Metal-organic Capsules Research Articles

A Host–Guest Platform for Highly Efficient, Quantitative, and Rapid Detection of Nitroreductase

Nitroreductase (NTR) is an enzyme expressed at an abnormally high level in solid tumors, which is associated with the hypoxia level in tumors. The establishment of a high-performance and convenient fluorescent platform for the fast monitoring of NTR is of pivotal importance. Herein, a novel host–guest complex was created by encapsulating a fluorescent substrate GP-NTR within a metal–organic capsule Zn-MPB that included a NADH mimic for the detection of hypoxia via responding to nitroreductase (NTR) with fast responsiveness and good fluorescence imaging. Notably, the double-substrate process was streamlined to a single–substrate process by the host–guest supramolecular method in the catalytic process of NTR, which enabled the reaction to be independent of the cofactor NADH supply and shortened the distance between the substrate and the active site of NTR. The increasing fluorescence intensity of Zn-MPB⊃GP-NTR exhibits a linear relationship with NTR concentration and shows a fast response toward NTR in solution in tens of seconds. Zn-MPB⊃GP-NTR also displays high sensitivity to NTR with a low detection limit of 6.4 ng/mL. Cells and in vivo studies have confirmed that Zn-MPB⊃GP-NTR could be successfully applied for the fast imaging of NTR in NTR-overexpressed tumor cells and tumor-bearing animals. The host–guest platform not only provides a new avenue for the design and optimization of a fluorescence detection platform for the rapid and quantitative detection of NTR activity, but also offers an imaging tool for the early diagnosis of hypoxia-related tumors.

Nanopore-regulated in situ polymerization for synthesis of homogeneous heparan sulfate with low dispersity

The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.

Triamine and Tetramine Edge-Length Matching Drives Heteroleptic Triangular and Tetragonal Prism Assembly.

Heteroleptic metal-organic capsules, which incorporate more than one type of ligand, can provide enclosed, anisotropic interior cavities for binding low-symmetry molecules of biological and industrial importance. However, the selective self-assembly of a single mixed-ligand architecture, as opposed to the numerous other possible self-assembly outcomes, remains a challenge. Here, we develop a design strategy for the subcomponent self-assembly of heteroleptic metal-organic architectures with anisotropic internal void spaces. Zn6Tet3Tri2 triangular prismatic and Zn8Tet2Tet'4 tetragonal prismatic architectures were prepared through careful matching of the side lengths of the tritopic (Tri) or tetratopic (Tet, Tet') and panels.

Modifying the Oxidative Potentials of Imines in a Dye Loaded Capsule for Photocatalytic Cyclization with Hydrogen Evolution.

Modifying redox potential of substrates and intermediates to balance pairs of redox steps are important stages for multistep photosynthesis but faced marked challenges. Through co-clathration of iridium photosensitizer and imine substrate within one packet of a metal-organic capsule to shift the redox potentials of substrate, herein, we reported a multiphoton enzymatic strategy for the generation of heterocycles by intramolecular C-X hydrogen evolution cross-couplings. The cage facilitated a pre-equilibrium substrate-involving clathrate that cathodic shifts the oxidation potential of the substrate-dye-host ternary complex and configuration inversion of substrate via spatial constraints in the confined space. The new two photon excitation strategy enabled the precise control of the multistep electron transfer between each pair (photosensitizer, substrate and the capsule), endowing the catalytic system proceeding smoothly with an enzymatic fashion. Three kinds of 2-subsituted (-OH, -NH2 , and -SH) imines and N-aryl enamines all give the corresponding cyclization products efficiently under visible light irradiation, demonstrating the promising of the microenvironment driven thermodynamic activation in the host-dye-substrate ternary for synergistic combination of multistep photocatalytic transformations.

Light-Driven Purification of Progesterone from Steroid Mixtures Using a Photoresponsive Metal-Organic Capsule.

