搜索结果：Angewandte Chemie (International ed. in English)

In recent years, proximity-inducing drugs have emerged as a novel therapeutic modality that induces or stabilizes protein-protein interactions, especially by recruiting effector proteins to specific target proteins, thereby achieving functions beyond traditional inhibitors. The potential of proximity-inducing drugs extends beyond targeted protein degradation (TPD), as studies have demonstrated their ability to regulate biological processes such as signal transduction, gene transcription, chromatin regulation, and protein trafficking by modulating protein interaction networks. Rational discovery of proximity-inducing drugs requires clarifying their effects on protein-protein interactions, determining drug selectivity, and developing suitable ligands for drug construction. Proteomics has become a central technology in drug discovery, enabling global identification of the direct drug targets and systematic characterization of proteome-wide downstream responses. This provides a more refined map of drug mechanisms. In parallel, advances in machine learning applied to proteomic data, together with the expansion of proteome-wide ligandability maps, are further accelerating the discovery and optimization of proximity-inducing drugs. This review summarizes recent advances of proximity-inducing drugs, with a particular emphasis on how proteomics facilitates target space expansion, drug efficacy optimization, and ligandability discovery, alongside the emerging contributions of machine learning. Collectively, these insights aim to support the rational development of next-generation proximity-inducing drugs.

Fluorine chemistry has garnered attention for extending operating voltage limits of electrolytes through robust interfacial passivation owing to fluorine's strong electronegativity. However, confronted with solvent/salt/additive multicomponent induced vast combinatorial space, conventional high-voltage electrolyte recipe design has been confined to reliance on fluorine content adjustments, resulting in inevitable trade-off between oxidation stability and ion transport kinetics. Herein, we develop a Chemical Coordination-Informed Molarity feature parsing approach embedded into machine learning for training adapted models. By building the one-to-one mapping between components and chemical-coordination atomic molarities of a given recipe, the trained gradient boosting regression achieves a prediction of oxidation potential with MAE below 0.36 V. Demonstrating 2808 experiment operational candidates based on a ternary-solvent blend, we reveal the pronounced role of mono-coordinated fluorine and double-bonded oxygen molarity ratio (F1/O1) for breaking the oxidative stability limit, and define a golden design criterion for guiding O1-involved recipes: F1(≥8.19)/O1(≥13.39) ∈ $\in $ [0.55, 1.10]. Following this, we validate three experimentally reported low-fluoride recipes and identify two promising ones exhibiting oxidation potentials around 6.3 V vs. Li+/Li along with high ion-transport kinetics for further assessments. This work demonstrates customizable feature engineering in yielding intelligent materials design principles for reconciling multiple target performance that are usually mutually exclusive.

Developing intrinsically stretchable and healable semiconducting polymers with high charge-carrier mobility is critical for next-generation flexible electronics; however, integrating these conflicting functionalities remains a formidable challenge. Here, we report a "quadruple-hydrogen-bonds end-capping" strategy to realize high-performance stretchable and healable semiconducting polymers. By incorporating quadruple hydrogen-bonds between end-capping units linked with alkyl spacers into polymer backbone, we engineer a supramolecular architecture that achieves enhanced crystallinity and improved ordered packing with reduced π-π stacking distance, and also superior stretchabillity with molecular-ordering retention during stretching. Moreover, enhanced chain mobility together with dynamic and reversible and hydrogen-bonding sites in the architecture contribute to efficient healing. Consequently, our designed semiconducting polymer exhibits a more than 2-fold increase in mobility, while demonstrating stable mobility retention under strain, high mobility recovery after healing, and scalability in fully stretchable transistor arrays. This work provides an effective molecular design strategy for achieving simultaneous improvements in electrical performance, mechanical stretchability, and healing ability in organic electronics.

