Olefins are widely present in natural products and synthetic drugs, and also serve as building blocks in organic synthesis. However, deuterated multisubstituted alkenes are rarely reported, owing to structural limitations for the reduction of corresponding alkynes and a lack of efficient hydrogen isotope exchange methods for such alkenes caused by steric hindrance. Herein, we have developed an efficient and convenient zeolite-catalyzed hydrogen isotope exchange reaction for multisubstituted olefins via reversible addition of protons to alkenes in D2O solvent. This novel approach affords a wide range of deuterated multisubstituted alkenes through a simple separation operation with the use of commercially available catalysts and D2O.

Nickel-catalyzed cross-electrophile coupling (XEC) has emerged as an efficient and economical strategy for constructing C-C bonds, a pivotal transformation in diversifying molecular architectures. However, conventional XEC methodologies typically rely on stoichiometric metallic reductants, which present inherent challenges, including safety risks, operational instability, and environmental concerns. Although electrochemical XEC in undivided cells circumvents the need for chemical reductants, it remains constrained by environmental issues and chemoselectivity limitations due to its dependence on sacrificial metal anodes or stoichiometric organic donors to supply electrons for cathodic reduction. Herein, we report a nickel-catalyzed electrochemical cross-electrophile coupling paired with water oxidation. By utilizing water as a sacrificial electron donor, this electrochemical platform facilitates the versatile construction of diverse C-C bonds, including Csp2-Csp3, Csp3-Csp3, and Csp-Csp3 linkages, from readily accessible aryl, alkenyl, alkynyl, and alkyl halide electrophiles, affording products in yields up to 99%. The undivided cell configuration markedly reduces system complexity, lowers capital costs, and supports scalable electrochemical synthesis. Moreover, this electroreductive coupling strategy exhibits broad functional group tolerance and is amenable to the late-stage derivatization of complex drugs and natural products. This operationally simple, electricity-driven approach offers a versatile platform for C-C bond formation.

Deuterium labelling has been a vital tool in chemical, pharmaceutical, and biological research for many years. Recently, there has been a surge of interest in its applications in emerging fields such as deuterium metabolic imaging (DMI) and luminescent material development. The demand for deuteration of organic compounds has increased significantly, resulting in the development of various heterogeneous catalytic deuteration methodologies, including nanocatalysis and electrocatalysis, over the past five years. Notably, many of these deuteration reactions utilize relatively inexpensive, environmentally friendly, and safe D2O, which enhances operational convenience. This review aims to summarize recent advancements in heterogeneous catalytic deuteration using D2O and to highlight innovative applications of deuterium labelling, including deuterium metabolic imaging, deuterated luminescent materials, and quantitative mass spectrometry.

Perdeuterated compounds are essential in various fields, including the development of deuterated pharmaceuticals and stable isotope-labeled internal standards (SIL-IS). The reductive perdeuteration of alkenes offers an economical and efficient method to obtain alkanes with multiple deuterium atoms. Despite progress in heterogeneous catalytic reductive deuteration of alkenes, the perdeuteration analogue remains elusive, mainly due to difficulties in generating controllable surface-active deuterium species, which are necessary for efficient and selective labeling. Herein, we present an electrochemical strategy for the reductive perdeuteration of alkenes using Rh nanoparticles and D2O as the deuterium source. Thioalcohol serves as a crucial additive that modifies Rh nanoparticles, enhancing deuterium incorporation from 2 to 5 D atoms per molecule. Mechanistic studies reveal that thioalcohol functions as a sulfur anion coordinating with the nanoparticles during the reaction, suppressing reductive deuteration while significantly improving both the H-D exchange between Rh-D and alkenes, and the regeneration of Rh-D from Rh-H and D2O. This method demonstrates high site-selectivity for both aryl and alkyl alkenes, and is broadly effective with alkenes of varying electronic character. The strategy can be readily applied to the synthesis of deuterated pharmaceuticals, typically yielding products with over 4.0 deuterium atoms per molecule, thus providing a rapid and cost-effective pathway for practical SIL-IS applications.

