Codelivery of Dual Gases with Metal-Organic Supramolecular Cage-Based Microenvironment-Responsive Nanomedicine for Atherosclerosis Therapy.

Atherosclerosis (AS) is a common cause of coronary heart disease and stroke. The delivery of exogenous H2S and in situ production of O2 within atherosclerotic plaques can help suppress inflammatory cell infiltration and alleviate disease progression. However, the uncontrolled release of gas donors hinders achieving effective drug concentrations and causes toxic effects. Herein, diallyl trisulfide (DATS)-loaded metal-organic cage (MOC)-68-doped MnO2 nanoparticles are developed as a microenvironment-responsive nanodrug with the capacity for the in situ co-delivery of H2S and O2 to inflammatory cells within plaques. This nanomedicine exhibited excellent monodispersity and stability and protected DATS from degradation in the circulation. In vitro studies showed that the nanomedicine reduced macrophage polarization toward an inflammatory phenotype and inhibited the formation of foam cells, while suppressing the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin-1ß. In a mouse model of ApoE-/- genotype, the nanomedicine reduces the plaque burden, inflammatory infiltration, and hypoxic conditions within the plaques. Furthermore, the treatment process and therapeutic effects can be monitored by magnetic resonance image (MRI), in real time upon Mn2+ release from the acidic- and H2O2- microenvironment-responsive MnO2 nanoparticles. The DATS-loaded MOC-68-doped MnO2-based nanodrug holds great promise as a novel theranostic platform for AS.

A Chiral [2+3] Covalent Organic Cage Based on 1,1'-Bi-2-naphthol (BINOL) Units.

A [2+3] chiral covalent organic cage is produced through a dynamic covalent chemistry approach by mixing two readily available building units, viz. an enantiopure 3,3'-diformyl 2,2'-BINOL compound (A) with a triamino spacer (B). The two enantiomeric (R,R,R) and (S,S,S) forms of the cage C are formed nearly quantitatively thanks to the reversibility of the imine linkage. The X-ray diffraction analysis of cage (S,S,S)-C highlights that the six OH functions of the BINOL fragments are positioned inside the cage cavity. Upon reduction of the imine bonds of cage C, the amine cage D is obtained. The ability of the cage D to host the 1-phenylethylammonium cation (EH+) as a guest is evaluated through UV, CD and DOSY NMR studies. A higher binding constant for (R)-EH+ cation (Ka=1.7 106±10 % M-1) related to (S)-EH+ (Ka=0.9 106±10 % M-1) is determined in the presence of the (R,R,R)-D cage. This enantiopreference is in close agreement with molecular dynamics simulation.

Stabilization of Lantern-Type Metal-Organic Cages (MOCs) by Protective Control of Ligand Exchange Rates.

Self-assembling systems in nature display remarkable complexity with assemblies of different sub-units to generate functional species. Synthetic analogues of such systems are a challenge, often requiring the ability to bias distributions that are under thermodynamic assembly control. Using lantern-type MOCs (metal-organic cages) as a prototypical self-assembling system, herein we explore the role that steric bulk plays in controlling the exchange rate of ligands in paddlewheel-based assemblies, and thus the stability of cages, in competitive self-assembling scenarios. The effective lifetime of the lantern-type MOCs varies over an order of magnitude depending on the steric bulk proximal to the metal nodes with lifetimes of the cages ranging from tens of minutes to several hours. The bulk of the coordinating solvents likewise reduces the rate of ligand exchange, and thus yields longer-lived species. Understanding this subtle effect has implications for controlling the stability of complex assemblies in competitive environments with implications for guest release and application.

Heterometallic-organic cages with customized cavities: constructed by bottom-up step-wise coordination-driven self-assembly.

accurately synthesizing coordination-driven metal-organic cages with customized shape and cavity remain a great challenge for chemists. In this work, a bottom-up step-wise coordination-driven self-assembly approach was put forward. Employing this strategy, three terpyridyl heterometallic-organic truncated tetrahedral cages with different sizes and cavity were precisely synthesized. Firstly, the coordination of tripodal organic ligands with Ru2+ afforded dendritic metal-organic ligands L1-L3. Then the Ru building blocks complexed with Fe2+ and shrunk to form the desired heterometallic-organic cages (C1-C3). These discrete heterometallic-organic supramolecular cages were fully characterized and displayed the large and open cavities varied from 7205 Å3 to 9384 Å3. Notably, these cages could not be directly constructed by single-step assembly process using initial organic ligands or dimeric metal-organic ligands, indicative of the irreplaceability of a bottom-up step-wise assembly strategy for size-customized architectures. This work paves a new way for precisely constructing metal-organic cages with well-defined cavities.

