All-carbon quaternary centers represent a fundamental structural unit found in a wide range of functional molecules. Within the versatile synthetic toolbox, the semipinacol rearrangement (SPR) stands as one of the most powerful tools for assembling this sterically congested motif. In this context, ‌radical-mediated SPR pathways‌, especially those entailing alkyl migrations, remain underexplored from a strategic standpoint. Herein, we report a visible light-promoted formal SPR of tertiary allyl alcohols using in situ-generated triplet nitrene species as the initiator under redox-neutral conditions. This method demonstrates broad substrate scope, enabling efficient construction of all-carbon quaternary centers across various steric environments, including rigid cyclic/spiro frameworks and flexible acyclic systems. Mechanistic investigations reveal substrate-dependent pathways: alkenyl cyclobutanols undergo triplet nitrene addition followed by concurrent ring-expansion and hydrogen atom transfer (HAT) to form cyclic ketones, while nonactivated allyl alcohols proceed through aziridination/ring-opening/SPR sequences to produce linear β-amino ketones. Preliminary biological assessments of these α-quaternary β-aminoketone derivatives revealed that compound 4a exhibited potent anti-DENV-2 activity, with an EC50 value of 0.95 ± 0.02 µM against viral replication.

Phototheranostic agents operating in the second near-infrared (NIR-II) window hold great potential for precision cancer therapy, yet the rational regulation of excited-state processes to simultaneously optimize fluorescence and phototherapeutic performances remains a fundamental challenge. Herein, we report a topology-driven excited-state engineering strategy for constructing conjugated oligomers with tailored excited-state manifolds and multi-channel excitation dynamics. By precisely manipulating molecular topology, conjugated topological oligomers achieve enhanced light-harvesting capability and optimized exciton utilization, thereby enabling synergistic regulation of excitation dynamics. Under 808 nm laser irradiation, nanoparticles (NPs) derived from TBT-3 exhibit 2.8-fold enhanced NIR-II fluorescence brightness, 2.7-fold improved photothermal performance, and 7.5-fold increased total reactive oxygen species (ROS) generation compared with TBT-1. In vivo studies demonstrate that TBT-3 NPs enable high-resolution NIR-II fluorescence imaging and efficient tumor elimination. Moreover, TBT-3-mediated phototherapy induces immunogenic cell death and enhances antitumor immunity, leading to improved therapeutic efficacy when combined with anti-PD-1 immune checkpoint blockade. This work provides a molecular topology-based strategy for manipulating excited-state landscapes and establishes conjugated oligomers as versatile candidates for NIR-II phototheranostics and cancer immunotherapy.

Bioorthogonality-activatable optical imaging activates caged or quenched probes via bioorthogonal reactions for disease diagnosis. Although chemiluminescence enables low-background detection, it has rarely been applied to bioorthogonality-activatable imaging. Here, we synthesize chemiluminescent tetrazine probes (CLTZs) by coupling a tetrazine acceptor to a phenoxy-1,2-dioxetane donor through π-conjugated vinylene linkers, enabling biomarker and bioorthogonality dual-locked activation for cancer urine testing. Unlike conventional chemiluminophores, tetrazine in CLTZs mediates an internal-conversion-to-a-dark-state quenching mechanism, suppressing chemiluminescence even after phenolate formation. Strong chemiluminescence is restored only when the phenolate form undergoes bioorthogonal reaction with bicyclononyne (BCN), generating pyridazine-containing donor-π-acceptor chemiluminophores. This unique dark state enables development of an H2O2 and bioorthogonality dual-locked probe ([H]BCP), emitting only when both H2O2 and BCN are present. By engineering BCN into a cancer-activatable bioorthogonal urinary reporter ([C]BUR) that releases renal-clearable BCN in tumors, a chemiluminescent bioorthogonal pair ([H]BCP & [C]BUR) is created. This pair achieves in vivo tumor imaging with a signal-to-background ratio of 438 and detects lung metastasis in early urinary assays with up to 23.9-fold signal enhancement over healthy mice. This work provides a molecular design for bioorthogonality-activatable chemiluminescence toward noninvasive, sensitive disease diagnosis.