Organic electrosynthesis offers a sustainable platform for redox transformation under mild conditions, where radical intermediates play pivotal roles. However, direct structural characterization of these transient species remains challenging, particularly under operando conditions, hindering mechanistic understanding and reaction design. Herein, via digital light processing (DLP) 3D-print technology, we have designed the electrolytic flat cell for operando electron paramagnetic resonance (EPR) tests to track radical intermediates in real time. This architecture ensures precise electrode positioning within tailored channels, which could increase the electrodes' overlap area to reduce the resistance and improve the signal-to-noise ratio, alongside good mechanical robustness with low fabrication costs. Through time-resolved EPR technology, the formation order of amino and phenolic radicals has been demonstrated, confirming the radical addition of phenothiazine N-centered radical to p-methoxyphenol in C-N cross-coupling; Two resonance structures of benzenesulfonamide, the aryl pi radical and N-centered radical, could be distinguished by EPR analysis, which helps to clarify the chemo- and regioselectivity in (3 + 2) annulation; Solvent-mediated radical rearrangement inspired the design of a selective C-O cross-coupling between diphenylamine and phenol, demonstrating the importance of confirming intermediate structure for reaction design. Given the universality of this in-situ EPR platform, we believe it provides robust support for monitoring active intermediates in electrochemical reactions and elucidating reaction mechanisms.

Malignant tumors remain a leading cause of premature death worldwide, with disproportionately increasing burdens in resource-limited regions. Although immune checkpoint blockade (ICB) has emerged as a transformative cancer therapy, its efficacy is often limited by the immunosuppressive tumor microenvironment (TME). Leveraging iron as the most abundant bioactive transition metal in Earth's crust, we report F-Fe, a complex IV-targeted carbon monoxide-releasing molecule (CORM) that is activated by a clinically approved dental light-curing unit to induce pyroptosis for reprogramming the TME. We developed a bioinspired delivery system named GLEAM to facilitate clinical applications that adhere to tissue surfaces while channeling light into deeper tissue for on-target CO release, simultaneously providing real-time visual feedback for treatment monitoring. Murine oral and breast cancer models validated the therapeutic efficacy, showing significant tumor suppression and TME remodeling. When combined with anti-PD-1 antibody (aPD-1) therapy, it markedly suppressed metastasis, prevented recurrence, and prolonged survival. Our findings suggest that Fe-based small molecules with biomimetic delivery can leverage dental light to boost ICB efficacy, offering a sustainable and translational approach to tumor treatment.

Cancer immunotherapy holds promise for improving the efficacy of cancer treatment; however, low response rates remain a considerable challenge. Photodynamic therapy has a potential to be effective in immunotherapy, but it is limited by the inabilities to target tumor and limitation of reactive oxygen species (ROS) generation by hypoxia. Here, mitochondria-targeted zinc phthalocyanines (ZnPcs) are developed to precisely induce pyroptosis and activate immune responses. Cationic moieties incorporated in the ZnPc core allow strong localization in the mitochondrion and avoid aggregation of ZnPc, which serves as the highest site-specific production of ROS through the irradiation process. ZnPc-4 is among the synthesized derivatives that inhibit oxidative phosphorylation, relieving hypoxia and increasing type I/II ROS to cause mitochondrial dysfunction, which eventually triggers pyroptosis. Encapsulation of ZnPc-4 within DSPE-PEG2000-cRGDfk nanoparticle (ZnPc-NP) enhances its tumor-targeted capability and biocompatibility. In vivo, ZnPc-NP triggers immunogenic pyroptosis, eliciting potent anti-tumor immunity. In addition, ZnPc-NP combines with αPD-1, significantly inhibiting tumor metastasis and recurrence. This study establishes a dual-targeted photodynamic platform that overcomes microenvironmental constraints to potentiate cancer immunotherapy.