Understanding the intrinsic role of electronic structure in governing oxygen reduction reaction (ORR) activity on Pt-based catalysts remains a long-standing challenge due to the intrinsic coupling of electronic, strain, and ensemble effects in conventional alloy systems. Here, we establish a well-defined Pt-based nanowire (NW) model platform that enables the rigorous decoupling of electronic effects from structural contributions. By selectively incorporating electron-donating Re (PtRe) or electron-withdrawing Au (PtAu) into Pt NWs while maintaining identical morphology, surface structure, and coordination environment, the electronic contribution to ORR is isolated with minimal interference of strain and ensemble effects. A consistent activity trend (PtRe > Pt > PtAu) is observed from intrinsic ORR activity to device-level membrane electrode assembly performance. Crucially, a correlation is established between the electronic structure, intermediate adsorption behavior, and intrinsic activity. Meanwhile, the high-activity PtRe NW catalyst also delivers a robust durability with mass activity decline of 11.8% and voltage loss of 12 mV after 30,000-cycle tests. In situ spectroscopy and theoretical calculations results collectively confirm that Re dopants donate electrons to Pt, generating an electron-rich Pt surface that lowers the adsorption energy of oxygen intermediates and enhances ORR activity, while the Au dopant generates an opposite effect.

Interfacial water plays a crucial yet poorly understood role in the alkaline oxygen reduction reaction (ORR) by modulating the adsorption of oxygen intermediates and mediating proton-coupled electron transfer (PCET). However, the lack of techniques to dynamically correlate interfacial water with adsorbed intermediates makes it difficult to elucidate the mechanism governing the evolution of intermediate species. Here, we report a synchronized, site-consistent SERS-SEIRAS platform that tracks interfacial water and surface-adsorbed species (OOHad and OHad) in real time during cation-dependent ORR. Our results show that decreasing cation hydration energy induces the formation of an interfacial water layer with weak hydrogen bonding, low orientation constraints, and high dynamic flexibility, which diminishes its interactions with OOHad and OHad. This structure enhances water and oxygen transport and weakens OHad solvation, thereby reducing OHad coverage and accelerating the final PCET step. Our results reveal how cations reshape the interfacial hydrogen-bond network to control ORR kinetics. More broadly, this work demonstrates the power of multi-spectroscopic coupling for probing dynamic electrocatalytic interfaces and offers a strategy for improving catalyst performance via electrolyte and interface engineering.

The hydrogen production efficiency of hybrid seawater electrolysis devices hinges on high-performance catalytic materials with superior activity and chlorine corrosion resistance under the alkaline seawater conditions. However, the controllable modulation of catalyst structures to construct an effective anti-chlorine protective layer, one that simultaneously enhances both Cl corrosion resistance and anodic oxidation reaction activity, remains a formidable challenge. Herein, we report a phosphonyl-ligand engineering strategy that promotes the transformation of metal-organic frameworks (MOFs) into metal oxyhydroxides containing oxygen-anions during alkaline seawater ethanol oxidation reaction (EOR) with enhanced activity and Cl- corrosion resistance. Leveraging the tunable nature of organic ligands in MOFs provides a versatile platform for the in situ formation of oxygen anion layers with robust chlorine corrosion resistance. A phosphorus-containing MOF (Pa-Ni-TPA) was synthesized by partially substituting terephthalic acid (TPA) with 4-phosphonobenzoic acid (Pa). In contrast to the conventional MOF (Ni-TPA), the in situ generated metal oxyhydroxide from Pa-Ni-TPA incorporates PO4 3-. PO4 3- promotes the adsorption of ethanol and its intermediates onto nickel centers while inhibiting Cl adsorption, thereby significantly boosting both EOR activity and Cl corrosion resistance. These findings establish a detailed structure-performance correlation between MOF structural evolution and both catalytic activity toward alkaline seawater EOR and resistance to chlorine corrosion.

