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Unveiling Low Temperature Assembly of Dense Fe‐N4 Active Sites via Hydrogenation in Advanced Oxygen Reduction Catalysts

2024-04-04T13:08:01+00:00April 4th, 2024|Categories: Publications|Tags: , |

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N4 site without the Fe nanoparticle (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dechlorination processes in the synthesis, efficiently favouring Fe-N4 site formation without Fe nanoparticle clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behavior of the Fe-N-C material. The FeNC-H2-360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt%) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm-2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M = Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings.

Published in: "Angewandte Chemie International Edition".

Droplet‐Based Microfluidics Reveals Insights into Cross‐Coupling Mechanisms over Single‐Atom Heterogeneous Catalysts

2024-04-03T13:07:59+00:00April 3rd, 2024|Categories: Publications|

Developing recyclable heterogeneous catalysts for organic synthesis requires a deep understanding of active site architectures during surface-catalyzed reactions. Our approach, combining in-situ X-ray absorption spectroscopy and droplet-based microfluidics, investigates Suzuki–Miyaura coupling over palladium single-atoms on carbon nitride. The results highlight the need for distinct design criteria compared to traditional homogeneously catalyzed processes. Abstract Single-atom heterogeneous catalysts (SACs) hold promise as sustainable alternatives to metal complexes in organic transformations. However, their working structure and dynamics remain poorly understood, hindering advances in their design. Exploiting the unique features of droplet-based microfluidics, we present the first in-situ assessment of a palladium SAC based on exfoliated carbon nitride in Suzuki–Miyaura cross-coupling using X-ray absorption spectroscopy. Our results confirm a surface-catalyzed mechanism, revealing the distinct electronic structure of active Pd centers compared to homogeneous systems, and providing insights into the stabilizing role of ligands and bases. This study establishes a valuable framework for advancing mechanistic understanding of organic syntheses catalyzed by SACs.

Published in: "Angewandte Chemie International Edition".

Ionic Covalent Organic Frameworks in Adsorption and Catalysis

2024-04-03T13:07:57+00:00April 3rd, 2024|Categories: Publications|Tags: |

The ion extraction and electro/photo catalysis are promising methods to address environmental and energy issues. Covalent organic frameworks (COFs) are a class of promising template to construct absorbents and catalysts because of their stable frameworks, high surface areas, controllable pore environments, and well-defined catalytic sites. Among them, ionic COFs as unique class of crystalline porous materials, with charges in the frameworks or along the pore walls, have shown different properties and resulting performance in these applications with those from charge-neutral COFs. In this review, current research progress based on the ionic COFs for ion extraction and energy conversion, including cationic/anionic materials and electro/photo catalysis is reviewed in terms of the synthesis strategy, modification methods, mechanisms of adsorption and catalysis, as well as applications. Finally, we demonstrated the current challenges and future development of ionic COFs in design strategies and applications.

Published in: "Angewandte Chemie International Edition".

Electronic Metal‐support Interactions Boost *OOH Intermediate Generation in Cu/In2Se3 for Electrochemical H2O2 Production

2024-04-03T13:07:56+00:00April 3rd, 2024|Categories: Publications|Tags: , , |

Two-electron oxygen reduction reaction (2e- ORR) is a promising method for the synthesis of hydrogen peroxide (H2O2). However, high energy barriers for the generation of key *OOH intermediates hinder the process of 2e- ORR. Herein, we prepared a copper-supported indium selenide catalyst (Cu/In2Se3) to enhance the selectivity and yield of 2e- ORR by employing an electronic metal–support interactions (EMSIs) strategy. EMSIs-induced charge rearrangement between metallic Cu and In2Se3 is conducive to *OOH intermediate generation, promoting H2O2 production. Theoretical investigations reveal that the inclusion of Cu significantly lowers the energy barrier of the 2e- ORR intermediate and impedes the 4e- ORR pathway, thus favoring the formation of H2O2. The concentration of H2O2 produced by Cu/In2Se3 is ~2 times than In2Se3, and Cu/In2Se3 shows promising applications in antibiotic degradation. This research presents a valuable approach for the future utilization of EMSIs in 2e- ORR.

Published in: "Angewandte Chemie International Edition".