Covalent Post-Synthetic Modification of Metal-Organic Cages: Concepts and Recent Progress.

Metal-organic cages (MOCs) are supramolecular coordination complexes that have internal cavities for hosting guest molecules and exhibiting various properties. However, the functions of MOCs are limited by the choice of the building blocks. Post-synthetic modification (PSM) is a technique that can introduce new functional groups and replace existing ones on the MOCs without changing their geometry. Among many PSM methods, covalent PSM is a promising approach to modify MOCs with tailored structures and functions. Covalent PSM can be applied to either the internal cavity or the external surface of the MOCs, depending on the functionality expected to be customized. However, there are still some challenges and limitations in the field of covalent PSM of MOCs, such as the balance between the stability of MOCs and the harshness of organic reactions involved in covalent PSMs. This concept article introduces the organic reaction types involved in covalent PSM of MOCs, their new applications after modification, and summarizes and provides an outlook of this research field.

Cage-by-cage supramolecular polymerization via panel-decorated triphenylphosphine organic cage.

Significant efforts have been dedicated to designing porous organic cage compounds with geometric complexity and topological diversity. However, the use of these cage molecules as premade building units for constructing infinite cage-based superstructures remains unexplored. Here, we report the use of a panel-decorated phosphine organic cage as a special monomer to achieve supramolecular polymerization, resulting in cage-by-cage noncovalent polymers through the synergy of metal-coordination and intercageπ-πdimerization. At a monomer concentration of 122 mM, the average degree of polymerization reaches 17, corresponding to a molecular weight of 26 kDa. The obtained cage-based supramolecular polymers can further hierarchically self-assemble into vesicular morphologies or one-dimensional nanofiber architectures. Selective control over the cosolvents can regulate their structural hierarchy and assembled morphology. This approach paves a new way for the construction of cage-based hierarchical assemblies and materials.

Crystalline Porous Organic Cage Membranes Constructed Using Fortified Intermolecular Interactions for Molecular Sieving.

Among the various types of materials with intrinsic porosity, porous organic cages (POCs) are distinctive as discrete molecules that possess intrinsic cavities and extrinsic channels capable of facilitating molecular sieving. However, the fabrication of POC membranes remains highly challenging due to the weak noncovalent intermolecular interactions and most reported POCs are powders. In this study, we constructed crystalline free-standing porous organic cage membranes by fortifying intermolecular interactions through the induction of intramolecular hydrogen bonds, which was confirmed by single-crystal X-ray analysis. To elucidate the driving forces behind, a series of terephthaldehyde building blocks containing different substitutions were reacted with flexible triamine under different conditions via interfacial polymerization (IP). Furthermore, density functional theory (DFT) calculations suggest that intramolecular hydrogen bonding can significantly boost the intermolecular interactions. The resulting membranes exhibited fast solvent permeance and high rejection of dyes not only in water, but also in organic solvents. In addition, the membrane demonstrated excellent performance in precise molecular sieving in organic solvents. This work opens an avenue to designing and fabricating free-standing membranes composed of porous organic materials for efficient molecular sieving.

Porous Organic Cage as an Efficient Platform for Industrial Radioactive Iodine Capture.