Electrocatalytic nitric oxide reduction to ammonia (NORR) offers a dual opportunity for NO remediation and decentralized NH3 production, yet its efficiency is often limited by competing pathways and unclear structure-function relationships. Here we introduce a reactant-shunting strategy that installs a guiding electrocatalytic step via isolated Ru atoms to supply surface-bound [*]H species and enforce a Langmuir-Hinshelwood (LH) hydrogenation pathway. Using Ru1/Co3O4 as a model catalyst, we show that single Ru sites promote water adsorption and dissociation, forming stable Ru-H intermediates that thermodynamically and kinetically accelerate the coupling-hydrogenation steps in NORR. The optimized catalyst delivers an NH3 yield of 533.49 µmol cm[-2] h[-1] with a 97.19% faradaic efficiency, surpassing state-of-the-art systems. The reactant-shunting principle further generalizes across multiple oxide hosts, enhancing NH3 productivity by up to threefold. These findings establish pathway steering through controlled hydrogen delivery as a powerful strategy for high-efficiency electrocatalytic ammonia synthesis.

Functional nucleic acids (FNAs), including aptamers and DNAzymes, offer programmable recognition and catalysis for biosensing, but their performance in real samples is often compromised by nuclease degradation, matrix effects, and interface-associated losses. For diagnostic translation, stability must, therefore, be defined not only as strand persistence, but as retained folding, binding, catalysis, and signal generation under assay-relevant conditions. This review examines strategies for stabilizing FNAs in complex biological matrices and organizes the field around four design levers: Chemical, topological, architectural, and microenvironment/interface engineering. Chemical modification of sugars, backbones, and bases can reduce nuclease susceptibility, but requires functional validation. Topological approaches, including terminus shielding, circularization, covalent locking, and mechanically interlocked structures, limit strand accessibility, and reinforce functional conformations. Architectural strategies use multivalency, scaffolded presentation, DNA nanostructures, and rolling circle amplification-derived concatemers to improve robustness and signal retention. Microenvironment engineering further stabilizes FNAs through controlled immobilization, antifouling interfaces, nanomaterial-assisted protection, hydrogel or microgel confinement, and sample processing. Case studies in saliva, serum, urine, and stool illustrate how these levers can be combined to enable reliable FNA-based real-sample diagnostics.

Mn-based materials are widely used for syngas conversion, where MnO is generally regarded as the catalytically active phase under reducing conditions. Yet catalysts derived from different Mn oxide precursors often exhibit markedly different performances despite evolving into the same MnO bulk structure during reaction. Here we show that trace Mn[3+] sites stabilized on oxygen-deficient MnO surfaces serve as the decisive active sites. Time-resolved energy-dispersive x-ray absorption spectroscopy combined with iterative target transformation factor analysis and depth-resolved synchrotron photoemission spectroscopy reveals a persistent minor Mn3O4-like spectral contribution and its enrichment near the surface of Mn2O3-derived MnO. These stabilized sites strongly enhance CO adsorption and activation, thereby promoting C─O bond cleavage and markedly improving activity and selectivity for syngas-to-light-olefin conversion. More broadly, this work reveals how minority surface sites can govern catalytic function despite identical bulk phases and establishes an operando strategy for quantitatively resolving low-coverage active sites in reducible oxide catalysts.

A major bottleneck for the practical application of lithium-oxygen (Li-O2) batteries is the high overpotential resulting from sluggish kinetics of oxygen redox chemistry. This kinetic limitation can rise in part from the spin-state transition barriers in converting triplet oxygen ([3]O2) into peroxide species, alongside the parasitic generation of singlet oxygen ([1]O2). Here, we demonstrate that metal-support magnetic interactions can effectively overcome this spin barrier. Using palladium (Pd) nanoparticles anchored on ferrimagnetic CoFe2O4 (CFO) substrates as a model catalyst, we reveal that interfacial magnetic coupling restructures the spin and electronic states of Pd sites, generating spin-polarized active ensembles with optimized adsorption toward oxygen intermediates. This interfacial spin-electronic effect promotes the conversion of [3]O2 into peroxide species while suppressing parasitic [1]O2 evolution during charging, thereby improving the reversibility of oxygen redox chemistry. As a result, the Pd/CFO catalyst achieves a low charging overpotential of 0.05 V and remarkable energy efficiency (91.2%) under spin alignment. This finding establishes metal-support magnetic interaction as a powerful strategy for controlling spin-dependent oxygen electrocatalysis, providing a general design principle for catalysts involving multi-site interactions.