Organic electrosynthesis is a versatile and evergreen tool for constructing chemical compounds. However, the study of highly active electrodes has not received enough attention, which limits the further development of organic electrosynthesis. This work introduces a bottom-up route to prepare chitin-derived composite carbon aerogel electrodes (CCAEs), which can be directly used as electrodes in organic electrosynthesis systems. Various metal nanoparticles, such as Pt, Pd, RuO2, Cu and Ni, are well confined in these free-standing and porous CCAEs (M-CCAEs). The linear sweep voltammetry and in-situ Raman tests under electrochemical conditions show that RuO2-CCAEs possess good electrochemical oxidation ability for chlorine anions and good stabilizing effect on the generated chlorine radicals, which can serve as a mediator for the electrochemical C(sp3)-H activation. The combination of M-CCAEs with mediators achieves a series of electrochemical oxidative C(sp3)-H chlorination, bromination, nitration and etherification. Moreover, M-CCAEs promote the electrochemical hydrogen isotope exchange reaction of some important drug molecule structures, such as Ibuprofen, Diclofenac and Zolpidem.

Selective functionalization and high-value conversion of polyfluoroalkyl compounds is of paramount importance due to their widespread use in pharmaceuticals, agrochemicals, and advanced materials. However, the formidable stability of C(sp3)-F bonds, exacerbated by strong electron-withdrawing effects, steric hindrance, and the inherent challenge of achieving precise selectivity, has significantly hampered efforts toward their controlled activation and modification. Herein, we present a dual photoredox/cobalt catalytic strategy that enables redox-driven defluoroallylation of perfluoroalkylarenes and polyfluorinated aliphatic amides. Our approach leverages single-electron reduction to cleave robust C(sp3)-F bonds, generating reactive perfluoroalkyl radicals that couple efficiently with simple alkenes. Cobalt-mediated hydrogen atom transfer, with Lewis acidic fluorine scavengers serving primarily to trap the fluoride and suppress back-electron transfer, ensures precise regioselective allylation under mild conditions. Mechanistic investigations reveal that controlled radical generation and selective activation underpin the unique site selectivity observed. This dual catalytic platform offers an efficient strategy for the construction of complex fluorinated scaffolds and expands the toolkit for the selective transformation of polyfluorinated frameworks.

Sulfur dioxide (SO2) is a widespread industrial pollutant from fossil fuel combustion and metal smelting that causes serious environmental and health concerns. Converting SO2 into valuable chemicals provides a sustainable solution for emission mitigation and resource use. Here we show a paired electrolysis strategy that directly transforms SO2 into cyclic sulfite esters—high-value organosulfur intermediates widely used in organic synthesis and as precursors for functional materials—under mild conditions. SO2 is reduced at the cathode to elemental sulfur, which then undergoes anodic oxidation and couples with alcohols to form five-membered, six-membered and seven-membered cyclic sulfite esters. Mechanistic studies reveal key sulfur-containing intermediates and elucidate the critical redox pathways. This method efficiently converts even low concentrations of SO2, including simulated industrial flue gas, demonstrating practical applicability. The strategy provides a versatile and environmentally friendly platform for green organosulfur synthesis and pollutant valorization, opening new avenues for sustainable chemical manufacturing. Paired electrolysis converts industrial SO2 directly into valuable cyclic sulfite esters, turning a common pollutant into useful chemicals. Mechanistic studies reveal key intermediates, offering a sustainable and versatile platform for green organosulfur synthesis and pollutant valorization.

Alkynyl thioethers are versatile intermediates in organic synthesis, and a synthetic strategy involving C-H/S-H oxidative cross-coupling is atom-economical and effective. However, the homocoupling of alkynes is hard to be prevented under aerobic conditions. Herein, we report an oxygen-free electrochemical oxidative coupling of terminal alkynes with thiophenols via an alternating current (AC) electrosynthesis. This approach stabilizes active Cu species and suppresses copper deposition via precisely controlling current, frequency, and duty ratio. The method affords up to 83% yields without external oxidants and ligands and minimizes undesired homocoupling and overoxidation. Mechanistic studies have confirmed that disulfide mediates the single-electron oxidation of the alkynyl copper intermediates.