Herein, we firstly develop porous organic cage (POC) as an efficient platform for highly effective radioactive iodine capture under industrial operating conditions (typically ≥150 °C), ≤150 ppmv of I2). Due to the highly dispersed and readily accessible binding sites as well as sufficient accommodating space, the constructed NKPOC-DT-(I-) (NKPOC=Nankai porous organic cage) demonstrates a record-high I2 uptake capacity of 48.35 wt % and extraordinary adsorption capacity of unit ionic site (~1.62) at 150 °C and 150 ppmv of I2. The I2 capacity is 3.5, 1.6, and 1.3 times higher than industrial silver-based adsorbents Ag@MOR and benchmark materials of TGDM and 4F-iCOF-TpBpy-I- under the same conditions. Furthermore, NKPOC-DT-(I-)Me exhibits remarkable adsorption kinetics (k1=0.013 min-1), which is 1.2 and 1.6 times higher than TGDM and 4F-iCOF-TpBpy-I- under the identical conditions. NKPOC-DT-(I-)Me thus sets a new benchmark for industrial radioactive I2 adsorbents. This work not only provides a new insight for effectively enhancing the adsorption capacity of unit functional sites, but also advances POC as an efficient platform for radioiodine capture in industry.

Artificial Photosynthetic Cell with Molecular Biomimetic Thylakoid.

The construction of solar-to-chemical conversion system by mimicking the photosynthetic network of the chloroplast holds great promise on efficient solar energy utilization. We developed an artificial photosynthetic cell (APC) based on molecular biomimetic thylakoid (CoTPP-FePy) to split water into hydrogen and oxygen (H2 and O2) at low driving voltage (1.1 V) and neutral condition (pH≈7). The CoTPP-FePy can emulate the light reaction in thylakoids to produce O2 by coupling light harvesting, photocatalysis, and electron/energy storage (FeIII/FeII-Py). Subsequently, a membrane electrode assembly (MEA) were employed to simulate the dark reaction, wherein the proton, electron and energy generated by the light reaction can drive the H2 producing process. By a temporally and spatially coupling of the light and dark reactions, the resulting APC achieved a solar conversion efficiency of 3.1%, exceeding that of natural photosynthetic systems and demonstrating the potential of artificial photosynthesis.

Anion Modulation of Ag-Imidazole Cuboctahedral Cage Microenvironments for Efficient Electrocatalytic CO2 Reduction.

How to achieve CO2 electroreduction in high efficiency is a current challenge with the mechanism not well understood yet. The metal-organic cages with multiple metal sites, tunable active centers, and well-defined microenvironments may provide a promising catalyst model. Here, we report self-assembly of Ag4L4 type cuboctahedral cages from coordination dynamic Ag+ ion and triangular imidazolyl ligand 1,3,5-tris(1-benzylbenzimidazol-2-yl) benzene (Ag-MOC-X, X=NO3, ClO4, BF4) via anion template effect. Notably, Ag-MOC-NO3 achieves the highest CO faradaic efficiency in pH-universal electrolytes of 86.1 % (acidic), 94.1 % (neutral) and 95.3 % (alkaline), much higher than those of Ag-MOC-ClO4 and Ag-MOC-BF4 with just different counter anions. In situ attenuated total reflection Fourier transform infrared spectroscopy observes formation of vital intermediate *COOH for CO2-to-CO conversion. The density functional theory calculations suggest that the adsorption of CO2 on unsaturated Ag-site is stabilized by C-H⋅⋅⋅O hydrogen-bonding of CO2 in a microenvironment surrounded by three benzimidazole rings, and the activation of CO2 is dependent on the coordination dynamics of Ag-centers modulated by the hosted anions through Ag⋅⋅⋅X interactions. This work offers a supramolecular electrocatalytic strategy based on Ag-coordination geometry and host-guest interaction regulation of MOCs as high-efficient electrocatalysts for CO2 reduction to CO which is a key intermediate in chemical industry process.

Host-Guest Approach to Promoting Photocatalysis Based on Consecutive Photo-Induced Electron-Transfer Processes via Efficient Förster Resonance Energy Transfer.

Supramolecular artificial light-harvesting system with highly efficient host-guest energy transfer pathway provides an ideal platform for optimizing the photochemistry process. The consecutive photo-induced electron transfer (conPET) process overcomes the energy limitation of visible-light photocatalysis, but is often compromised by mismatching between the absorption of ground state dye and its radical, weakening the efficiency of photoredox reaction. By encapsulating a conPET photocatalyst rhodamine 6G into metal-organic cage, the supramolecular approach was undertaken to tackle the intrinsic difficulty of matching the light absorption of photoexcitation between rhodamine 6G and its radical. The highly efficient Förster resonance energy transfer from the photoexcited cage to rhodamine 6G forced by host-guest encapsulation facilitates the conPET process for the single-wavelength light-driven activation of aryl halides by stabilizing and accelerating the production and accumulation of the rhodamine 6G radical intermediate. The tunable and flexible nature of the supramolecular host-guest complex renders the cage-based encapsulation strategy promising for the development of ideal photocatalysts toward the better utilization of solar energy.

