Coordination-driven self-assembly of metallo-nanodrugs for local inflammation alleviation

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable challenge.In this study,we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug delivery.The resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability,allowing for the combination of magnetic resonance imaging and anti-inflammatory therapy.In the case of osteoarthritis(OA),the metallo-nanodrugs remarkably alleviate synovial inflammation,preventing cartilage destruction and extracellular matrix loss.In addition,it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse model.This work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

Novel 1D Copper（ll） Helical Chain Formed by Weak Coordination-driven Self-assembly： Synthesis, Structure, and Magnetic Property

A novel 1D copper（II） helical chain is constructed through the connection of tetranuclear copper（ll） units [Cu4（L）（Py）4] （H8L=N,N＇-（BINOL-3,3＇-dicarboxyl）-disalicylhydrazide, where BINOL is 1,l＇-binaphthalenyl-2,2＇- diol, py=pyridine） by weak coordination-driven self-assembly, and characterized by IR, single crystal X-ray dif- fraction, thermogravimetric analysis, and X-ray power diffraction analysis. Interestingly, the helical chains are packed in an alternating left-（M） and right-handed （P） chirality, the orientation of the helices was determined by the axial chirality of the ligand. The complex shows antiferromagnetic interactions between the copper centers.

Luminescent terpyridine-based metallo-supramolecular systems:from design to applications

Luminescent metallo-supramolecules have received tremendous attention in recent years owing to their diverse yet well-defined structures,tunable luminescent properties,and broad applications.In this context,the development of terpyridine(tpy)-based luminescent metallo-supramolecular systems has seen rapid growth.This review aims to summarize the recent progress of luminescent metallo-supramolecular assemblies from tpy ligands with metal ions,with a focus on discrete metallo-supramolecular architectures and metallo-supramolecular polymers.The design strategies and common approaches for tuning the luminescence properties are detailed along with representative applications.Finally,the pitfalls and unmet challenges regarding the structural characterization and practical applications of tpy-based metallo-supramolecules are discussed followed by our perspectives on the future directions of this field.

BODIPY-based supramolecular fluorescent metallacages

During the past few years, the construction of BODIPY-based supramolecular fluorescent metallacages through coordination-driven self-assembly has gained increasing interest due to their unique photophysical properties and applications in catalysis, sensing, and bioimaging. In consideration of the rapid development of this field, it is time to summarize recent developments involving BODIPY-based metallacages.In this review, a comprehensive summary of the construction of BODIPY-based metallacages as well as their photophysical properties and applications will be presented.

Topological effect on fluorescence emission of tetraphenylethylene-based metallacages

Herein,we describe the selective formation of a barrel-shaped or a ball-shaped fluorescent metallacage by controlling the shape and stoichiometry of the building blocks.Specifically,the tetraphenylethylene-based donor and two acceptors with different numbers of Pt(Ⅱ)centers were combined via coordination-driven self-assembly.Owing to the differences in the shapes of the assemblies,the resultant ball-shaped metallacage displayed stronger and blue-shifted fluorescence compared to the barrel-shaped one in dilute solutions,while a reversal of fluorescence intensities was observed in the aggregation process.Overall,this work demonstrates that the photophysical properties of supramolecular coordination complexes can be affected by subtle geometrical factors,which can be controlled precisely at the molecular level.

Effects of Metal Cations and Counter Anions on the Structural Stability of Isoquinoline-Based Metallo-Supramolecular Cages

Metallo-supramolecular architectures that are constructed by coordination-driven self-assembly have received tremendous attention on account of their diverse yet molecular-level precise structures and broad applications.Of particular,metal cations and counter anions are fundamentally important in terms of self-assembly,characterization and property;however,their effects on the structural stabilities of metallo-supramolecular architectures have seldom been investigated.To address this issue,herein,a series of octahedral metallo-cages that are capable of tolerating with five metal cations(Pd^(2+),Cu^(2+),Ni^(2+),Co^(2+)and Zn^(2+)),and five counter anions(ClO_(4)^(–),OTf^(–),BF_(4)^(–),NTf_(2)^(–)and NO_(3)^(–))are constructed by the coordination-driven self-assembly of a well-designed tritopic isoquinoline-based ligand with corresponding metal salts.Structural stability studies show that metal cations and counter anions play a critical role in the stability of the resulting cages depending on their coordination abilities and stacking manners.This work provides deep insights in the ever-diversifying field of metallo-supramolecular chemistry,and will enable us to design more sophisticated assembled structure with desired function.

Fabrication of Neutral Supramolecular Polymeric Films via Post-electropolymerization of Discrete Metallacycles

Self-assembly post-modification has proven to be an efficient strategy to build higher-order supramolecular architectures and functional materials. In this study, we successfully realized the construction＇of a new family of neutral supramolecular polymeric films containing well-defined metallacycles as the main scaffolds through combination Of coordination-driven self-assembly with post-electropolymerization. The obtained neutral polymeric materials were fully characterized by the cyclic voltammogram （CV）, SEM, and TEM. The thickness of the films was able to be well regulated by the number of scanning cycles. Moreover, we found that the shape of the metallacycles and the number of triphenylamine moieties played important roles in the formation of the final polymer films. We believe that the introduction of the neutral metallacycles into the final polymer structures not only enriches the library of supramolecular polymeric films but also provides a new platform to study neutral molecule detection, separation, and capture.

