In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Molecularly imprinted polymers-coated magnetic covalent organic frameworks for efficient solid-phase extraction of sulfonamides in fish.

In this study, covalent organic frameworks (COFs) were grown in situ on magnetic nitrogen-doped graphene foam (MNGF), and the resulting composite of COFs-modified MNGF (MNC) was wrapped by molecularly imprinted polymers (MNC@MIPs) for specifically capturing SAs. A magnetic solid phase extraction (MSPE) method for SAs was established using MNC@MIPs with good magnetic responsiveness. The adsorption performance of MNC@MIPs was superior to that of non-molecularly imprinted polymers (MNC@NIPs), with shorter adsorption/desorption time and higher imprinting factors. A high-efficiency SAs analytical method was developed by fusing HPLC and MNC@MIPs-based MSPE. This approach provides excellent precision, a low detection limit, and wide linearity. By analyzing fish samples, the feasibility of the approach was confirmed, with SAs recoveries and relative standard deviations in spiked samples in the ranges of 77.2-112.7 % and 2.0-7.2 %, respectively. This study demonstrated the potential use of MNC@MIPs-based MSPE for efficient extraction and quantitation of trace hazards in food.

Post-modification of covalent organic framework functionalized aminated carbon nanotubes with active site (Fe) for the sensitive detection of luteolin.

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.

Toward understanding ammonia capture in two amino-functionalized metal-organic frameworks using in-situ infrared spectroscopy and DFT calculation.

Two isostructural, three-dimensional, interpenetrated amino-functionalized Metal-Organic Frameworks (Co-2AIN-MOF and Cd-2AIN-MOF) based on 2-aminoisonicotinic acid (2AIN) were synthesized, structurally characterized and determined. Based on the PXRD analysis, the solvent exchange hardly changed their framework structure, and the samples fully activated by methanol can be achieved and examined by infrared spectroscopy. Due to the presence of the carbonyl group and free amino groups in the pore of the framework, the NH3 uptakes of Co-2AIN-MOF and Cd-2AIN-MOF are 11.70 and 13.81 mmol/g and at 1 bar, respectively. In-situ Infrared spectroscopy and DFT calculations revealed the different adsorption sites and processes between Co-2AIN-MOF and Cd-2AIN-MOF.

Fluorescent hydrogen-bonded organic framework act as a multifunctional platform for Fe3+ and F- sensing, and for information encryption.

Due to their exceptional optical properties and adjustable functional characteristics, hydrogen-bonded organic frameworks (HOFs) demonstrate significant potential in applications such as sensing, information encryption. However, studies on the synthesis of HOFs designed to construct multifunctional platforms are scant. In this work, we report the synthesis of a new fluorescent HOF by assembling melem and isophthalic acid (IPA), designated as HOF-IPA. HOF-IPA exhibited good selectivity and sensitivity towards Fe3+, making it suitable as a fluorescent sensor for Fe3+ detection. The sensor achieved satisfactory recoveries ranging from 97.79 % to106.42 % for Fe3+ sensing, with a low relative standard deviation (RSD) of less than 3.33 %, indicating significant application potential for HOF-IPA. Due to the ability of F- to mask the electrostatic action on the surface of Fe3+ and inhibit the photoelectron transfer (PET) of HOF-IPA, the HOF-IPA - Fe3+ system can be utilized as a fluorescent "off-on" sensor for F- detection. Additionally, owing to the colorless, transparent property of HOF-IPA in aqueous solution under sunlight and its blue fluorescence property under UV light (color) or microplate reader (fluorescence intensity), HOF-IPA based ink can be used for various types of information encryption, and all yielding favorable outcomes.

2D copper-iron bimetallic metal-organic frameworks for reduction of nitrate with boosted efficiency and ammonia selectivity.

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.

MOFs with the Stability for Practical Gas Adsorption Applications Require New Design Rules.