Integrated Anionic Zirconium-Organic Cage and Cationic Boron-Imidazolate Cage for Synergetic Optical Limiting.

Making oppositely charged metal-organic cages (MOCs) into a tightly ordered structure may bring interesting functions. Herein, we report a novel structure composed of anionic (Zr4 L6 )8- (L=embonate) tetrahedral cages and in situ-formed cationic [Zn4 (Bim)4 ]4+ (Bim=[BH(im)3 ]- ; im=imidazole) cubic cages. Chiral transfer is observed from enantiopure (Zr4 L6 )8- cage to enantiopure [Zn4 (Bim)4 ]4+ cage. A pair of enantiomers (PTC-373(Δ) and PTC-373(Λ)) are formed. PTC-373 exhibits high chemical and thermal stabilities, affording an interesting single-crystal-to-single-crystal transformation. More importantly, the combination of ionic pair cages significantly enhances its third-order nonlinear optical property, and its thin-film exhibits an excellent optical limiting effect.

Single Crystals of Insoluble Porous Salicylimine Cages.

Porous organic cages (POCs) are meanwhile an established class of porous materials. Most of them are soluble to a certain extend and thus processable in or from solution. However, a few of larger salicylimine cages were reported to be insoluble in any organic solvents and thus characterized as amorphous materials. These cages were now synthesized as single-crystalline materials to get insight into packing motifs and preferred intermolecular interactions. Furthermore, the pairs of crystalline and amorphous materials for each cage allowed to compare their gas-sorption properties in both morphological states.

Tailored Water-Soluble Covalent Organic Cages for Encapsulation of Pyrene and Information Encryption.

Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.

Preparation of Chiral Porous Organic Cage Clicked Chiral Stationary Phase for HPLC Enantioseparation.

Porous organic cages (POCs) are a new subclass of porous materials, which are constructed from discrete cage molecules with permanent cavities via weak intermolecular forces. In this study, a novel chiral stationary phase (CSP) has been prepared by chemically binding a [4 + 6]-type chiral POC (C120H96N12O4) with thiol-functionalized silica gel using a thiol-ene click reaction and applied to HPLC separations. The column packed with this CSP presented good separation capability for chiral compounds and positional isomers. Thirteen racemates have been enantioseparated on this column, including alcohols, diols, ketones, amines, epoxides, and organic acids. Upon comparison with a previously reported chiral POC NC1-R-based column, commercial Chiralpak AD-H, and Chiralcel OD-H columns, this column is complementary to these three columns in terms of its enantiomeric separation; and can also separate some racemic compounds that cannot be separated by the three columns. In addition, eight positional isomers (iodoaniline, bromoaniline, chloroaniline, dibromobenzene, dichlorobenzene, toluidine, nitrobromobenzene, and nitroaniline) have also been separated. The influences of the injection weight and column temperature on separation have been explored. After the column has undergone multiple injections, the relative standard deviations (RSDs) for the retention time and selectivity were below 1.0 and 1.5%, respectively, indicating the good reproducibility and stability of the column for separation. This work demonstrates that POCs are promising materials for HPLC separation.

Capture of Singlet Oxygen Modulates Host-Guest Behavior of Coordination Cages.

The anthracene panels of two tetrahedral MII 4 L6 cages, where MII =CoII or FeII , were found to react with photogenerated singlet oxygen (1 O2 ) in a hetero-Diels-Alder reaction. ESI-MS analysis showed the cobalt(II) cages to undergo complete transformation of all anthracene panels into endoperoxides, whereas the iron(II) congeners underwent incomplete conversion. The reaction was found to be partially reversible in the case of the 1-FeII cage. The dioxygen-cage cycloadducts were found to bind a set of guest molecules more weakly than the parent cages, with affinity dropping by more than two orders of magnitude in some cases. The light-driven cycloaddition reaction between cage and 1 O2 thus served as a stimulus for guest release and reuptake.

