by precise dual-modal imaging, nano-agent 1 exhibits a superior antitumor performance and less severe side effects compared with a single treatment because of the high efficiency of the chemo-photothermal synergistic therapy. This study shows that nano-agent 1 provides a promising multifunctional theranostic platform for potential applications in biomedicine.

Coordination-driven self-assembly (CDSA) is increasingly used to synthesize coordination complexes containing metal-centered electron acceptors and typically nitrogen-containing electron donors. Characterization of the structures obtained from CDSA via crystallographic or spectroscopic means is limited due to difficulties in forming single crystals for X-ray studies and overlapping precursor and product signals in NMR. Here, we employ ion mobility-mass spectrometry (IM-MS), which provides a direct measure of size and shape of the CDSA complexes, to study the intact reaction products of a rhomboid-shaped complex. This approach negates the need for product isolation and crystallization and allows for tracking of the product distribution as a function of time. A potential challenge of IM-MS is that the size/shape of the observed CDSA complexes can vary with internal energy; however, we show that proper tuning of the instrument reduces the effects of collisional activation thereby allowing for retention of ion conformations that reflect solution-phase ion structures. Graphical Abstract.

A double metallacycle was prepared via the size-selective integrative self-sorting of four different building blocks driven by a reversible metal-ligand coordination interaction. A hydrophobic dendron was placed on a metallacycle and a hydrophilic dendron was attached to the other metallacycle, producing a two-faced Janus-type supramolecule with two distinct functionalities. In aqueous media, hierarchical self-assembly of the supramolecular system was induced by the combination of coordination interactions and hydrophobic-hydrophilic interactions resulting in the formation of micrometer-sized fiber-like structures, a morphology distinct from metallacycles bearing only one type of functionality. This study provides a versatile approach for the construction of Janus-type molecules and demonstrates that integrative self-sorting of a supramolecular coordination system can be utilized for the preparation of complex supramolecular systems with pre-designed functionalities and morphologies