Metal-organic frameworks (MOFs) have been widely studied for their ability to capture and store greenhouse gases. However, most computational discovery efforts study hypothetical MOFs without consideration of their stability, limiting the practical application of novel materials. We overcome this limitation by screening hypothetical ultrastable MOFs that have predicted high thermal and activation stability, as judged by machine learning (ML) models trained on experimental measures of stability. We enhance this set by computing the bulk modulus as a measure of mechanical stability and filter 1102 mechanically robust hypothetical MOFs from a database of ultrastable MOFs (USMOF DB). Grand Canonical Monte Carlo simulations are then employed to predict the gas adsorption properties of these hypothetical MOFs, alongside a database of experimental MOFs. We identify privileged building blocks that lead MOFs in USMOF DB to show exceptional working capacities compared to the experimental MOFs. We interpret these differences by training ML models on CO2 and CH4 adsorption in these databases, showing how poor model transferability between data sets indicates that novel design rules can be derived from USMOF DB that would not have been gathered through assessment of structurally characterized MOFs. We identify geometric features and node chemistry that will enable the rational design of MOFs with enhanced gas adsorption properties in synthetically realizable MOFs.

A Highly Conjugated Nickel(II)-Acetylide Framework for Efficient Photocatalytic Carbon Dioxide Reduction.

The incorporation of transition-metal single atoms as molecular functional entities into the skeleton of graphdiyne (GDY) to construct novel two-dimensional (2D) metal-acetylide frameworks, known as metalated graphynes (MGYs), is a promising strategy for developing efficient catalysts, which can combine the tunable charge transfer of GDY frameworks, the catalytic activity of metal and the precise distribution of single metallic centers. Herein, four highly conjugated MGY photocatalysts based on NiII, PdII, PtII, and HgII were synthesized for the first time using the 'bottom-up' strategy through the use of M-C bonds (-C≡C-M-C≡C-). Remarkably, the NiII-based graphyne (TEPY-Ni-GY) exhibited the highest CO generation rate of 18.3 mmol g-1 h-1 and a selectivity of 98.8%. This superior performance is attributed to the synergistic effects of pyrenyl and -C≡C-Ni(PBu3)2-C≡C- moieties. The pyrenyl block functions as an intramolecular π-conjugation channel, facilitating kinetically favorable electron transfer, while the -C≡C-Ni(PBu3)2-C≡C- moiety serves as the catalytic site that enhances CO2 adsorption and activation, thereby suppressing competitive hydrogen evolution. This study provides a new perspective on MGY-based photocatalysts for developing highly active and low-cost catalysts for CO2 reduction.

A Versatile Metal-Organic-Framework Pillared Interlayer Design for High-Capacity and Long-Life Lithium-Sulfur Batteries.

Developing high-performance lithium-sulfur batteries is a promising way to attain higher energy density at lower cost beyond the state-of-the-art lithium-ion battery technology. However, the major issues blocking their practical application are the sluggish kinetics and parasitic shuttling reactions for sulfur and polysulfides. Here, pillaring multilayer graphene with the metal-organic framework (MOF) demonstrates the substantial impact of a versatile interlayer design in tackling those issues. Unlike regular composite separators reported so far, the participation of tri-metallic Ni-Co-Mn MOF (NCM-MOF) as pillars supports the construction of an ion-channel interconnected interlayer structure, unexpectedly balancing the interfacial concentration polarization, spatially confining the soluble polysulfides and vastly affording lithiophilic sites for highly efficient polysulfide sieving/conversion. As a demonstration, we show that the MOF-pillared interlayer structure enables outstanding capacity (1634 mAh g-1 at 0.1C) and longevity (average capacity decay of 0.034% per cycle in 2000 cycles) of lithium-sulfur batteries. Besides, the multilayer separator can be readily integrated into the high-nickel cathode (LiNi0.91Mn0.03Co0.06O2)-based lithium-ion batteries, which efficiently suppresses the undesired phase evolution upon cycling. These findings suggest the potential of "gap-filling" materials in fabricating multi-functional separators, bring forward the pillared interlayer structure for energy-storage applications.

Machine Learning Predictions of Methane Storage in MOFs: Diverse Materials, Multiple Operating Conditions, and Reverse Models.

