Stepwise Protonation of Three-Dimensional Covalent Organic Frameworks for Enhancing Hydrogen Peroxide Photosynthesis.

Three-dimensional covalent organic frameworks (3D COFs), recognized for their tailorable structures and accessible active sites, offer a promising platform for developing advanced photocatalysts. However, the difficulty in the synthesis and functionalization of 3D COFs hinders their further development. In this study, we present a series of 3D-bcu-COFs with 8 connected porphyrin units linked by linear linkers through imine bonds as a versatile platform for photocatalyst design. The photoresponse of 3D-bcu-COFs was initially modulated by functionalizing linear linkers with benzo-thiadiazole or benzo-selenadiazole groups. Furthermore, taking advantage of the well-exposed porphyrin and imine sites in 3D-bcu-COFs, their photocatalytic activity was optimized by stepwise protonation of imine bonds and porphyrin centers. The dual protonated COF with benzo-selenadiazole groups exhibited enhanced charge separation, leading to an increased photocatalytic H2O2 production under visible light. This enhancement demonstrates the combined benefits of linker functionalization and stepwise protonation on photocatalytic efficiency.

Bimodal Oxidation Electrochemiluminescence Mechanism of Coreactant-Embedded Covalent Organic Frameworks via Postsynthetic Modification.

Electrochemiluminescence (ECL) efficiency is determined by charge transfer between coreactants and emitters in coreactant systems, which are usually limited by their slow intermolecular charge transfer. In this study, a covalent organic framework (COF) with aldehyde residue was synthesized, and then coreactants were covalently integrated into the skeleton through the postsynthetic modification strategy, resulting in a crystalline coreactant-embedded COF nanoemitter (C-COF). Compared to the pristine COF with an equivalent external coreactant, C-COF exhibited an extraordinary 1008-fold enhancement of ECL intensity due to the rapid intrareticular charge transfer. Significantly, with the pH increase, C-COF shows protonation-induced ECL enhancement for the first ECL peaked at +1.1 V and an opposite trend for the second ECL at +1.4 V, which were attributed to the antedating oxidation of coreactant in framework and COF self-oxidation, respectively. The resulting bimodal oxidation ECL mechanism was rationalized by spectral characterization and density functional theory calculations. The postsynthetic coreactant-embedded nanoemitters present innovative and universal avenues for advancing ECL systems.

Ultrastable Anion Radicals in Ligand-Dimerized Frameworks for Self-Accumulated Electrochemiluminescence.

Electrochemiluminescence (ECL) is a light-emitting process that occurs via an annihilation reaction among energetic radical intermediates, whose stabilities determine the ECL efficiency. In this study, a ligand-dimerized metal-organic framework (MOF) with ultrastable anion radical is designed as an efficient nanoemitter for self-accumulated ECL. Due to the nonplanar structure of perylene diimide (PDI) derivate, two PDI ligands in the framework form a J-dimer unit with a vertical distance of ∼5.74 Å. In cathodic scanning, the ligand-dimerized MOF demonstrates three-step ECL emissions with a gradual increase in ECL intensity. Unlike the decrease in the PDI ligand, the self-accumulated ECL of the MOF was observed with 16.8-fold enhancement due to the excellent stability of radical intermediates in frameworks. Electron paramagnetic resonance demonstrated the ultrastability of free radicals in the designed frameworks, with 82.2% remaining even after one month of storage. Density functional theory calculations supported that PDI dimerization was energetically favorable upon successive electron injection. Moreover, the ECL wavelength is 610 nm, corresponding to the emission of excited dimers. The radical-stabilized reticular nanoemitters open up a new platform for decoding the fundamentals of self-accumulated ECL systems.

Reticular Electrochemiluminescence Nanoemitters: Structural Design and Enhancement Mechanism.