The intrinsic topological and electronic merits of graphitic carbon nitride (g‑C3N4) are fundamentally obscured by strong π-π stacking interactions and hydrogen-bonding interactions. Overcoming these noncovalent barriers without compromising the structural integrity remains a formidable chemical challenge. Herein, we report a targeted electrostatic decoupling strategy via protonation that rapidly unlocks the intralayer framework of g‑C3N4 into discrete, highly crystalline two-dimensional (2D) nanosheets under ambient conditions. By utilizing trifluoromethanesulfonic acid, selective protonation at the heterocyclic nitrogen sites induces pronounced interlayer electrostatic repulsion and simultaneous intralayer electronic reconstruction, achieving an unprecedented production efficiency of 200 mg·mL-1·h-1. Crucially, the high aspect ratio and structural fidelity of the as-exfoliated nanosheets enable unambiguous direct observation of the intrinsic lyotropic liquid-crystalline phase transition in pure g‑C3N4, resolving long-standing ambiguities regarding its mesoscopic assembly behavior. Furthermore, the 2D nanosheets display over 50-fold enhancement in photocatalytic hydrogen peroxide production activity compared to their bulk counterpart, attributed to the reduced thickness and significantly increased exposure of active sites. This work not only provides an efficient route for the exfoliation of layered polymers but also opens new opportunities for their solution-phase processing.

Since the discovery of carbon dots (CDs), the typical precursor combination of citric acid (CA)-urea has been widely used in the scientific community to explore the formation mechanism and luminescence behavior of CDs. However, there have only been a few reports on the synthesis of CDs featuring aggregation-induced emission (AIE) characteristics. In this study, CA and urea were used to synthesize hydrophilic red-emissive carbon dots (R-CDs) that exhibit blue fluorescence in water (dispersed state) and red fluorescence in DMF (aggregated state). The study reveals that the photoluminescence of R-CDs is governed by π-π stacking interactions between solute molecules as well as solvent effects between solute and solvent molecules, leading to solvent-responsive emission behavior. By tuning the solvent polarity, the intermolecular distance between R-CDs can be adjusted, thereby influencing their photoluminescent properties. Taking advantage of the solvent-responsive color change, anticounterfeiting printing and information encryption applications were designed. Moreover, by combining R-CDs with poly(vinyl alcohol) (PVA), hydrogel-based fluorescent information-encoding materials were successfully fabricated.

Aqueous Zn-S batteries have garnered significant attention for grid-scale storage but suffer from rapid capacity fade and sluggish reaction kinetics. Although existing strategies can improve redox reversibility, they fail to fundamentally address capacity attenuation arising from oxidation-driven ZnS decomposition loss. In this study, a nano-copper-based cathode/electrolyte interphase (Cu CEI) featuring a unique sulfur/ZnS dual-affinity is rationally designed to accelerate both S─S and Zn─S bond dynamics, effectively preventing ZnS accumulation and suppressing its decomposition via preferential Cu-ZnS binding. Specifically, the strong binding affinity of the Cu CEI stabilizes ZnS by reducing its direct contact with interfacial water. Meanwhile, the strong interaction between Cu nanoparticles and S8 activates ring-opening and facilitates S─S bond cleavage, elevating the discharge voltage to 0.75 V. Cu-mediated weakening of Zn─S bonds in ZnS synergistically lowers the apparent activation energy from 69.4 to 29.5 kJ mol-1, establishing a robust interfacial redox pathway with a low voltage hysteresis of 0.23 V. Consequently, the Cu CEI enables Zn-S system with excellent cycling stability over 1000 cycles at 5 A g-1 and a high areal capacity of ∼6.5 mAh cm-2 over 200 h in a pouch cell, underscoring the practical feasibility of this dual-affinity interphase design for high-performance Zn-S batteries.