Supramolecular Chemistry of Sumanene

2024-04-02T13:08:18+00:00April 2nd, 2024|Categories: Publications|

This Minireview summarizes recent advances in the growing field of the applied supramolecular chemistry of the sumanene buckybowl, highlighting the major fields in which potential or real applications of sumanene have been demonstrated. Special attention is paid to sumanene-tethered functional supramolecular materials and architectures and ion-selective molecular receptors. Possible future trends in this emerging area are also discussed. Abstract Sumanene is a buckybowl molecule that is continuously attracting the attention of the scientific community because of its unique geometrical and physicochemical properties. This Minireview systematically summarizes advances and considerations regarding the applied supramolecular chemistry of sumanene. This work highlights the major fields in which potential or real applications of sumanene molecule have been reported to date, such as the design of sumanene-containing functional supramolecular materials and architectures, sumanene-based drug-delivery systems, or sumanene-tethered ion-selective molecular receptors. An assessment of the current status in the applied supramolecular chemistry of sumanene is provided, together with an emphasis on the key advances being made. Discussion on those milestones that are still to be achieved within this emerging field is also provided.

Published in: "Angewandte Chemie International Edition".

Trifluoromethylation of 2D Transition Metal Dichalcogenides: A Mild Functionalization and Tunable p‐Type Doping Method

2024-03-30T13:10:02+00:00March 30th, 2024|Categories: Publications|Tags: , |

Chemical modification is a powerful strategy for tuning the electronic properties of 2D semiconductors. Here we report the electrophilic trifluoromethylation of 2D WSe2 and MoS2 under mild conditions using the reagent trifluoromethyl thianthrenium triflate (TTT). Chemical characterization and density functional theory calculations reveal that the trifluoromethyl groups bind covalently to surface chalcogen atoms as well as oxygen substitution sites. Trifluoromethylation induces p-type doping in the underlying 2D material, enabling the modulation of charge transport and optical emission properties in WSe2. This work introduces a versatile and efficient method for tailoring the optical and electronic properties of 2D transition metal dichalcogenides.

Published in: "Angewandte Chemie International Edition".

Manipulation of the Self‐Assembly Morphology by Side‐Chain Engineering of Quinoxaline‐Substituted Organic Photothermal Molecules for Highly Efficient Solar‐Thermal Conversion and Applications

2024-03-29T13:08:10+00:00March 29th, 2024|Categories: Publications|Tags: |

Two organic molecules BQC and BQE with different substituents on the quinoxaline unit have been designed, with BQE having an ethyl group exhibiting efficient nonradiative decay. Moreover, the self-assembly property of BQE results in a textured surface and thus an efficient light-trapping system. A water-electricity cogeneration device based on BQE was fabricated and showed a water evaporation efficiency of 68 %. Abstract Organic photothermal materials have attracted increasing attention because of their structural diversity, flexibility, and compatibility. However, their energy conversion efficiency is limited owing to the narrow absorption spectrum, strong reflection/transmittance, and insufficient nonradiative decay. In this study, two quinoxaline-based D–A-D–A-D-type molecules with ethyl (BQE) or carboxylate (BQC) substituents were synthesized. Strong intramolecular charge transfer provided both molecules with a broad absorption range of 350–1000 nm. In addition, the high reorganization energy and weak molecular packing of BQE resulted in efficient nonradiative decay. More importantly, the self-assembly of BQE leads to a textured surface and enhances the light-trapping efficiency with significantly reduced light reflection/transmittance. Consequently, BQE achieved an impressive solar-thermal conversion efficiency of 18.16 % under 1.0 kW m−2 irradiation with good photobleaching resistance. Based on this knowledge, the water evaporation rate of 1.2 kg m−2 h−1 was attained for the BQE-based interfacial evaporation device with an efficiency of 83 % under 1.0 kW m−2 simulated sunlight. Finally, the synergetic integration of solar-steam and thermoelectric co-generation devices based on BQE was realized without significantly sacrificing solar-steam efficiency. This underscores the practical applications of BQE-based technology in effectively harnessing photothermal energy. This study provides new insights into the

Published in: "Angewandte Chemie International Edition".

Theoretical Prediction Leads to Synthesize GDY Supported InOx Quantum Dots for CO2 Reduction

2024-03-29T13:08:07+00:00March 29th, 2024|Categories: Publications|Tags: |

The preparation of formic acid by direct reduction of carbon dioxide is an important basis for the future chemical industry and is of great significance. Due to the serious shortage of highly active and selective electrocatalysts leading to the development of direct reduction of carbon dioxide is limited. Herein the target catalysts with high CO2RR activity and selectivity were identified by integrating DFT calculations and high-throughput screening and by using graphdiyne (GDY) supported metal oxides quantum dots (QDs) as the ideal model. It is theoretically predicted that GDY supported indium oxide QDs (i.e., InOx/GDY) is a new heterostructure electrocatalyst candidate with optimal CO2RR performance. The interfacial electronic strong interactions effectively regulate the surface charge distribution of QDs and affect the adsorption/desorption behavior of HCOO* intermediate during CO2RR to achieve highly efficient CO2 conversion. Based on the predicted composition and structure, we synthesized the advanced catalytic system, and demonstrates superior CO2-to-HCOOH conversion performance. The study presents an effective strategy for rational design of highly efficient heterostructure electrocatalysts to promote green chemical production.