ConspectusElectrochemiluminescence (ECL) is a powerful transduction technique, which depends critically on the formation of the excited emitter through the charge transfer between the electrochemical reaction intermediates of the emitter and the co-reactant/emitter. The exploration of ECL mechanisms for conventional nanoemitters is limited due to the uncontrollable charge transfer process. With the development of molecular nanocrystals, reticular structures such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) have been utilized as atomically precise semiconducting materials. The long-range order in crystalline frameworks and the tunable coupling among building blocks promote the quick development of electrically conductive frameworks. Especially, the reticular charge transfer can be regulated by both interlayer electron coupling and intralayer topology-templated conjugation. By modulating intramolecular or intermolecular charge mobility, reticular structures could serve as promising candidates for enhancing ECL. Thus, reticular crystalline nanoemitters with different topologies provide a confined platform to understand ECL fundamentals for designing next-generation ECL devices.Aiming at exploring the mechanism of ECL emission, our group has developed a series of ECL nanoemitters as well as enhancement strategies of ECL emission in the past 20 years. A series of water-soluble ligand-capped quantum dots were introduced as ECL nanoemitters to create sensitive analytical methods for detecting and tracing biomarkers. The functionalized polymer dots were also designed as ECL nanoemitters for imaging of membrane proteins with signal transduction strategies of dual resonance energy transfer and dual intramolecular electron transfer. To decode the ECL fundamental and enhancement mechanisms, an electroactive MOF with accurate molecular structure was first constructed with two redox ligands as a highly crystallized ECL nanoemitter in aqueous medium. Through the mixed-ligand approach, luminophores and co-reactants were integrated into one MOF structure for self-enhanced ECL. Furthermore, several donor-acceptor COFs were developed as efficient ECL nanoemitters with tunable intrareticular charge transfer. The atomically precise structure of conductive frameworks established clear correlations between the structure and charge transport in these materials. Therefore, reticular materials as crystalline ECL nanoemitters have demonstrated both proof of concept and mechanistic innovation.In this Account, taking advantage of reticular materials with accurate molecular structure, we survey the design of the electroactive reticular materials including MOFs and COFs as crystalline ECL nanoemitters at the molecular level. The enhancement mechanisms of ECL emission of various topology frameworks are discussed via the regulation of reticular energy transfer and charge transfer and the accumulation of anion/cation radicals. Our perspective on the reticular ECL nanoemitters is also discussed. This Account provides a new avenue for designing molecular crystalline ECL nanoemitters and decoding the fundamentals of ECL detection methods.

A Versatile G-Quadruplex (G4)-Coated Upconverted Metal-Organic Framework for Hypoxic Tumor Therapy.

Given the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. The most efficient strategies combine several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Herein, the G-quadruplex (G4)-forming sequence AS1411-A (d[(G2 T)4 TG(TG2 )4 A]) is used for both its anti-tumor and biocatalytic properties when combined with hemin, increasing the production of O2 ca. two-fold as compared to the parent AS1411 sequence. The AS1411-A/hemin complex (GH) is grafted on the surface and pores of a core-shell upconverted metal-organic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibits enhanced colloidal stability, increased tumor cell targeting and improved O2 production (8.5-fold) in situ. When irradiated by near-infrared (NIR) light, the UMGH antitumor properties are bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1 O2 ). Combined with the antiproliferative activity of AS1411-A, this novel approach lays the foundation for a new type of G4-based nanomedicine.

Postsynthetic Annulation of Three-Dimensional Covalent Organic Frameworks for Boosting CO2 Photoreduction.

Three-dimensional covalent organic frameworks (3D COFs), with interconnected pores and exposed functional groups, provide new opportunities for the design of advanced functional materials through postsynthetic modification. Herein, we demonstrate the successful postsynthetic annulation of 3D COFs to construct efficient CO2 reduction photocatalysts. Two 3D COFs, NJU-318 and NJU-319Fe, were initially constructed by connecting hexaphenyl-triphenylene units with pyrene- or Fe-porphyrin-based linkers. Subsequently, the hexaphenyl-triphenylene moieties within the COFs were postsynthetically transformed into π-conjugated hexabenzo-trinaphthylene (pNJU-318 and pNJU-319Fe) to enhance visible light absorption and CO2 photoreduction activity. The optimized photocatalyst, pNJU-319Fe, shows a CO yield of 688 µmol g-1, representing a 2.5-fold increase compared to that of unmodified NJU-319Fe. Notably, the direct synthesis of hexabenzo-trinaphthylene-based COF catalysts was unsuccessful due to the low solubility of conjugated linkers. This study not only provides an effective method to construct photocatalysts but also highlights the unlimited tunability of 3D COFs through structural design and postsynthetic modification.

A Self-Templated Design Approach toward Multivariate Metal-Organic Frameworks for Enhanced Oxygen Evolution.

