Reactive Oxygen Species Generation Efficiency Research Articles

Highly efficient photo-driven generation and elimination of reactive oxygen species in biological environment by gold nanoclusters

Reactive oxygen species (ROS) play an essential role in cell signalling, pathogen defence, and maintaining cellular homeostasis. The photocatalysts are highly desired in the photo-driven in-situ ROS generation and elimination in biological environment. Here, we present the highly efficient photo-driven generation and elimination of ROS in biological environment by glutathione (GSH)-protected gold nanoclusters (AuNCs). In extracellular environment, AuNCs can generate hydrogen peroxide (H2O2) through a two-electron oxygen reduction reaction (ORR) without any additional sacrifices. On the other hand, in intracellular environment, AuNCs are capable of eliminating the ROS in cells under visible light. For the photocatalyst of GSH protected AuNCs, the photogenerated electrons are in response to reduction reactions, and meanwhile photogenerated holes can oxidize the GSH ligands, protecting other biomolecules from oxidation reactions. This work opens a new gate for the concentration manipulation of ROS in the biological environment as well as the real-time regulation of ROS in organisms.

Rational Design of AIE Photosensitizers with Full‐Visible Color Emission and Efficient ROS Generation

AbstractOrganic photosensitizers (PSs) with aggregation‐induced emission (AIE) characteristics have shown several advantages in photodynamic therapy (PDT). However, how to design PSs with the required optical and biological properties is a formidable challenge. In this work, a series of AIE active pyridine‐ and pyridinium‐functionalized carbazole with different substituents are designed and synthesized. Compared to other analogs, BK‐Pys‐BP containing benzophenone moiety on the pyridinium unit produces reactive oxygen species (ROS) efficiently in the presence of light due to its large spin‐orbit coupling constant to promote efficient intersystem crossing. Based on its structure, three molecules with enhanced donor–acceptor strength and conjugation are further investigated to realize emission covering the whole visible region. The cationic nature and excellent ROS generation ability of benzophenone‐containing AIE photosensitizers allows for specific imaging of mitochondria, killing cancer cells, and as a singlet oxygen donor to catalyze the formation of endoperoxides. Thus, the present work presents an effective strategy for creating AIE photosensitizers with efficient ROS generation for wide biological applications.

Harnessing Efficient ROS Generation in Carbon Dots Derived from Methyl Red for Antimicrobial Photodynamic Therapy.

The emergence of drug-resistant pathogenic microorganisms has become a public health concern, with demand for strategies to suppress their proliferation in healthcare facilities. The present study investigates the physicochemical and antimicrobial properties of carbon dots (CD-MR) derived from the methyl red azo dye. The morphological and structural analyses reveal that such carbon dots present a significant fraction of graphitic nitrogen in their structures, providing a wide emission range. Based on their low cytotoxicity against mammalian cells and tunable photoluminescence, these carbon dots are applied to bioimaging in vitro living cells. The possibility of using CD-MR to generate reactive oxygen species (ROS) is also analyzed, and a high singlet oxygen quantum efficiency is verified. Moreover, the antimicrobial activity of CD-MR is analyzed against pathogenic microorganisms Staphylococcus aureus, Candida albicans, and Cryptococcus neoformans. Kirby-Bauer susceptibility tests show that carbon dots synthesized from methyl red possess antimicrobial activity upon photoexcitation at 532 nm. The growth inhibition of C. neoformans from CD-MR photosensitization is investigated. Our results show that N-doped carbon dots synthesized from methyl red efficiently generate ROS and possess a strong antimicrobial activity against healthcare-relevant pathogens.

Linker Engineering for Reactive Oxygen Species Generation Efficiency in Ultra-Stable Nickel-Based Metal-Organic Frameworks.

Interfacial charge transfer on the surface of heterogeneous photocatalysts dictates the efficiency of reactive oxygen species (ROS) generation and therefore the efficiency of aerobic oxidation reactions. Reticular chemistry in metal-organic frameworks (MOFs) allows for the rational design of donor-acceptor pairs to optimize interfacial charge-transfer kinetics. Herein, we report a series of isostructural fcu-topology Ni8-MOFs (termed JNU-212, JNU-213, JNU-214, and JNU-215) with linearly bridged bipyrazoles as organic linkers. These crystalline Ni8-MOFs can maintain their structural integrity in 7 M NaOH at 100 °C for 24 h. Experimental studies reveal that linker engineering by tuning the electron-accepting capacity of the pyrazole-bridging units renders these Ni8-MOFs with significantly improved charge separation and transfer efficiency under visible-light irradiation. Among them, the one containing a benzoselenadiazole unit (JNU-214) exhibits the best photocatalytic performance in the aerobic oxidation of benzylamines with a conversion rate of 99% in 24 h. Recycling experiments were carried out to confirm the stability and reusability of JNU-214 as a robust heterogeneous catalyst. Significantly, the systematic modulation of the electron-accepting capacity of the bridging units in donor-acceptor-donor MOFs provides a new pathway to develop viable noble-metal-free heterogeneous photocatalysts for aerobic oxidation reactions.