A machine learning (ML) model is developed for predicting useable methane (CH4) capacities in metal-organic frameworks (MOFs). The model applies to a wide variety of MOFs, including those with and without open metal sites, and predicts capacities for multiple pressure swing conditions. Despite its wider applicability, the model requires only 5 measurable structural features as input, yet achieves accuracies that surpass less-general models. Application of the model to a database of more than a million hypothetical MOFs identified several hundred whose capacities surpass that of the benchmark MOF, UMCM-152. Guided by the computational predictions, one of the promising candidates, UMCM-153, was synthesized and demonstrated to achieve superior volumetric capacity for CH4. Feature importance analyses reveal that pore volume and gravimetric surface area are the most important features for predicting CH4 capacity in MOFs. Finally, a reverse ML model is demonstrated. This model predicts the set of elementary MOF structural properties needed to achieve a desired CH4 capacity for a prescribed operating condition.

Recent progress of chiral metal-organic frameworks in enantioselective separation and detection.

Chiral compounds are abundantly distributed in both the natural world and biological systems. It is crucial to identify and detect chiral compounds in living systems or to separate and determine them in the natural environment. Many researchers have developed a range of chiral materials with different functionalizations to separate and detect chiral substances. Chiral metal-organic frameworks (CMOFs) have the potential to be used in enantioselective separation and detection due to their large surface areas, regulated framework topologies, particular substrate interactions, and accessible chiral sites. CMOFs contribute significantly to the development of enantiomer separation and detection in medicine, agriculture, food, environment, and other fields. This review focuses on four synthesis methods of CMOFs and their applications in chiral separation and chiral sensing in the past five years, mainly including chromatographic separation, membrane separation, optical sensing, electrochemical sensing, and other sensing methods. Finally, the challenges and potential growth direction of CMOFs in enantiomer separation and detection are discussed and prospected.

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar-Driven Photothermal Effect.

Developing new enzyme-immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition-elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post-modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar-driven photothermal-promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy-efficient approach to facilitate the scale application of enzyme-immobilized biocatalysts.

Hydrogen-Bonded Organic Frameworks for Antibiotic Fluorescent Sensing Artificial Intelligence-Enhanced Anticounterfeiting.

The paramount importance of anticounterfeiting measures in safeguarding consumers from counterfeit products lies in their ability to ensure product safety and reliability. Advanced luminescent anticounterfeiting materials, particularly those responsive to multiple stimuli, afford a dynamic and multilayered security assurance. This study presents the synthesis of a novel material, Eu/Tb@GC-3, via postsynthetic modification, which exhibits notable photoluminescent properties with emission at 544 and 614 nm. The material demonstrates high selectivity and sensitivity in detecting Nitrofural and Enrofloxacin, with limits of detection at 0.0122 and 0.0280 µM, respectively. Furthermore, multistimulus responsive luminescent fibers and inks were developed, facilitating intelligent anticounterfeiting labels. The integration of these labels with back-propagation neural networks (BPNNs) significantly enhances pattern recognition and authentication capabilities, providing an efficacious strategy to combat counterfeit products and ensure consumer safety.

Ecological and health implications of heavy metal bioaccumulation in Thai Fauna: A systematic review.