Multivariate metal-organic framework (MOF) is an ideal electrocatalytic material due to the synergistic effect of multiple metal active sites. In this study, a series of ternary M-NiMOF (M = Co, Cu) through a simple self-templated strategy that the Co/Cu MOF isomorphically grows in situ on the surface of NiMOF is designed. Owing to the electron rearrange of adjacent metals, the ternary CoCu-NiMOFs demonstrate the improved intrinsic electrocatalytic activity. At optimized conditions, the ternary Co3 Cu-Ni2 MOFs nanosheets give the excellent oxygen evolution reaction (OER) performance of current density of 10 mA cm-2 at low overpotential of 288 mV with a Tafel slope of 87 mV dec-1 , which is superior to that of bimetallic nanosheet and ternary microflowers. The low free energy change of potential-determining step identifies that the OER process is favorable at Cu-Co concerted sites along with strong synergistic effect of Ni nodes. Partially oxidized metal sites also reduce the electron density, thus accelerating the OER catalytic rate. The self-templated strategy provides a universal tool to design multivariate MOF electrocatalysts for highly efficient energy transduction.

Electron Donor Coordinated Metal-Organic Framework to Enhance Photoelectrochemical Performance.

To enhance photoelectrochemical (PEC) performance, additional electron donor/acceptor is generally required to inhibit the electron-hole recombination. However, the enhancement is limited due to the long-distance diffusion. Herein a self-supplying electron strategy is designed for PEC enhancement by coordinating an electron donor 1.4-diazabicyclo[2.2.2]octane (Dabco) in metal-organic framework (MOF). The intrareticular photoelectron transfer mechanism in mixed-ligand MOF (m-MOF) is experimentally revealed and verified by density functional theory calculations. The presence of Dabco efficiently inhibits the electron-hole recombination due to the self-supplying electrons and longer electron lifetime in the framework, and thus leads to 23.2-fold enhancement of photocurrent. As proof of concept, a simple PEC method is constructed with the designed m-MOF to demonstrate its application in sensitive bioanalysis. This work provides a new avenue for improving the PEC performance of nanomaterials.

Efficient Biocatalytic System for Biosensing by Combining Metal-Organic Framework (MOF)-Based Nanozymes and G-Quadruplex (G4)-DNAzymes.

A high catalytic efficiency associated with a robust chemical structure are among the ultimate goals when developing new biocatalytic systems for biosensing applications. To get ever closer to these goals, we report here on a combination of metal-organic framework (MOF)-based nanozymes and a G-quadruplex (G4)-based catalytic system known as G4-DNAzyme. This approach aims at combining the advantages of both partners (chiefly, the robustness of the former and the modularity of the latter). To this end, we used MIL-53(Fe) MOF and linked it covalently to a G4-forming sequence (F3TC), itself covalently linked to its cofactor hemin. The resulting complex (referred to as MIL-53(Fe)/G4-hemin) exhibited exquisite peroxidase-mimicking oxidation activity and an excellent robustness (being stored in water for weeks). These properties were exploited to devise a new biosensing system based on a cascade of reactions catalyzed by the nanozyme (ABTS oxidation) and an enzyme, the alkaline phosphatase (or ALP, ascorbic acid 2-phosphate dephosphorylation). The product of the latter poisoning the former, we thus designed a biosensor for ALP (a marker of bone diseases and cancers), with a very low limit of detection (LOD, 0.02 U L-1), which is operative in human plasma samples.

Framework-promoted charge transfer for highly selective photoelectrochemical biosensing of dopamine.

Traditional photoelectrochemical (PEC) systems with inorganic semiconductors as photoactive materials generally involve effortless recombination of electron-hole pairs, which greatly limit the detection sensitivity. The arrangement of multiple components with tunable bandgaps provides an effective way to accelerate charge transfer. In this work, a framework material with adjustable structure was used to promote the charge transfer in the PEC process. The framework was constructed with 9,10-di(p-carboxyphenyl)anthracene (DPA) ligands as the light collector to coordinate with Zn2+ nodes, which formed an electronegative metal-organic framework (ZnMOF), and showed good conductivity and PEC performance due to the π-π stacking of DPA and the intrareticular charge transfer. Based on the band and charge matching of dopamine (DA) with ZnMOF, the ZnMOF modified electrode as a biosensor showed excellent PEC response to DA with good selectivity, thus realized sensitive detection of DA ranging from 0.03 to 10 µM with a detection limit of 17.7 nM. The biosensor could be used to monitor the release of DA from PC12 cells and evaluate the stimulation of K+ to DA release. The conductive framework material provided an approach to develop highly selective sensing platform for trace bioanalysis.

Intrareticular charge transfer regulated electrochemiluminescence of donor-acceptor covalent organic frameworks.