Meticulously Designed Carbon Dots as Photo-Triggered RNA-Destroyer for Evoking Pyroptosis.

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high 1O2 quantum yield (φΔ = 38.85%) and superior RNA selectivity. Moreover, the φΔ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm-2, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.

Bisbenzothieno[b]-fused BODIPYs as efficient near-infrared heavy-atom-free photosensitizers

Fusion thiophene to BODIPY endows the chromophore with more fundamental and special functions. Herein, novel symmetric bisbenzothieno[b]-fused BODIPYs (BTBs) were synthesized and developed. These newly prepared BTB dyes possessed absorption maxima in the range of 643–665 nm, and many outstanding properties including large molar extinction coefficients, and high singlet oxygen generation. Theoretical calculations affirmed that the smaller singlet-triplet energy gap and larger spin−orbit coupling result in efficient intersystem crossing, thus increasing the singlet oxygen generation yield. Notably, Me2NPh-substituted BTB displayed good reactive oxygen species generation efficiency up to 0.41, and a remarkable photo-cytotoxicity (IC50 = 83.5 nM) in HeLa cells, which shows potential in low-dose photodynamic therapy.

Vacancy Augmented Piezo-Sonosensitizer for Cancer Therapy.

Sonodynamic therapy (SDT) has been widely reported as a noninvasive and high-penetration therapy for cancer; however, the design of an efficient sonosensitizer remains an urgent need. To address this issue, molybdenum disulfide nanoflowers (MoS2 NF) as piezo-sonosensitizers and introduced sulfur vacancies on the MoS2 NF (Sv-MoS2 NF) to improve their piezoelectric property for cancer therapy are designed. Under ultrasonic mechanical stress, the Sv-MoS2 NF resulted in piezoelectric polarization and band tilting, which enhanced the charge carrier separation and migration. This resulted in an improved catalytic reaction for reactive oxygen species (ROS) production, ultimately enhancing the SDT performance. Thanks to the high efficiency of ROS generation, the Sv-MoS2 NF have demonstrated a good anticancer effect in vitro and in vivo. Following a systematic evaluation, Sv-MoS2 NF also demonstrated good biocompatibility. This novel piezo-sonosensitizer and vacancy engineering strategy provides a promising new approach for achieving efficient SDT.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)-ATCUN Complexes.

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.

ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 μg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.

Aggregation-induced emission near-infrared photosensitizer with time-responsive dual-organelles targeting for accelerating cancer cells apoptosis and metastasis inhibition

Photodynamic therapy (PDT) combined with critical organelle targeting can maximize ablation of malignant tumors, which is a desirable route against cancer. However, the short excitation/emission wavelengths of conventional photosensitizers (PSs), the inefficient production of reactive oxygen species (ROS) and the inevitable aggregation-induced quenching phenomenon have restricted their development. Herein, we developed and synthesized a set of photoactivated fluorescent probes named MoTQu and MeTQu with aggregation-induced emission properties. The both of fluorescent probes have merits of bright near-infrared fluorescence emission, large stokes shift and enhanced intramolecular charge transfer attributed to the synergistic interaction of strong donor and acceptor of molecular. In addition, the optimal PS named MoTQu not only possesses superior anti-photobleaching, biocompatibility and extremely high-level ROS generation efficiency, on the other hand, can time-responsive target mitochondria and lysosomes in living cells to cause lysosomal dysfunction by generating large amount of ROS in situ under photoexcitation, subsequently targeting mitochondria through the positive electrical properties of the quinoline fraction, further inducing and promoting cancer cell damage and irreversible apoptosis. Consequently, we are convinced that MoTQu can be a powerful tool to foster the development of image-guided PDT.

Constructing efficient and photostable photosensitizer with aggregation-induced emission by introducing highly electronegative nitrogen atom for photodynamic therapy

Photodynamic therapy (PDT) has drawn considerable attention owning to many unique advantages, such as precise controllability, noninvasiveness, high efficiency and spatiotemporal selectivity. However, most of the currently utilized photosensitizers (PSs) have drawbacks of weak light absorption for excitation and low reactive oxygen species (ROS) generation ability. In this contribution, through introducing highly electronegative nitrogen atom, two photostable photosensitizers are designed to display high absorption coefficient and efficient ROS generation ability. The yield BTPTT-CNTPE nanoparticles show good performance of excellent photostability, high ROS generation efficiency, negligible dark toxicity and high absorption coefficient. Subsequent PDT experiments both in vitro and in vivo prove that BTPTT-CNTPE nanoparticles are promising candidates for PDT anticancer therapy.