The defluorination-enabled functionalization not only provides an effective strategy to mitigate fluoride pollution, but also opens new avenues for constructing molecular diversity. Although numerous methods for C-F bond activation have been developed, their applications are typically confined to single defluorination-monofunctionalization processes. Traditional approaches to achieve 1,1-dual modification rely on multistep reaction sequences or precious-metal catalytic systems, which suffer from inefficiency, high cost, and significant environmental burden. In this study, we report the first electroreductive strategy for one-pot 1,1-deuterocarboxylation of C(sp3)-F bonds using cost-effective deuterium oxide (D2O) as the deuterium source and carbon dioxide (CO2) as a sustainable C1 feedstock. This method demonstrates broad substrate compatibility with difluoro-/trifluoroalkylarenes and enables late-stage drug functionalization without pre-activation. Mechanistic studies confirmed that the reaction proceeds via a sequential pathway: the substrate undergoes initial reduction at the cathode, reacts with CO2, and then undergoes reduction by deuterium protonation in the presence of D2O, ultimately leading to the formation of the final product.

Carbon-carbon bonds are the most frequently encountered bonds in drugs, natural products, agrichemicals, and perfumes. This makes reactions that can access C-C bonds, particularly those that access sterically complex architectures, of high impact to multiple industries and applications. Common C-C bond-forming reactions such as the Suzuki coupling or Diels-Alder cycloaddition have revolutionized synthesis, yet the building blocks required to perform these reactions, such as boronic acids or dienes, are only available in modest diversity from commercial suppliers compared to other common building blocks. A reaction that makes densely functionalized C-C bonds from broadly available starting materials would facilitate deeper access into chemical space. Here, we demonstrate an sp(3)-sp(3) C-C coupling method that uses amines and carboxylic acids, which are among the most broadly available building blocks in vendor catalogs. Our method achieves the coupling of tertiary carbon centers to access dense carbon architectures including from complex pharmaceutical and natural product substrates. Preactivation of both the amine and acid functional groups enables an iron catalyst to unite the carbon-based building blocks under reducing conditions, which were identified using high-throughput experimentation. Extensive electron paramagnetic resonance measurements highlight the intermediacy of radicals and the spin state transformation of iron during the reaction. Our amine-acid coupling establishes a method for navigating chemical space that complements the current toolbox of carbon-carbon bond-forming reactions.

Electrochemical oxidative C-N bond formation of olefins provides a sustainable route to nitrogen-containing molecules, enabling direct C-N bond formation under oxidant- and metal-free conditions. Despite recent progress, the mechanistic diversity of these reactions and the factors governing pathway selectivity remain poorly understood. Herein, we show that the relative oxidation potentials of olefins and sulfonamides dictate distinct C-N bond-forming modes: nucleophilic attack of sulfonamides on olefin radical cations when the olefin is more readily oxidized, nitrogen radical addition when the sulfonamide is preferentially oxidized, and radical-radical cross-coupling when the redox properties are comparable. In situ electrochemical electron paramagnetic resonance spectroscopy provides direct structural evidence for key radical intermediates, offering rare mechanistic insight into these transformations. Guided by this framework, we developed an electrochemical annulation that affords pyrrolidines and an allylic C-N bond formation process, demonstrating the synthetic utility of pathway control. By correlating substrate redox properties with reactivity outcomes, this work establishes principles for selectivity in the electrochemical olefin C-N bond formation reaction and demonstrates the broader potential of electrochemistry in efficient C-N bond construction.