Published in: "Angewandte Chemie International Edition".

Reductive Doping Inhibits the Formation of Isomerization‐Derived Structural Defects in N‐doped Poly(benzodifurandione) (n‐PBDF)

2024-03-28T13:08:12+00:00March 28th, 2024|Categories: Publications|

Reductive doping effectively prevents the creation of defects caused by structural changes (isomerization) during the production of n-doped poly(benzodifurandione) (n-PBDF). This process involves several mechanisms, including hydride transfer, the integer charge transfer, or the formation of charge transfer complexes, to stop structural isomerization. Abstract Recently, solution-processable n-doped poly(benzodifurandione) (n-PBDF) has been made through in-situ oxidative polymerization and reductive doping, which exhibited exceptionally high electrical conductivities and optical transparency. The discovery of n-PBDF is considered a breakthrough in the field of organic semiconductors. In the initial report, the possibility of structural defect formation in n-PBDF was proposed, based on the observation of structural isomerization from (E)-2H,2′H-[3,3′-bibenzofuranylidene]-2,2′-dione (isoxindigo) to chromeno[4,3-c]chromene-5,11-dione (dibenzonaphthyrone) in the dimer model reactions. In this study, we present clear evidence that structural isomerization is inhibited during polymerization. We reveal that the dimer (BFD1) and the trimer (BFD2) can be reductively doped by several mechanisms, including hydride transfer, forming charge transfer complexes (CTC) or undergoing an integer charge transfer (ICT) with reactants available during polymerization. Once the hydride transfer adducts, the CTC, or the ICT product forms, structural isomerization can be effectively prevented even at elevated temperatures. Our findings provide a mechanistic understanding of why isomerization-derived structural defects are absent in n-PBDF backbone. It lays a solid foundation for the future development of n-PBDF as a benchmark polymer for organic electronics and beyond.

Published in: "Angewandte Chemie International Edition".

Chelating Additive Regulating Zn‐Ion Solvation Chemistry for Highly Efficient Aqueous Zinc‐metal Battery

2024-03-28T13:08:10+00:00March 28th, 2024|Categories: Publications|Tags: |

Aqueous zinc-metal batteries (AZMBs) usually suffered from poor reversibility and limited lifespan because of serious water induced side-reactions, hydrogen evolution reactions (HER) and rampant zinc (Zn) dendrite growth. Reducing the content of water molecules within Zn-ion solvation sheaths can effectively suppress those inherent defects of AZMBs. In this work, we originally discovered that the two carbonyl groups of N-Acetyl-ε-caprolactam (N-ac) chelating ligand can serve as dual solvation sites to coordinate with Zn2+, thereby minimizing water molecules within Zn-ion solvation sheaths, and greatly inhibit water-induced side-reactions and HER. Moreover, the N-ac chelating additive can form a unique physical barrier interface on Zn surface, preventing the harmful contacting with water. In addition, the preferential adsorption of N-ac on Zn (002) facets can promote highly reversible and dendrite-free Zn2+ deposition. As a result, Zn//Cu half-cell within N-ac added electrolyte delivered ultra-high 99.89% Coulombic efficiency during 8000 cycles. Zn//Zn symmetric cells also demonstrated unprecedented long life of more than 9800 hours (over one year). Aqueous Zn//ZnV6O16·8H2O (Zn//ZVO) full-cell preserved 78% capacity even after ultra-long 2000 cycles. A more practical pouch-cell was also obtained (90.2% capacity after 100 cycles). This method offers a promising strategy for accelerating the development of highly efficient AZMBs.

Published in: "Angewandte Chemie International Edition".