Chemical separations are expensive, consuming 10-15% of humanity's global energy budget. Many current separation methods employ thermal energy for distillation, often through the combustion of carbon-containing fuels, or extractions and crystallizations from organic solvents, which must then be discarded or redistilled, with a substantial energetic cost. The direct use of renewable energy sources, such as light, could enable the development of novel separations processes, as is required for the transition away from fossil fuel use. Metal-organic capsules, which can selectively bind molecules from mixtures, can provide the foundation for these novel separations processes. Here we report a tetrahedral metal-organic capsule bearing light-responsive diazo moieties around its metal-ion vertices. This capsule can be used to selectively separate progesterone from a mixture of steroids in a process driven by visible light energy. Our process combines biphasic extraction and selective binding of progesterone with the light-driven release of this molecule in purified form. Ultimately, our process might be adapted to the purifications of the many other fine chemical products that are bound selectively by capsules.

High-order layered self-assembled multicavity metal--organic capsules and anti-cooperative host-multi-guest chemistry.

The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex metal-organic capsules with multiple cavities and achievement of multi-guest encapsulation, and further in-depth comprehension of host-multi-guest recognition remain a great challenge. Just like building LEGO blocks, herein, we have constructed a series of high-order layered metal-organic architectures of generation n (n = 1/2/3/4 is also the number of cavities) by multi-component coordination-driven self-assembly using porphyrin-containing tetrapodal ligands (like plates), multiple parallel-podal ligands (like clamps) and metal ions (like nodes). Importantly, these high-order assembled structures possessed different numbers of rigid and separate cavities formed by overlapped porphyrin planes with specific gaps. The host-guest experiments and convincing characterization proved that these capsules G2-G4 could serve as host structures to achieve multi-guest recognition and unprecedentedly encapsulate up to four C60 molecules. More interestingly, these capsules revealed negative cooperation behavior in the process of multi-guest recognition, which provides a new platform to further study complicated host-multi-guest interaction in the field of supramolecular chemistry.

Redox Triggers Guest Release And Uptake Across A Series of Azopyridine-Based Metal-Organic Capsules.

Precise control over guest release and recapture using external stimuli is a valuable goal, potentially enabling new modes of chemical purification. Including redox moieties within the ligand cores of molecular capsules to trigger the release and uptake of guests has proved effective, but this technique is limited to certain capsules and guests. Herein, we demonstrated the construction of a series of novel metal-organic capsules from ditopic, tritopic and tetratopic ligands respectively, which contain redox-active azo groups coordinated to FeII centers. Compared to their iminopyridine-based analogs, this new class of azopyridine-based capsule possess larger cavities, capable of encapsulating more voluminous guests. Upon reduction of the capsules, their guests are released and may then be re-encapsulated when the capsules are regenerated by oxidation. Since the redox centers are on the ligand arms, they are modular and can be attached to a variety of ligand cores to afford varying and predictable architectures. Our method thus shows promise as a generalized approach for designing redox-controlled guest release and uptake systems. This article is protected by copyright. All rights reserved.

Thermally Tunable Adsorption of Xenon in Crystalline Molecular Sorbent.

The thermostability of encapsulated xenon is investigated in a series of isostructural crystalline sorbents. These sorbents consist of metal-organic capsules, with the general formula of [ConFe4-nL6]4- (n = 1, 2, 3 and 4), where L2- is an organic linker with two sulfonate groups. In the crystalline sorbent, guanidinium cations form H-bond networks with the peripheral sulfonate groups in the solid state and trap xenon in the molecular cavities, which are at least 2.7 times the volume of xenon. When heated, the sorbent retains xenon up to 561 K, i.e., 396 K higher than the boiling point of xenon. Furthermore, the thermostability of trapped xenon can be modulated by varying the ratio of Co:Fe in the crystalline sorbent. Elemental analysis on a single crystal by energy dispersive X-ray spectroscopy confirms the homogeneous distribution of Co and Fe in the sorbent. Structural analyses reveal that the expansion of capsule cavity is proportional to the Co:Fe ratio, with increases of 0.049(1) Å and 6.4(8) Å3 in metal-metal distance and cavity volume, per substitution of Fe by Co center. Steric repulsion between peripheral sulfonate groups is found to render a hypothetical face-centered cubic structure of (C(NH2)3)4[Fe4L6] not accessible, which would have trapped xenon with exceptional thermostability. The stable and tunable trapping of xenon in crystalline sorbents by over-sized molecular cavities suggests a new strategy for separation and storage of xenon, through introduction of kinetic barriers, such as H-bond networks.