Hierarchical self-assembly of triangular metallodendrimers into the ordered nanostructures

We designed and constructed a new family of 608 dendritic dipyridyl donors, from which two novel triangular metallodendrimers were successfully prepared via coordination-driven self-assembly.Inspired by the existence of multiple intermolecular interactions（e.g., p–p stacking and CH–p interactions） imposed by the DMIP-functionalized poly（benzyl ether） dendrons, their hierarchical selfassembly behaviors were studied in various mixed solvents by using scanning electron microscopy（SEM）. Interestingly, it was found that the morphologies of the obtained metallodendrimers were highly depended on the dendron generation. For example, the first-generation metallodendrimer was able to hierarchically self-assemble into the spherical nanostructures in various mixed solvents. However, the nanofibers were observed for the second-generation metallodendrimer under the similar conditions.Furthermore, the driven force for the formation of such ordered nanostructures was investigated by using1 H NMR and fluorescence spectroscopy.

Our expedition in the construction of fluorescent supramolecular metallacycles

During the past few years, the construction of fluorescent supramolecular metallocycles has attracted extensive attention due to their diverse applications such as sensing, photoelectric devices, and mimicking complicated natural photo-processes. In this review, we will discuss how we entered the field of fluorescent supramolecular metallacycles and what we investigated in this field. The preparation of various fluorescent supramolecular metallacycles and their applications in monitoring the dynamics of coordination-driven self-assembly, sensing, catalysts, and supramolecular gels will be summarized.

Metallacycles,metallacages,and their aggregate/optical behavior

Since the first metallacycle was prepared by Verkade in 1983,various metallacycles and metallacages with controllable nanoscale shapes and sizes have been created by modular design and synthesis,showing unique properties that enable applications in catalysis,sensors,and biomedicine.Everything from their photophysical properties to their antitumor activities and catalysis was found to be influenced by their suprastructures.Thus,it is necessary and helpful to develop a systematic understanding of the relationships among the micro/nanostructures,the resultant photophysical/chemical properties,and the corresponding applications.In this review,we summarized the latest progress in this area in approximately the past 5 years.

Conformational effect on fluorescence emission of tetraphenylethylene-based metallacycles

Herein,we designed and constructed two metallacycles,1 and 2,to illustrate the conformational effect of isomeric AIE fluoropho res on the platfo rm of supramolecular coordination complexe s(SCCs).Specifically,the dangling phenyl rings in TPE units of the metallacycle 1 align completely outside the main cyclic structure,while in the metallacycle 2,these phenyl rings align half inside and half outside.The experimental results showed that two metallacycles exhibited different behaviors in terms of AIE fluorescence and chemical sensing,which could be attributed to the subtle structural difference of the TPE units.This work repre sents the unification of topics such as self-assembly,AIE,and chemical sensing,and further promotes the understanding for the structure-property relationship of isomeric AIE fluorophores.

Fluorescence-resonance energy transfer(FRET)within the fluorescent metallacycles

During past few years,the construction of fluorescent metallacycles featuring the fluorescenceresonance energy transfer behavior has attracted extensive attention due to their diverse applications such as real-time monitoring the dynamics of coordination-driven self-assembly,photoswitching fluorescence-resonance energy transfer,and light-controlled generation of singlet oxygen for cancer therapy.This review focuses on the recent advances on the design principles,preparation methods,optical properties,and the wide applications of fluorescent metallacycles with the FRET property.

Manganese-Fluorouracil Metallodrug Nanotheranostic for MRI-Correlated Drug Release and Enhanced Chemoradiotherapy

For cancer therapy,drug delivery systems are often limited by insufficient drug loading capacity,which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers.Herein,we reported a“one-pot”method for constructing metal(Mn^(2+))–fluorouracil(FU)-coordinated nanotheranostics(Mn-FU)by self-assembly of FU(as bridging ligands)and Mn^(2+)(as metal nodes)through Mn–N/O coordination interactions.Importantly,owing to the effective coordination between Mn and FU,Mn-FU exhibits high drug loading efficacy(47.7 wt%),encapsulation efficacy(82.6%),and relatively large yield(1 g/pot).In acidic tumor microenvironments,efficient release of FU and Mn^(2+)is realized because of nitrogen protonation.The released FU and Mn^(2+)from Mn-FU are used for chemotherapy and turn on magnetic resonance imaging(MRI),respectively,achieving MRI-correlated drug release.After PEG modification,Mn-FU displays high tumor homing ability via enhanced permeability and retention effects and quick renal clearance owing to the disassembly in acidic biological conditions.As a result,Mn-FU substantially enhances the synergistic effects of chemoradiotherapy.Meanwhile,the systemic toxic side effects of free FU-based chemoradiotherapy were greatly reduced through this nanotheranostic.Our strategy offers a facile way to construct metallodrug nanotheranostics for efficient cancer theranostics.