Small-molecule drug discovery typically begins with the screening of compound libraries to identify initial hits, which are subsequently optimized into lead compounds and, ultimately, drug candidates. Diverse screening methodologies are employed, including DNA-encoded library technology, high-throughput screening, and fragment-based drug discovery (FBDD). Among these, FBDD is particularly powerful when integrated with structure-guided drug design and biophysical affinity measurements. However, accurately quantifying the weak binding affinities of fragments remains a significant challenge. To address this, we introduce chemical shift anisotropy K D $K_{\text{D}}$ (CSAKD), a novel method for determining absolute fragment affinities using 19 F $^{19}{\rm F}$ NMR relaxation. The CSAKD approach eliminates the need for titration experiments and isotopic labeling. Furthermore, we complement this method with a machine learning model for the rapid and accurate prediction of 19 F $^{19}{\rm F}$ chemical shielding tensors. In summary, CSAKD allows fast and efficient affinity determination which seamlessly integrates into FBDD by 19 F $^{19}{\rm F}$  NMR.

Aqueous zinc-iodine batteries (ZIBs) are promising for large-scale energy storage but suffer from interfacial challenges in wide pH and seawater electrolytes, such as polyiodide shuttling, chloride-induced pitting, and dendrite growth. This study proposes the engineering of micro-stepwise structures with exposed (100) facets via molecular modulation, which guides uniform distribution of zinc species preventing the formation of passivation layers in wide pH electrolytes. Additionally, the molecular layer reduces interfacial H2O activity via hydrogen bonds and physically blocks the migration of Cl- and polyiodides towards the anode, alleviating corrosion and pitting within seawater electrolytes. Benefiting from the coupling effect of micro-stepwise and molecular layers, the Ah-level Zn||I2 pouch cells deliver high capacities of 1.13 (2 mA cm-2) and 0.61 (4 mA cm-2) Ah after 110 and 1000 cycles in acidic electrolytes. The full cells also operate stably in acidic and alkaline electrolytes. It's worth noting that the Zn||I2 full cell delivers a high capacity of 180 mAh g-1 at 20 A g-1 after 20 000 cycles in seawater electrolyte. This study presents an effective interface engineering strategy for balancing long-term stability with rapid electrochemical reaction kinetics of ZIBs under diverse electrolyte scenarios.

Along with assessing chemical pathways, understanding the spatial evolution of deactivating coke species in zeolites is essential for enhancing their catalytic efficiency in processes for chemical and fuel production. In this study, synchrotron-based in situ X-ray photoemission spectroscopy experiments provide insights into the coke deposition on ZSM-5 catalysts with different Si/Al ratios during methanol-to-hydrocarbons conversion, which is an industrially relevant reaction. Surface-sensitive C 1s X-ray photoemission spectroscopy with a probing depth ≈1 nm demonstrates that the less acidic ZSM-5 zeolites exhibit a more pronounced coke accumulation on crystal surfaces and promote the formation of highly condensed, graphite-like structures than the higher acidic ones. Analysis of coking kinetics, lattice deformation, and coke composition using Raman, in situ infrared, and operando UV-vis spectroscopies further supports enhanced surface coking in low-acidity, slowly deactivating catalysts and more prominent micropore coke formation in high-acidity, fast-deactivating catalysts. The results indicate that acid site density governs both the kinetics and the preferential location of coke, shedding light on the fundamental nanoscale processes underlying coke-induced deactivation of zeolite catalysts.

Rechargeable Mg batteries represent an appealing post-lithium energy-storage technology, yet their advancement is hampered by the scarcity of cathode materials combining high capacity, rapid kinetics, and long-term cycling stability. In this study, we propose a molecular design strategy integrating extended endocyclic conjugation with polydentate Mg2+ coordination. Using hexaazatriphenylene (HATN), a rigid planar macrocycle featuring extensive π-conjugation and N,N-bidentate chelating sites, as the Mg-storage active center, we constructed polymer cathodes through monothioether and dithioether linkages. Theoretical and experimental analyses reveal that the HATN unit enables high-capacity, multi-electron reversible Mg2+ storage while maintaining structural stability via efficient charge buffering through strong electron delocalization, offering a notable advantage in a "capacity‒delocalization" evaluation framework. The thioether linkage suppresses dissolution and yields high surface area with hierarchical porosity, boosting interfacial kinetics and Mg2+ transport. The resulting polymer cathode delivers a high capacity of 370 mAh g‒1 at 0.1 A g‒1, superior rate capability (94 mAh g‒1 at 5.0 A g‒1), and exceptional cycling stability (95% capacity retention over 500 cycles at 1.0 A g‒1). This work presents an innovative molecular-level design strategy for high-performance organic Mg-battery cathodes, advances the mechanistic understanding of multivalent-ion storage, and provides a new paradigm for rational electrode engineering for multivalent battery systems.