Sulfur anions have emerged as promising photosensitizers for light-driven single-electron transfer (SET) chemistry. Established mechanistic pictures typically invoke substrate preassociation, either through electron donor-acceptor (EDA) complexation or via covalent adduct formation. Recent reports, however, describe sulfur-anion systems that operate efficiently in the apparent absence of these canonical pathways, highlighting an unresolved role for the intrinsic excited-state properties of sulfur anions. Here, we map the photochemical cycle of a representative sulfur-anion, PC3-S-, photosensitizer by combining optical and magnetic spectroscopies. We show that its absorption originates from intramolecular charge-transfer (ICT) transitions and can be shifted into the visible region through π-system extension. Time-resolved measurements indicate that static and dynamic electron-transfer pathways can coexist, with the dominant route depending on substrate identity. In particular, polycyclic aromatic substrates favor static quenching, correlating with markedly faster reactions. In the investigation of light-induced reductive dehalogenation functionalization reactions, PC3-S- demonstrated higher catalytic efficiency, in which TON up to 248 with 0.4 mol % loading. The data are consistent with non-covalent pre-association that leaves the sensitizer's intrinsic energy-level landscape largely unchanged, raising the possibility of anti-Kasha reactivity. Together, these findings provide spectroscopic constraints on bimolecular charge-transfer mechanisms of sulfur-anion photosensitizers and offer design principles for more efficient photocatalytic SET processes.

Trivalent phosphines bearing P-X bonds are valuable intermediates, antioxidants, ligands, and functional agents, yet their sustainable and selective synthesis remains challenging. Here we present a synchronous identification strategy for P-intermediates and nucleophiles that enables oxidant-free electrochemical P-H/X-H cross-coupling to P(iii) phosphines. Combined CV, EPR, 31P NMR sampling, and in situ mass spectrometry analyses reveal the stepwise conversion of P-H species into P-centered radicals, bisphosphine intermediates, and bisphosphine radical cation intermediates. These intermediates are selectively recognized by N-H, S-H, or O-H nucleophiles, directing the formation of P-N, P-S, and P-O bonds. One to three P-X bonds can be installed in a single operation from diverse X-H partners, affording bi- and multidentate trivalent phosphines with high selectivity. This mechanistically guided platform offers a sustainable and programmable route to functional trivalent phosphorus, thereby broadening the synthetic toolbox for trivalent phosphorus design.

Although significant developments are made in non-noble metal catalysts for N-alkylation of nitroarenes with alcohols via borrowing hydrogen strategy, obtaining catalysts with superior activity, reusability and broad substrate scope under mild reaction conditions remains challenging. Single-atom catalysts (SACs) hold unique coordination/electron structures, to be the potential candidates for this reaction. In this study, we firstly and creatively fabricate bio-inspired Zn SACs with asymmetric Zn-N2O2 sites by utilizing the natural skeleton of biomass chitosan (denoted as Zn/CS), and achieve the first instance of heterogeneous Zn SACs in borrowing hydrogen reaction between nitroarenes and alcohols. The results reveal that the asymmetric Zn-N2O2 sites induced by natural skeleton (like ligands) and nanoporous structure of Zn/CS significantly promote the N-alkylation efficiency of nitroarenes with alcohols. Notably, the Zn/CS exhibits the highest turnover frequency (TOF) among the reported heterogeneous catalysts, as well as wide substrate scope (56 examples) and excellent reusability. Furthermore, the catalytic pathway/mechanism is investigated by combing theoretical calculations, which reveals that the asymmetric Zn-N2O2 sites with electron-deficient character can facilitate the formation of Zn-H and Zn-O bonds between Zn/CS and Ph-CH2O-, thus easily generating the transition state Ph-CH2O* and driving the whole reaction.

As fundamental chemicals, alkynes have been pivotal in synthesizing numerous value-added compounds. Direct manipulation of alkynes offers rapid access to diverse chemical spaces. Cleaving the alkyne triple bond has traditionally required harsh conditions due to its high bond dissociation energy. Here, we present a manganese-catalyzed electrochemical nitrogenation method for the direct cleavage of C equivalent to C bonds, efficiently generating various nitriles under mild conditions. This reaction demonstrates extensive functional group tolerance and eliminates the need for stoichiometric chemical oxidants. CV experiments verified the role of Mn catalysis, and the N3 radical intermediate was confirmed by EPR spectroscopy. Our synthetic protocol provides a promising and versatile alternative for constructing nitrogen-containing compounds, potentially transforming approaches in chemical synthesis (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.