2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy.

Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO4 artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy-rich BiVO4 nanosheets (abbreviated Vv -r BiVO4 NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the Vv -r BiVO4 NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O2 /O2 •- and H2 O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, Vv -r BiVO4 NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.

An Alkaline Phosphatase-Responsive Aggregation-Induced Emission Photosensitizer for Selective Imaging and Photodynamic Therapy of Cancer Cells.

Fluorescence-guided photodynamic therapy (PDT) has been considered as an emerging strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation. Some efficient PSs have been reported in recent years, but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP) on a PS with the features of aggregation-induced emission (AIE) for cancer cell imaging and therapy. In cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the hydrophobic probe residue is aggregated in aqueous media and gives a "turn on" fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a strategy of applying ALP-responsive AIE PS for specific imaging cancer cells and succeeding with specific PDT upon the cancer biomarker stimulated responsive reactions.

Construction and elucidation of zerovalent iron@terephthalic acid/iron oxide catalyst to activate peroxymonosulfate for accelerating and long-lasting NOx removal

Recently peroxymonosulfate (PMS)-based advanced oxidation techniques (AOTs) have been widely used nowadays for pollutant removal. However, Fenton/Fenton-like reactions using Fe-based catalysts are highly promising for the NOx treatment due to their improved catalytic efficiency, low cost, and offering effectual reactive oxygen species (ROS). However, the long-term reusability without generating (Fe) sludge and its inactivation due to the non-spontaneous conversion of Fe(II)/Fe(III) are problematic. Hence, a variety of catalysts had been employed to activate Fe(II) and for efficient ROS generation. In this work, we designed a single metal-based stable and heterogeneous Fenton-like technology (SMHFT) with Fe3O4 (base material) functionalized using 2-amino terephthalic acid (ATA) to increase stability and surface area. The Fe3O4@ATA composite was finally decorated using solid zero-valent-iron (Fe0) (i.e., MTAFe0), where terminal Fe0 offers an active surface for ultrafast PMS activation and efficient ROS generation. The ROS containing SO4-•, HO•, and 1O2 entities are entirely used for NO oxidation with better mass transfer without using an electron (e-) mediator and restored Fe-efficiency. The electron paramagnetic resonance (EPR) and various scavengers verified the ROS participating in NO oxidation significantly, as well as in-situ regeneration of the catalyst. The synthesized MTAFe0 showed ∼ 94 % efficiency, and the density functional theory (DFT) elucidated PMS adsorption and its ultrafast activation by ROS generation. Finally, the reusability of MTAFe0 was investigated, and it showed over 90% efficiency after 10-continuous cycles. Hence, the developed SMHFT system has great potential for fast NO removal with long-term utilization, which is promising and could be implemented sustainability for air pollution treatment.

Missing‐Linker‐Confined Single‐Atomic Pt Nanozymes for Enzymatic Theranostics of Tumor

AbstractConventional nanozymes often possess low active site density. Pursuing effective strategies for constructing highly active single‐atomic nanosystems with maximum atom utilization efficiency is exceptionally attractive. Herein, we develop a facile “missing‐linker‐confined coordination” strategy to fabricate two self‐assembled nanozymes, i.e., conventional nanozyme (NE) and single‐atomic nanozyme (SAE), which respectively consist of Pt nanoparticles and single Pt atoms as active catalytic sites anchored in metal–organic frameworks (MOFs) with encapsulated photosensitizers for catalase‐mimicking enhanced photodynamic therapy. Compared to a Pt nanoparticle‐based conventional nanozyme, a Pt single‐atomic nanozyme shows enhanced catalase‐mimicking activity in generating oxygen for overcoming tumor hypoxia, thus exhibiting a more efficient reactive oxygen species generation and high tumor inhibition rate.

Missing-Linker-Confined Single-Atomic Pt Nanozymes for Enzymatic Theranostics of Tumor.

Conventional nanozymes often possess low active site density. Pursuing effective strategies for constructing highly active single-atomic nanosystems with maximum atom utilization efficiency is exceptionally attractive. Herein, we develop a facile "missing-linker-confined coordination" strategy to fabricate two self-assembled nanozymes, i.e., conventional nanozyme (NE) and single-atomic nanozyme (SAE), which respectively consist of Pt nanoparticles and single Pt atoms as active catalytic sites anchored in metal-organic frameworks with encapsulated photosensitizers for catalase-mimicking enhanced photodynamic therapy. Compared to Pt nanoparticle-based conventional nanozyme, Pt single-atomic nanozyme shows enhanced catalase-mimicking activity in generating oxygen for overcoming tumor hypoxia, thus presenting more efficient reactive oxygen species generation and high tumor inhibition rate.