Microbial artificial photosynthesis offers a promising strategy for light-driven biomanufacturing, yet its efficiency remains limited by the non-selective conversion of photogenerated electrons into metabolically usable reducing power, causing energy dissipation and weak coupling between light capture and metabolic reactions. Here, we report a rational strategy using riboflavin (RF), a membrane-permeable and biocompatible flavin photosensitizer, to selectively channel photonic energy into intracellular NADPH regeneration. Quantum chemical calculations and spectroscopic analyses reveal that light-excited RF exhibits a specific binding affinity and favorable electron transfer trend toward NADP+. In vivo, RF activation markedly elevated intracellular NADPH levels and enhanced the synthesis of NADPH-dependent metabolites through NADPH reductase-associated pathways. Transcriptomic and inhibition analyses linked RF-mediated NADPH regeneration to NADP+/NADPH redox enzymes rather than glucose-6-phosphate dehydrogenase-mediated flux, while NADH-related redox genes remained largely unaffected, demonstrating the selectivity of this reductive route. Cross-species and multi-product validations consistently reproduced these results, underscoring the generality of this mechanism across distinct NADPH-dependent microbial chassis. This work establishes a mechanistically defined and broadly applicable framework for directing photogenerated electrons into specific cellular reducing equivalents, paving the way for efficient artificial photosynthetic and bioelectrochemical platforms.

Ageing is inevitable and accompanied by progressive loss of skin elasticity. Fibroblasts, embedded within the extracellular matrix, finely regulate skin mechanics via membrane-bound ligands. Creating synthetic assemblies that mimic fibroblast function is appealing yet challenging. Here, we present a strategy that co-assembles lignin with divinyl ligands to generate fibroblast-mimicking polymersomes, enabling precise programming of bulk materials to emulate human skin across distinct physiological stages. Because lignin polymersomes are driven by relatively weak π-π stacking, hydrophobic ligands efficiently intercalate among aromatic rings, and their interfacial distribution can be tuned via molecular engineering. The polymersomes can be programmed in a Boolean logic‑gate manner (OR, AND, and NOT) to synthesize skin-mimetic gels with tailored mechanical properties, analogous to fibroblast behavior. Furthermore, the platform enables on‑demand, high‑resolution 3D printing of complex bioskin architectures. This work provides a biomimetic paradigm for the synthesis and precise control over assembly from the molecular to the macroscopic scale.

Despite the significance of hydrogen bonding in protein-carbohydrate interactions, carbohydrate conformation, and crystallinity (solubility), relative hydrogen bond donating capacities (HBDC) of individual alcohol groups of a given sugar are poorly characterised. Here the first systematic determination of the HBDC of individual sugar alcohol groups has been achieved, which were ranked in a HB-scale (pKAHY-scale) that is relevant for medicinal chemistry purposes. HB determination was achieved using an IR-based protocol with methyl α-glucoside- and α-galactoside-based model compounds that exclude any contributions from HB cooperativity effects. A wide variation in HBDC was found, especially for galactose, with a strong stereochemical dependence not only of the alcohol group itself, but also at adjacent and even remote positions. The glucose 4-OH and, notably, the galactose 6-OH groups were the strongest donors, whereas the glucose 2-OH and, notably, the galactose 4-OH groups were the weakest donors. Interestingly, the galactose 6-OH is the only group with a stronger HBDC than cyclohexanol. These differences could be qualitatively rationalised by a combined IR, NMR, and computational analysis, pointing to counteracting influences from inductive and the often multiple possible intramolecular hydrogen-bonding effects. The difference between the factors that determine carbohydrate HB donating capacities and Brønsted acidities is discussed.