Towards More Sustainable Aqueous Zinc‐Ion Batteries

2024-03-26T13:08:50+00:00March 26th, 2024|Categories: Publications|Tags: |

Aqueous zinc-ion batteries (AZIBs) are considered as the promising candidates for large-scale energy storage because of their high safety, low cost and environmental benignity. The large-scale applications of AZIBs will inevitably result in a large amount of spent AZIBs, which not only induce the waste of resources, but also pose environmental risks. Therefore, sustainable AZIBs have to be considered to minimize the risk of environmental pollution and maximize the utilization of spent compounds. Herein, this minireview focus on the sustainability of AZIBs from material design and recycling techniques. The structure and degradation mechanism of AZIBs are discussed to guide the recycling design of the materials. Subsequently, the sustainability of component materials in AZIBs is further analysed to pre-evaluate their recycling behaviors and mentor the selection of more sustainable component materials, including active materials in cathodes, Zn anodes, and aqueous electrolytes, respectively. According to the features of component materials, corresponding green and economic approaches are further proposed to realize the recycling of active materials in cathodes, Zn anodes and electrolytes, respectively. These advanced technologies endow the recycling of component materials with high efficiency and a closed-loop control, ensuring that AZIBs will be the promising candidates of sustainable energy storage devices.

Published in: "Angewandte Chemie International Edition".

NIR‐II Absorption/Fluorescence of D–A π‐Conjugated Polymers Composed of Strong Electron Acceptors Based on Boron‐Fused Azobenzene Complexes

2024-03-26T13:08:48+00:00March 26th, 2024|Categories: Publications|Tags: |

Luminescence in the second near-infrared (NIR-II, 1,000–1,700 nm) window is beneficial especially for deep tissue imaging and optical sensors because of intrinsic high permeability through various media. Strong electron-acceptors with low-lying lowest unoccupied molecular orbital (LUMO) energy levels are a crucial unit for donor–acceptor (D–A) π-conjugated polymers (CPs) with the NIR-II emission property, however, limited kinds of molecular skeletons are still available. Herein, D–A CPs involving fluorinated boron-fused azobenzene complexes (BAz) with enhanced electron-accepting properties are reported. Combination of fluorination at the azobenzene ligand and trifluoromethylation at the boron can effectively lower the LUMO energy level down to −4.42 eV, which is much lower than those of conventional strong electron-acceptors. The synthesized series of CPs showed excellent absorption/fluorescence property in solution over a wide NIR range including NIR-II. Furthermore, owing to the inherent solid-state emissive property of the BAz skeleton, obvious NIR-II fluorescence from the film (up to λFL = 1213 nm) and the nanoparticle in water (λFL = 1036 nm, brightness = up to 29 cm–1 M–1) were observed, proposing that our materials are applicable for developing next-generation of NIR-II luminescent materials.

Published in: "Angewandte Chemie International Edition".

Induced Chirality in Canthaxanthin Aggregates Reveals Multiple Levels of Supramolecular Organization

2024-03-23T13:07:59+00:00March 23rd, 2024|Categories: Publications|

Carotenoids tend to form supramolecular aggregates via non-covalent interactions where the chirality of individual molecules is amplified to the macroscopic level. We show that this can also be achieved for non-chiral carotenoid monomers interacting with polysaccharides. The chirality induction in canthaxanthin (CAX), caused by heparin (HP) and hyaluronic acid (HA), was monitored by chiroptical spectroscopy. Electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra indicated the presence of multiple carotenoid formations, such as H- and J-type aggregates. This is consistent with molecular dynamics (MD) and density functional theory (DFT) simulations of the supramolecular structures and their spectroscopic response.

Published in: "Angewandte Chemie International Edition".

Electro/Ni Dual‐Catalyzed Decarboxylative C(sp3)−C(sp2) Cross‐Coupling Reactions of Carboxylates and Aryl Bromide

2024-03-23T13:07:57+00:00March 23rd, 2024|Categories: Publications|

Paired redox-neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non-toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C−C cross-coupling reactions. Here, we report the electro/Ni dual-catalyzed redox-neutral decarboxylative C(sp3)−C(sp2) cross-coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar−Br bond by a NiI-bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2-phenoxy propionic acid, undergo oxidative decarboxylation to form carbon-based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)−C(sp2) cross-coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual-catalyzed cross-coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)−C(sp2) cross-coupling and represent a promising method for the construction of the C(sp3)−C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow-synthesis technology.

Published in: "Angewandte Chemie International Edition".