Supramolecular Self-Assembly as a Tool To Preserve the Electronic Purity of Perylene Diimide Chromophores.

Organic semiconductors are promising for efficient, printable optoelectronics. However, strong excited-state quenching due to uncontrolled aggregation limits their use in devices. We report on the self-assembly of a supramolecular pseudo-cube formed from six perylene diimides (PDIs). The rigid, shape-persistent cage sets the distance and orientation of the PDIs and suppresses intramolecular rotations and vibrations, leading to non-aggregated, monomer-like properties in solution and the solid state, in contrast to the fast fluorescence quenching in the free ligand. The stabilized excited state and electronic purity in the cage enables the observation of delayed fluorescence due to a bright excited multimer, acting as excited-state reservoir in a rare case of benign inter-chromophore interactions in the cage. We show that self-assembly provides a powerful tool for retaining and controlling the electronic properties of chromophores, and to bring molecular electronics devices within reach.

Supramolecular Enhancement of Electrochemical Nitrate Reduction Catalyzed by Cobalt Porphyrin Organic Cages for Ammonia Electrosynthesis in Water.

The electrochemical nitrate (NO3 - ) reduction reaction (NO3 RR) to ammonia (NH3 ) represents a sustainable approach for denitrification to balance global nitrogen cycles and an alternative to traditional thermal Haber-Bosch processes. Here, we present a supramolecular strategy for promoting NH3 production in water from NO3 RR by integrating two-dimensional (2D) molecular cobalt porphyrin (CoTPP) units into a three-dimensional (3D) porous organic cage architecture. The porphyrin box CoPB-C8 enhances electrochemical active site exposure, facilitates substrate-catalyst interactions, and improves catalyst stability, leading to turnover numbers and frequencies for NH3 production exceeding 200,000 and 56 s-1 , respectively. These values represent a 15-fold increase in NO3 RR activity and 200-mV improvement in overpotential for the 3D CoPB-C8 box structure compared to its 2D CoTPP counterpart. Synthetic tuning of peripheral alkyl substituents highlights the importance of supramolecular porosity and cavity size on electrochemical NO3 RR activity. These findings establish the incorporation of 2D molecular units into 3D confined space microenvironments as an effective supramolecular design strategy for enhancing electrocatalysis.

A Self-Assembled Capsule for Propylene/Propane Separation.

The development of energy-saving technology for the efficient separation of olefin and paraffin is highly important for the chemical industry. Herein, we report a self-assembled Fe4 L6 capsule containing a hydrophobic cavity, which can be used to encapsulate and separate propylene/propane. The successful encapsulation of propylene and propane by the Fe4 L6 cage in a water solution was documented by NMR spectroscopy. The binding constants K for the Fe4 L6 cage toward propylene and propane were determined to be (5.0±0.1)×103  M-1 and (2.1±0.7)×104  M-1 in D2 O at 25 °C, respectively. Experiments and theoretical studies revealed that the cage exhibited multiple weak interactions with propylene and propane. The polymer-grade propylene (>99.5 %) can be obtained from a mixture of propylene and propane by using the Fe4 L6 cage as a separation material in a U-shaped glass tube. This work provides a new strategy for the separation of olefin/paraffin.

Tailor-Made Pdn L2n Metal-Organic Cages through Covalent Post-Synthetic Modification.

Post-synthetic modification (PSM) is an effective approach for the tailored functionalization of metal-organic architectures, but its generalizability remains challenging. Herein we report a general covalent PSM strategy to functionalize Pdn L2n metal-organic cages (MOCs, n=2, 12) through an efficient Diels-Alder cycloaddition between peripheral anthracene substituents and various functional motifs bearing a maleimide group. As expected, the solubility of functionalized Pd12 L24 in common solvents can be greatly improved. Interestingly, concentration-dependent circular dichroism and aggregation-induced emission are achieved with chiral binaphthol (BINOL)- and tetraphenylethylene-modified Pd12 L24 , respectively. Furthermore, Pd12 L24 can be introduced with two different functional groups (e.g., chiral BINOL and achiral pyrene) through a step-by-step PSM route to obtain chirality-induced circularly polarized luminescence. Moreover, similar results are readily observed with a smaller Pd2 L4 system.