Lanthanide (Ln)-doped perovskites show immense potential in luminescence. Although Ln2+ ions offer superior luminescence efficiency and spectral tunability over Ln3+, realizing Ln2+ luminescence remains a formidable challenge. Here, a novel strategy based on reduction potentials of 12 Ln3+ ions is developed to achieve selective reduction of Ln3+ to Ln2+ in CsCaCl3 using x-rays and mechanical force. Specifically, ions with lower reduction potentials (Eu3+, Yb3+, Sm3+) are reduced to the divalent state, whereas those with higher reduction potentials remain trivalent. Notably, the photoluminescence of Eu2+ increases by two orders of magnitude after x-ray irradiation. Meanwhile, non-reducible Ln3+ ions exhibit ultra-long persistent luminescence from the ultraviolet to near-infrared region, with Tb3+ showing a persistence time of 98 s (decay to 1/10 of its initial intensity) outperforming most commercial materials. Moreover, both Ln2+ and Ln3+ in CsCaCl3 exhibit bright mechanoluminescence. Mechanistic investigations identify Cs vacancies as hole traps and Cl vacancies as electron traps, governing carrier storage and release. Leveraging these properties, proof-of-concept applications are presented in radiation warning, collision detection, and x-ray imaging. This work establishes a multi-stimuli-responsive platform for valence-selective luminescence, opening new avenues for smart optoelectronic devices.

To address the limitations of conventional furan resins, which rely on furfural derivatives for synthesis and exhibit constrained performance, this work presents a catalytic polycondensation strategy that synthesizes high-performance resins directly from furfural and amines. Catalyzed by NH4Cl, the process transforms furan rings into pyrrole rings via a Schiff base intermediate, proceeding through aromaticity disruption, nitrogen-atom incorporation, and aromaticity reconstruction. This unreported mechanism constructs a multi-substituted pyrrole cross-linked network, which demonstrates exceptional thermal stability (450°C decomposition), flame retardancy (limiting oxygen index of 31.7%), superior mechanical strength (tensile strength of 70 MPa, flexural strength of 131 MPa), excellent fatigue resistance (a resin spring surviving 10 000 compression cycles at 95% strain), and robust adhesion to diverse substrates, particularly on stainless steel across an extremely broad temperature range (-196°C-200°C). The solvent-free, atom-economical method, coupled with dynamic covalent bonds enabling reprocessing, offers a sustainable pathway for biomass-based furfural utilization and establishes a general strategy for furan-to-pyrrole conversion with potential in engineering plastics, structural adhesives, and coatings.

Localized high-concentration electrolytes (LHCEs) have been identified as promising electrolyte formulations for lithium metal batteries, due to their effective interphase formation and promotion of compact Li deposition, yet their practical implementation is often limited by reduced ion transport kinetics. In this study, two industrially established fluorinated ethers are identified for the first time in battery research as effective co-diluents as they combine a broad electrochemical stability window with a low viscosity and intrinsic non-flammability. Incorporating these components, commonly used as heat transfer fluids, yields safer, less flammable electrolyte formulations with enhanced ion mobilities. In particular, the ternary co-diluent formulation shows improved ion mobility by reducing the electrolyte's viscosity while limiting excessive ion clustering. Based on the improved electrolyte transport kinetics, lower overvoltages and higher Coulombic efficiencies at current densities ≥ 1 mA cm-2 are achieved with the ternary co-diluent blend, resulting in markedly extended cycle life in an application-oriented zero-excess pouch cell compared with the baseline system. Complementary electrochemical and ex situ analysis of harvested electrodes at moderate current densities reveals no discernible differences in interphase morphology and composition, suggesting enhanced ion mobility as the primary cause of the improved high-rate performance.