Intermediate Color Emission via Nanographenes with Organic Fluorophores

2024-03-23T13:07:55+00:00March 23rd, 2024|Categories: Publications|Tags: |

Nanographenes (NGs) produced by top-down methods carry multiple functional groups. We utilized this aspect for the reproduction of purple light by adding red- and blue-light emitting fluorophores. Based on our results, NGs can be utilized as carriers of fluorophores capable of generating intermediate colors of light. Abstract Photoluminescence (PL) color can be tuned by mixing fluorophores emitting the three primary colors in an appropriate ratio. When color tuning is achieved on a single substrate, we can simplify device structures. We demonstrated that nanographenes (NGs), which are graphene fragments with a size of tens of nanometers, could be utilized as carriers of fluorophores. The addition of red- and blue-light-emitting fluorophores on the edge successfully reproduced the purple light. The relative PL intensities of the fluorophores could be regulated by the excitation wavelength, enabling multicolor emission between blue and red light. Owing to the triphenylamine units of the fluorophores, the NGs showed PL enhancement due to aggregation. This characteristic was valuable for the fabrication of solid polymer materials. Specifically, the functionalized NGs can be dispersed into polyvinylidene difluoride. The resultant polymer films emitted red, blue, and purple color. Our study demonstrated the potential applicability of NGs for fluorophore carriers capable of reproducing intermediate colors of light.

Published in: "Angewandte Chemie International Edition".

Correspondence to “Structure of Violet Phosphorus and Its Phosphorene Exfoliation”

2024-03-23T13:07:50+00:00March 23rd, 2024|Categories: Publications|Tags: |

In 1865 Johann Wilhelm Hittorf discovered violet phosphorus and it took until 1969 when Thurn and Krebs determined the structure of orthogonally arranged tubes with pentagonal cross-sections. Different to their claim, the structure determined by Zhang et al. in 2020 depicted in orange is identical to the 1969 structure shown in green and should not be referenced as a new polymorph. Abstract The structure described in the publication “Structure of Violet Phosphorus and Its Phosphorene Exfoliation” (Angew. Chem. Int. Ed. 2020, 59, 1074–1080) is identical to the structure by Thurn and Krebs determined already in 1969 and therefore by no means a new modification.

Published in: "Angewandte Chemie International Edition".

Modular Weaving DNAzyme in Skeleton of DNA Nanocages for Photoactivatable Catalytic Activity Regulation

2024-03-23T13:07:49+00:00March 23rd, 2024|Categories: Publications|

A general approach is established for spatiotemporal control of DNAzyme-based gene regulation activity through modular weaving active DNAzyme into skeleton of tetrahedral DNA nanocages (TDN). The direct encoding of DNAzyme in TDN not only improves biostability and delivery efficiency, but also allows spatiotemporal control of their catalytic activity. Abstract DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light-triggered on-demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme-mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.

Published in: "Angewandte Chemie International Edition".

Investigating the Therapeutic Effects of Ferroptosis on Myocardial Ischemia‐Reperfusion Injury Using Dual‐Locking Mitochondrial Targeting Strategy

2024-03-22T13:08:36+00:00March 22nd, 2024|Categories: Publications|

Research of ferroptosis in myocardial ischemia/reperfusion injury (MIRI) using mitochondrial viscosity as a nexus holds great promise for MIRI therapeutics. However, high precision visualizing mitochondrial viscosity remains a formidable task owing to the debilitating electrostatic interaction caused by damaged mitochondrial membrane potential. Herein, we proposed a dual-locking mitochondrial targeting strategy that incorporates the idea of electrostatic forces and probe-protein molecular docking. Even in the damaged mitochondria, stable and precise visualization of mitochondrial viscosity in triggered and medicated MIRI was achieved owing to the sustained driving forces (pi-cation, pi-alkyl interactions etc.) between the developed probe CBS and mitochondrial membrane protein. Moreover, complemented by the western blot technology, we confirmed that ferrostatin-1 exerts its therapeutic effect on MIRI by improving the system xc−/GSH/GPX4 antioxidant system, confirming the therapeutic value of ferroptosis in MIRI. This work presents a new strategy for developing robust mitochondrial probes, thereby advancing the treatments for MIRI.

Published in: "Angewandte Chemie International Edition".

Discovery of Selective and Potent ATR Degrader for Exploration its Kinase‐Independent Functions in Acute Myeloid Leukemia Cells

2024-03-22T13:08:34+00:00March 22nd, 2024|Categories: Publications|

In the present work, a selective and potent ATR degrader was identified which was used as probe for explore the kinase-independent function of ATR. The results showed that ATR kinase inhibitor induced cell cycle arrest and inhibited the growth of AML cells. The ATR degrader was inclined to trigger immediate apoptosis in AML cells. A plausible explanation for this phenomenon is that ATR deletion induced nuclear envelope rupture, leading to genome instability, irreparable DNA damage. It causes to upregulate the level of p53 and subsequently triggers p53-mediated cell apoptosis. Abstract ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AML cells in vivo, unlike the ATR inhibitor. These results

Published in: "Angewandte Chemie International Edition".

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