Heavy metals pose significant threats to ecosystems and human health due to their persistence and bioaccumulation. In Thailand, rapid industrialization, extensive agriculture, and urban development have exacerbated heavy metal pollution in both aquatic and terrestrial ecosystems. This systematic review, conducted according to PRISMA guidelines, evaluates study designs and methodologies to assess heavy metal bioaccumulation in Thai fauna, with a focus on ecological and health impacts. The review reveals that fish, particularly from families like Cyprinidae and Cichlidae, account for 42.11 % of studies, with species such as swamp eel, Henicorhynchus siamensis, Arius maculatus, Osteogeneiosus militaris, Puntioplites proctozystron, and Channa striata showing significant bioaccumulation. Molluscs (31.58 %), including Tegillarca granosa and Filopaludina martensi, serve as critical bioindicators of aquatic pollution due to their filter-feeding habits. Amphibians and crustaceans, like Fejervarya limnocharis and Fenneropenaeus merguiensis, also demonstrate vulnerability to heavy metal contamination. Key contamination hotspots include urban waterways in Bangkok, industrial discharges in Songkhla Lake, and mining sites in Loei Province, highlighting widespread environmental and health impacts. Despite extensive research, gaps remain, particularly concerning benthic scavengers and detritivores, which are vital for ecosystem functions. The review underscores the need for targeted monitoring and mitigation, including stricter regulations on industrial discharges, improved waste treatment, and better management of agricultural runoff. While metals like cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn) are well-studied, further research on less-examined metals and species-specific bioaccumulation patterns is crucial to enhancing environmental management, supporting biodiversity conservation, and improving ecosystem resilience in Thailand.

Modified Ce/Zr-MOF Nanoparticles Loaded with Curcumin for Alzheimer's Disease via Multifunctional Modulation.

Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy. Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aß1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level. Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-ß deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation. Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.

Unveiling the Microscopic Origin of Ultrahigh Initial Coulombic Efficiency of High-Entropy Metal-Organic Frameworks for Sodium Storage.

The initial irreversible capacity loss during the first charging process largely reduces the affordable energy and power density of sodium storage devices, and developing advanced materials is the efficient way to solve this problem, which is fraught with challenges. Herein, inspired by theoretical calculations and the high-entropy concept, a series of fewer layers of high-entropy metal-organic frameworks (FLHE-MOFs) are successfully fabricated, delivering an ultrahigh initial Coulombic efficiency (ICE) of 86.1% and excellent cycling performance, which is far more than that of the other electrode materials (generally <70%). Greatly, the storage behavior of high-, medium-, and low-entropy MOFs is clarified by theoretical calculations and in-/ex-situ characterization, revealing that Co and Fe species can provide substantial sodium storage sites and largely enhance the charge transfer rate, whereas high-entropy effect can enable structural reversibility. Sodium ion capacitors constructed with FLHE-MOFs as the anode can provide an ultrahigh energy density of 121.8 W h kg-1 (200 W kg-1) and an extremely long-term cycle lifespan. This work not only breaks the limitation of MOF materials with poor performance for sodium storage but also provides an effective strategy for the fabrication and application of high-performance MOF-based anode materials with high ICE, in which this idea may also be applied in other fields.

Ag Nanoparticles-Confined Doped within Triazine-Based Covalent Organic Frameworks for Syngas Production from Electrocatalytic Reduction of CO2.

Electrocatalytic CO2 reduction reaction (CO2RR) emerges as a promising avenue to mitigate carbon emissions, enabling the capture and conversion of CO2 into high-value products such as syngas with CO/H2. One of the crucial aspects lies in the tailored development of durable and efficient electrocatalysts for the CO2RR. Covalent organic frameworks (COFs) possess unique characteristics that render them attractive candidates for catalytic applications. However, the relationship between structure and performance still requires further exploration; especially, most COFs with such properties are limited to COFs containing specific groups such as phthalocyanine or porphyrin groups. Here, we custom-synthesize two azine-linked nitrogen-rich COFs constructed from triazine building blocks, which are doped with ultrafine and highly dispersed Ag nanoparticles (Ag@TFPT-HZ and Ag@TPT-HZ). Thus-obtained COFs can serve as electrocatalysts for the CO2RR, and a comprehensive investigation has been conducted to uncover the intricate structure-performance relationship within these materials. Notably, Ag@TFPT-HZ exhibits superior CO selectivity in the electrocatalytic CO2RR, achieving a FECO of 81% and a partial current density of 7.65 mA·cm-2 at the potential of -1.0 V (vs reversible hydrogen electrode (RHE)). In addition, Ag@TPT-HZ as an electrocatalyst can continuously produce syngas with a CO/H2 molar ratio of 1:1, an ideal condition for methanol synthesis. The observed distinct performance between these two COFs is attributed to the presence of O atoms in TFPT-HZ. These O atoms facilitate a higher loading capacity of Ag nanoparticles (11 wt %) and generate a greater number of active sites, thereby enhancing electrochemical activity and promoting faster reaction kinetics. Therefore, two tailor-made two-dimensional (2D) nitrogen-rich COFs with various active sites as electrocatalysts can exhibit different outstanding electrocatalytic performances for CO2RR and possess high cycling stability (>50 h). This work offers valuable insights into the design and synthesis of electrocatalysts, particularly in elucidating the intricate relationship between their structure and performance.