Secondary Bracing Ligands Drive Heteroleptic Cuboctahedral PdII12 Cage Formation

The structural complexity of self-assembled metal-organic capsules can be increased by incorporating two or more different ligands into a single discrete product. Such complexity can be useful, by enabling larger, less-symmetrical, or more guests to be bound. Here we describe a rational design strategy for the use of subcomponent self-assembly to selectively prepare a heteroleptic cage with a large cavity volume (2631 Å3) from simple, commercially available starting materials. Our strategy involves the initial isolation of a tris(iminopyridyl) PdII3 complex 1, which reacts with tris(pyridyl)triazine ligand 2 to form a heteroleptic sandwich-like architecture 3. The tris(iminopyridyl) ligand within 3 serves as a "brace" to control the orientations of the labile coordination sites on the PdII centers. Self-assembly of 3 with additional 2 was thus directed to generate a large PdII12 heteroleptic cuboctahedron host. This new cuboctahedron was observed to bind multiple polycyclic aromatic hydrocarbon guests simultaneously.

Modifying Enzymatic Substrate Binding within a Metal-Organic Capsule for Supramolecular Catalysis.

Supramolecular catalysis is established to modify reaction kinetics by substrate encapsulation, but manipulating the thermodynamics of electron-transfer reactions remains unexplored. Herein, we reported a new microenvironment-shielding approach to induce an anodic shift in the redox potentials of hydrazine substrates, reminiscent of the enzymatic activation for N-N bond cleavage within a metal-organic capsule H1. Equipped with the catalytic active cobalt sites and substrate-binding amide groups, H1 encapsulated the hydrazines to form the substrate-involving clathration intermediate, triggering the catalytic reduction N-N bond cleavage when electrons were acquired from the electron donors. Compared with the reduction of free hydrazines, the conceptual molecular confined microenvironment decreases the Gibbs free energy (up to -70 kJ mol-1), which is relevant to the initial electron-transfer reaction. Kinetic experiments demonstrate a Michaelis-Menten mechanism, which involves the formation of the pre-equilibrium of substrate-binding, followed by bond cleavage. Then, the distal N is released as NH3 and the product is squeezed. Integrating fluorescein into H1 enabled the photoreduction of N2H4 with an initial rate of ca. 1530 nmol min-1 into ammonia, comparable to that of natural MoFe proteins; thus, the approach provides an attractive manifold toward mimicking enzymatic activation.

A metal-organic capsule self-assembled by hydrogen bonds for adsorption of methylene blue

ABSTRACT Dyes are a class of hazardous chemicals that can cause harm to the environment and life on earth. However, it remains a huge challenge for the effective removal of the dyes. Herein, a new metal-organic capsule {[Cu(L)(bpy)(H2O)]·H2O}n (1) was synthesised by (4,4’-(((1,3,4-thiadiazole-2,5-diyl)bis(sulfanediyl))bis (methylene)) dibenzoic acid, 2,2’-bipyridine and CuCl2∙2 H2O under solvothermal condition. Interestingly, two inversion asymmetric units are connected by O-H···O and O-H···N to form a centrosymmetric capsule with cavity. The intermolecular interactions were further quantitatively analysed and visualised by the CrystalExplorer 17.5. Notably, complex 1 can effectively adsorb methylene blue (MB), and the adsorption performance is linearly correlated with MB concentration. When the concentration of MB was increased from 10 to 50 mg∙L−1, the adsorption performance of 1 was increased from 17.68 to 66.79 mg∙g−1, while reduced the MB removal efficiency from 88.4% to 66.4%. The adsorption process is suitable for the pseudo-second-order and the Langmuir model. Furthermore, complex 1 showed the good recyclability and stability for at least five runs.