The control of charge transfer between radical anions and cations is a promising way for decoding the emission mechanism in electrochemiluminescence (ECL) systems. Herein, a type of donor-acceptor (D-A) covalent organic framework (COF) with triphenylamine and triazine units is designed as a highly efficient ECL emitter with tunable intrareticular charge transfer (IRCT). The D-A COF demonstrates 123 folds enhancement in ECL intensity compared with its benzene-based COF with small D-A contrast. Further, the COF's crystallinity- and protonation-modulated ECL behaviors confirm ECL dependence on intrareticular charge transfer between donor and acceptor units, which is rationalized by density functional theory. Significantly, dual-peaked ECL patterns of COFs are achieved through an IRCT mediated competitive oxidation mechanism: the coreactant-mediated oxidation at lower potential and the direct oxidation at higher potential. This work provides a new fundamental and approach to improve the ECL efficiency for designing next-generation ECL devices.

Transformable upconversion metal-organic frameworks for near-infrared light-programmed chemotherapy.

A transformable upconversion MOF comprising a UCNP core and an azobenzene-based MOF shell is designed for NIR light-modulated chemotherapy. The dual Förster resonance energy transfers (FRETs) involved in this delivery system trigger the transformation of the MOF for drug release and prodrug activation, thus significantly inhibiting the tumor growth and metastasis.

Dual Intrareticular Oxidation of Mixed-Ligand Metal-Organic Frameworks for Stepwise Electrochemiluminescence.

This work presents a mixed-ligand metal-organic framework (m-MOF) integrated with two ligands, one as a luminophore and the other as a coreactant, on one metal node for self-enhanced electrochemiluminescence (ECL). Both 9,10-di(p-carboxyphenyl)anthracene (DPA) and 1,4-diazabicyclo[2.2.2]octane (D-H2) ligands can be oxidized, generating the cation radicals DPA+• and D-H2+•, respectively. The latter can be deprotonated to form the neutral radical (D-H•) and then react with DPA+• to produce excited DPA* for ECL emission without exogenous coreactants. As a result of the incorporation into the MOF framework and the intrareticular charge transfer between the two ligands, the ECL intensity of the m-MOF was increased 26.5-fold compared with that of the mixture of DPA and D-H2 in aqueous solution. Moreover, with the process of second oxidation of D-H2, stepwise ECL emission was observed as a result of local excitation in the DPA unit, which was identified through density functional theory calculations. Overall, the implementation of the mixed-ligand approach, which combines the luminophore and coreactant as linkers in reticular materials, enriches the fundamentals and applications of ECL systems.

Parallel Lipid Peroxide Accumulation Strategy Based on Bimetal-Organic Frameworks for Enhanced Ferrotherapy.

Ferroptosis, a nonapoptotic cell-death pathway, is commonly regulated by ether lipid peroxide generation or glutathione consumption. In this work, a parallel lipid peroxide accumulation strategy was designed based on catalytic metal-organic frameworks (MOFs) for enhanced ferrotherapy. The bimetallic MOF was synthesized with iron porphyrin as a linker and cupric ion as a metal node, and erastin, a ferroptosis inducer, was sandwiched between the MOF layers with 4,4'-dipyridyl disulfide as spacers. In a tumor microenvironment, erastin was released from the layered MOFs through glutathione-responsive cleavage. The exfoliated MOFs served as a dual Fenton reaction inducer to generate numerous hydroxyl radicals for the accumulation of lipid peroxide, while erastin-aggravated glutathione depletion down-regulated glutathione peroxidase 4; this then inhibited the consumption of lipid peroxide. Therefore, a parallel lipid peroxide accumulation strategy was established for enhanced ferrotherapy that effectively inhibited tumor growth in live mice, opening up new opportunities to treat apoptosis-insensitive tumors.

Hypoxia-stimulated tumor therapy associated with the inhibition of cancer cell stemness.

Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer stemness. The triblock precursor was designed with a fluorescence chromophore for monitoring hypoxia, a methoxy nitro-unit for biorecognition, and a poly(ethylene glycol)-folate for cancer cell targeting. As the degree of hypoxia increases, the vectors were progressively dissociated as indicated by the enhanced fluorescence intensity in hypoxic cells and compacted three-dimensional spheres. Furthermore, the expression of stem cell markers such as CD133 and SOX2 was significantly inhibited, and the serial passaging of CSCs was notably impaired after treating CSCs with the vectors. The inhibition of cancer cell stemness significantly improved the anticancer efficiency in vivo. Moreover, tumor initiation was reduced and the median survival time of xenograft tumor models was prolonged by regulating cell stemness under hypoxia. Overall, this work provides a promising approach to inhibit tumor resistance and recurrence for efficient tumor therapy.