Metal-organic frameworks (MOFs) and their derivatives as emerging biomaterials for the treatment of osteoarthritis.

As a novel class of smart biomaterials with promising potentials, metal-organic frameworks (MOFs) are widely utilized in the field of biomedicine. Current researches indicate that the therapeutic strategies for osteoarthritis (OA) are highly limited to achieving symptom improvement and reducing both pain and inflammation. Together, the introduction of MOFs into the treatment of OA holds the potential to offer significant benefits. This is because MOFs not only have intrinsic biological activities, but also act as carriers to facilitate controlled drug delivery and prolong the duration in the management of OA. This paper presents a review of the recent studies that have explored the potential usage of MOFs as drugs or carriers in the treatment of OA, which also examines the progress of MOFs in tissue engineering for the treatment of OA. These studies are anticipated to not only enhance the comprehension of MOFs but also provide strong evidence in favor of their utilization in the treatment of OA.

Freestanding Hydrogen-Bonded Organic Framework Membrane for Efficient Wound Healing.

Hydrogen-bonded organic frameworks (HOFs) are emerging as multifunctional materials with exceptional biocompatibility, abundant active sites, and tunable porosity, which are highly beneficial for advanced wound care. However, a significant challenge involves transforming pristine HOFs powders into lightweight, ultrathin, freestanding membranes compatible with soft biological systems. Herein, the study successfully develops shape-adaptive HOF-based matrix membranes (HMMs) using a polymer-assisted liquid-air interface technique. The HMMs conform seamlessly to tissues of different sizes and shapes, effectively stopping bleeding, and provide high water-vapor permeability. Notably, both in vitro and in vivo studies with mice wound models demonstrated that these tissue-conformable HMMs significantly accelerate wound healing by modulating the inflammatory environment of the injured tissue and promoting rapid re-epithelialization. Furthermore, RNA-seq analysis and mechanistic studies revealed that HMMs effectively reduce inflammation and facilitate the tissue transition from the proliferative stage to the remodeling stage of skin development. This work not only opens up new avenues for advanced wound care materials but also establishes a foundation for hybridizing HOFs with polymers for a wide range of potential applications.

Phenanthridine-based Covalent Organic Frameworks for Boosting Overall Solar H2O2 Production.

Solar-driven H2O2 production via the oxygen reduction reaction (ORR) and water oxidation reaction (WOR) dual channels is green and sustainable, but severely restricted by the sluggish reaction kinetics. Constructing intriguing photocatalysts with effective active centers is a shortcut to breaking the kinetic bottleneck with great significance. Herein, we synthesize two novel neutral phenanthridine-based covalent organic frameworks (PD-COF1 and PD-COF2) for photosynthesizing H2O2. Compared to the no phenanthridine counterpart (AN-COF), the H2O2 photosynthetic activities of PD-COF1 and PD-COF2 are markedly boosted. In air and pure water without sacrificial agents, under Xe lamp and natural sunlight, the H2O2 photogeneration rate of PD-COF2 is 6103 and 3646 µmol g-1 h-1, respectively. Further experimental and theoretical inspections demonstrate that introducing phenanthridine units into COFs smoothly modulates the charge carrier dynamics and thermodynamically favors the generation of crucial OOH* and OH* intermediates in the ORR and WOR paths, respectively. Additionally, this is the first time the neutral phenanthridine moiety serves as the photooxidation unit for 2e- WOR towards H2O2 photoproduction. The current work sheds light on exploring novel catalytic centers for high-performance H2O2 evolution.