Enzyme Grafting with a Cofactor-Decorated Metal-Organic Capsule for Solar-to-Chemical Conversion.

Semi-artificial approaches to solar-to-chemical conversion can achieve chemical transformations that are beyond the capability of natural enzymes, but face marked challenges to facilitate in vivo cascades, due to their inevitable need for cofactor shuttling and regeneration. Here, we report on an enzyme grafting strategy to build a metal-organic capsule-docking artificial enzyme (metal-organic-enzyme, MOE) that comprised the self-assembly of a cofactor-decorated capsule and the supramolecular enzyme-recognition features between the enzyme scaffold and the capsule to bypass cofactor shuttling and regeneration. The incorporated NADH mimics within the metal-organic capsule interacted with the imine intermediate that formed from the condensation of the amines and the dehydrogenation of alcohol substrates in the microenvironment to form complexes within the capsule and subsequently served as an in situ-generated photoresponsive cofactor. Upon illumination, the photoresponsive cofactor facilitates efficient proton/electron transport between the inner space (supramolecular hydrogenation) and outer space (enzymatic dehydrogenation) of the capsule to dehydrogenize the alcohols and hydrogenize the imine intermediates, respectively, circumventing the conventionally complex multistep cofactor shuttling and regeneration. The semi-artificial enzyme endows the conversion of diverse types of alcohol to amine products in both aqueous/organic solutions and Escherichia coli with high efficiency, offering a wide range of opportunities for sustainable and environmentally friendly biomanufacturing of commodity and fine chemicals.

Light-switched selective catalysis with NADH mimic functionalized metal-organic capsules.

By incorporating an active site model of nicotinamide adenine dinucleotide (NADH) as an electron regulator, a redox-active metal-organic capsule as an efficient photocatalyst was obtained for the light switchable synthesis of a series of aromatic azoxy and amino compounds from their corresponding nitroaromatics under either purple (420 nm) or blue (455 nm) LED light irradiation.

Binding of Dual-Function Hybridized Metal-Organic Capsules to Enzymes for Cascade Catalysis.

The combination of chemo- and biocatalysis for multistep syntheses provides attractive advantages in terms of evolvability, promiscuity, and sustainability striving for desirable catalytic performance. Through the encapsulation of flavin analogues by both NADH and heme mimics codecorated heteroleptic metal–organic capsules, herein, we report a progressive host–guest strategy to imitate cytochrome P450s catalysis for cascade oxidative coupling catalysis. Besides the construction of stable dual-function metal–organic capsules and the modification of cofactor-decorated capsules at the domain of enzymes, this supramolecular strategy involves multistage directional electron flow, affording reactive ferric peroxide species for inducing oxygenation. Under light irradiation, the metal–organic capsule selectively converts stilbene to oxidative coupling products (including 2-oxo-1,2-diphenylethyl formate, 2-alkoxy-1,2-diphenylethanone) in tandem with enzymatic reactions respectively, at the domain of natural enzymes. The ingenious combination of capsules and enzymes with the in situ-regenerated capsule-loaded NADH cofactor promises non-native coupling reactions by forming regional cooperation and division. This abiotic–biotic conjugated host–guest strategy is conducive to the de novo creation of multifunctional components approaching active enzymatic sites for reinforced matter and energy transporting, demonstrating a key role of multicomponent supramolecular catalysts for one-pot integrated catalytic conversions.