Defect-Modified nano-BaTiO3 as a Sonosensitizer for Rapid and High-Efficiency Sonodynamic Sterilization.

Multidrug-resistant bacteria caused by the unlimited overuse of antibiotics pose a great challenge to global health. An antibacterial method based on reactive oxygen species (ROS) is one of the effective strategies without inducing bacterial resistance. Owing to the ability of generating ROS, piezocatalytic material-mediated sonodynamic therapy (SDT) has drawn much attention. However, its major challenge is the low ROS generation efficiency in the piezocatalytic process due to the poor charge carrier concentration of piezoelectric materials. Vacancy engineering can regulate the charge density and largely promote ROS generation under ultrasound (US) irradiation. Herein, a US-responsive self-doped barium titanate with controlled oxygen vacancy (Vo) concentrations was successfully synthesized through a facile thermal reduction treatment at different temperatures (i.e., 350, 400, and 450 °C), and the corresponding samples were named as BTO-350, BTO-400, and BTO-450, respectively. Then, the effect of Vo concentrations on ROS generation efficiency during the piezocatalytic process was systematically studied. And BTO-400 was found to possess the highest piezocatalytic activity and excellent sonodynamic antibacterial performance against Escherichia coli and Staphylococcus aureus. Furthermore, its antibacterial mechanism was confirmed that the ROS generated under US could damage bacterial cell membrane and cause considerable leakage of cytoplasmic components and irreversible death of bacteria. Notably, the in vivo results illustrated that the BTO-400 could serve as an effective antibacterial agent and accelerate skin healing via SDT therapy. In all, the Vo defect-modified nano-BaTiO3 has a noticeable potential to induce a rapid and efficient sterilization as well as skin tissue repair by SDT.

Hyaluronic acid-covered piezoelectric nanocomposites as tumor microenvironment modulators for piezoelectric catalytic therapy of melanoma

Increasing the formation of reactive oxygen species (ROS) and reducing the elimination of ROS are the two main objectives in the development of novel inorganic sonosensitizers for use in sonodynamic therapy (SDT). Therefore, BTO–Pd–MnO2–HA nanocomplexes with targeted tumor cells and degradable oxygen-producing shells were designed as piezoelectric sonosensitizers for enhancing SDT. The deposition of palladium particles (Pd NPs) leads to the formation of Schottky junctions, promoting the separation of electron–hole pairs and thereby increasing the efficiency of toxic ROS generation in SDT. The tumor microenvironment (TME) triggers the degradation of MnO2, and the released Mn2+ ions catalyze the generation of hydroxyl radicals (•OH) from H2O2 through a Fenton-like reaction. BTO–Pd–MnO2–HA can continuously consume glutathione (GSH) and generate O2, thereby improving the efficiency of SDT and chemodynamic therapy (CDT). A multistep enhanced SDT process mediated by the piezoelectric sonosensitizers BTO–Pd–MnO2–HA was designed, targeted by hyaluronic acid (HA), activated by decomposition in TME, and amplified by deposition of Pd. This procedure not only presents a new alternative for the improvement of sonosensitizers but also widens the application of piezoelectric nanomaterials in biomedicine.

Recent Advances of Photoactive Near-Infrared Carbon Dots in Cancer Photodynamic Therapy

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs.

Revealing the synergistic mechanism of generation, release, migration and utilization of reactive oxygen species through tailoring the d-band in metal organic frameworks for water purification

Reactive oxygen species (ROS) play important roles in environmental, chemical and biological fields, but the controlled release and migration of ROS remain a major challenge. Here, a highly efficient catalyst (Cu-MIL-101(Fe)) by modifying the electronic structure was designed. The orbital hybridization achieves a deep optimization of the d-band (d band center shifted from −1.01 eV to −1.32 eV), which reduces bonding and antibonding orbitals energy levels, thus promoting release of SO4·-. More importantly, the interfacial micro-electric field (IMEF) formed by the intramolecular charge offset mediates the directional migration of SO4·- from Fe sites to Cu sites. These properties endow the catalyst with high-efficiency SO4·- generation, rapid release, directional migration and utilization, with a 4.3-fold increase in effective oxidant utilization over Fe2+ (from 17.12% to 73.54%). This study highlights a catalytic strategy for efficient ROS generation, release, migration and utilization for a wide range of potential applications including environmental remediation.