Self-assembly of a large, closed capsule reminiscent of protein-cage formation

In this issue of <i>Chem</i>, Nitschke and co-workers report on a new type of tetrahedral cage where, unlike in conventional metal-organic capsules (in which individual ligands define the faces or edges of a polyhedron), each face of the capsule is spanned by three ligand panels, reminiscent of ferritin capsule formation. They achieve this concept through the self-assembly of a simple twisted tetramine subcomponent. Moreover, the resulting large, enclosed cavity is able to accommodate multiple equivalents of large dianions.

Twisted rectangular subunits self-assemble into a ferritin-like capsule

<h2>Summary</h2> The vertices of polyhedral protein capsules are spanned by multiple capsule-forming protein subunits, thus enclosing more volume and larger cargoes than if single proteins connected vertices directly. Application of protein cage design principles to synthetic analogs would allow a given ligand to enclose a greater volume. Here, we report the self-assembly of a simple tetramine subcomponent into a tetrahedral metal-organic capsule, with each face of the capsule composed of three ligand panels. The edges of the capsule are 31.8 Å in length—double the distance that can be spanned by a single subcomponent. The self-assembly rules followed by this system are programmed into the tetramine—it twists out of planarity in its lowest-energy configuration, thus favoring the large capsule over a simpler cube-like architecture. Unlike other large metal-organic capsules, the cavity of this new capsule is enclosed, and the structure was observed to bind large dianionic guests.

Encapsulating electron-deficient dyes into metal-organic capsules to achieve high reduction potentials.

The design of artificial supramolecular systems that mimic the structure and functionality of natural enzymes to achieve efficient chemical conversions is a promising subject. In this work, we assembled a novel metal-organic capsule from electron-rich dyes, polyaniline compounds, as ligands by a subcomponent self-assembly strategy. By encapsulating electron-deficient dyes, anthraquinone or 9,10-dicyanoanthracene, into electron-rich pseudo-cubic capsules, we successfully constructed an artificial enzyme-mimicking supramolecular system for the efficient photocatalytic reduction of aryl chlorides with high reduction potentials (Ered < -2.0 V) via multiphoton excitation. Within the confined space of the host, the electron-deficient dyes were forced to come into contact intimately with the electron-rich host walls, which facilitates the photoinduced electron transfer process. Moreover, we achieved quantitative yields in the photocatalytic reduction reaction under mild conditions within 30 minutes, which was rarely reported in the previous literature in terms of reaction efficiency. This study provides a general and valuable strategy for activating inert substrates, which may have potential applications in solar energy conversion and enzyme-mimicking catalysis in the chemical industry.

Frontispiece: Self‐Assembly of a Semiconductive and Photoactive Heterobimetallic Metal–Organic Capsule

Metal–Organic Capsules A mixed Fe3+/Co2+-seamed capsule comprising multiple heterometallic metal–metal interactions is presented by Sisi Feng, Jerry L. Atwood et al. in their Communication on page 10516. This novel capsule displays unexpected semiconducting properties.

Frontispiz: Self‐Assembly of a Semiconductive and Photoactive Heterobimetallic Metal–Organic Capsule

Metallorganische Kapseln Eine Fe3+/Co2+-Kapsel mit heterometallischen Metall-Metall-Wechselwirkungen wird von Jerry L. Atwood et al. in der Zuschrift auf S. 10610 vorgestellt. Diese neuartige Kapsel zeigt unerwartete Halbleitereigenschaften.

Self‐Assembly of a Semiconductive and Photoactive Heterobimetallic Metal–Organic Capsule

AbstractWe report the synthesis of a novel metal–organic capsule constructed from six pyrogallol[4]arene macrocycles, which are switched together by 16 FeIII and 16 CoII ions. This supramolecular structure is the first instance of a spheroidal heterometallic nanocage assembled through a one‐step metal–ligand coordination approach. This new assembly also demonstrates an important proof of concept through the formation of multiple heterometallic metal–metal interactions within the capsule framework. Photophysical and electrochemical studies of self‐assembled capsule films indicate their potential as semiconductors. These materials display unexpected photoelectric conversion properties, thus representing an emergent phenomenon in discrete metal–organic supramolecular assemblies.