Electrocatalytic co-reduction of CO2 and NO3 [-] offers a low-carbon route to urea, yet practical deployment is constrained by unsatisfactory efficiency due to the absence of a quantitative, theory-guided catalyst design principle. In this study, we propose the generalized dipole moment (GDM) of active sites as a transferable descriptor guided by charge-locking asymmetric site polarization (CLASP) mechanism, that can quantify polarization strength correlated with selectivity prediction for catalysts. Constant-potential simulations show that increasing GDM strengthens *CO2 adsorption, promotes H2O dissociation, and progressively favors C─N coupling relative to the competing protonation pathway. The slow-growth method further tracks charge evolution along the *CO─*NO coupling coordinate, confirming that polarized active sites precharge *CO and facilitate the predominant C-to-N charge-redistribution tendency during formation of critical coupling intermediates. Guided by this descriptor, a series of Ln─Cu alloy catalysts were designed to validate the predicted scaling, with La─Cu as the best candidate.

Ferroelectric nematic (NF) liquid crystals are polar fluids that combine long-range orientational order with spontaneous macroscopic polarization and exceptionally large dielectric permittivity. While these properties make NF materials attractive for responsive soft devices, incorporating additional functionality remains challenging because polar order is highly sensitive to molecular mismatch. Here we introduce a molecular design strategy that enables optical control of NF materials using azobenzene-based mesogens structurally matched to the archetypal NF compound DIO. Two derivatives are themselves ferroelectric nematogens, demonstrating that photoisomerizable mesogens can intrinsically sustain and modulate NF polar order, with large and reversible light-induced changes in polarization and dielectric permittivity. The same structural matching principle also enables non-NF azobenzenes to co-assemble with DIO at concentrations up to 20 wt.% while preserving ferroelectric nematic order. In selected blends, light irradiation drives a reversible transition from the ferroelectric nematic state to a low-permittivity state consistent with antiferroelectric smectic order. Together, light and temperature provide complementary handles to navigate this phase landscape of competing ferroelectric and antiferroelectric order. These results provide a molecular design strategy for programming collective polar order in ferroelectric nematic fluids using light-responsive mesogens.

Direct electrochemical C-N coupling of abundant carbon and nitrogen feedstocks offers a sustainable route to glycine synthesis, yet achieving high efficiency remains challenging. Here, we develop an In-Bi catalyst by incorporating oxophilic indium (In) into a bismuth (Bi) matrix. During the co-reduction of oxalic acid and NO3 [-], the In-Bi catalyst delivers an exceptional Faradaic efficiency toward glycine (FEGlycine) of 83.3% with an industrial-level current density of 361.3 mA cm[-2], together with a glycine production rate of 4.3 mol h[-1] gcat. [-1]. It outperforms pristine Bi and previously reported state-of-the-art catalysts. Large-scale glycine electrosynthesis is further demonstrated over a 10 cm[2] In-Bi electrode, achieving a total current of 1.5 A with FEGlycine of 68.5% and yielding 1.4 g of glycine in 6 h. Mechanistically, oxalic acid and NO3 [-] first form glyoxylic acid oxime (GAO). Subsequently, In sites act as an "active hydrogen pump" to accelerate H2O dissociation, providing abundant surface-active hydrogen (*H) for efficient GAO hydrogenation to glycine. Meanwhile, the incorporation of In modulates the electronic structure of the Bi matrix, enhancing GAO adsorption and electron transfer. The synergistic regulation of *H supply and electronic structure accelerates the conversion of GAO to glycine, resulting in superior performance of In-Bi.

Red-emissive carbon dots (R-CDs) hold promise for bioimaging and optoelectronics, yet their synthesis under mild, scalable conditions remains challenging. Conventional hydrothermal routes demand high temperature and pressure, while ambient-pressure alternatives rely on strong acids and yield limited quantum yields without programmable surface control. This work reports a catechol-assisted ambient-pressure strategy that achieves hundred-gram-scale preparation of R-CDs by simple heating at ∼90°C. Catechol acts as a co-polymerization mediator, participating in formation of carbon dots while its dual hydrogen-bonding network suppresses functional-group detachment, stabilizes radical intermediates, and lowers the steric barrier for cyclization. This mechanism enables programmable tuning of hydrophilicity/hydrophobicity and emission wavelength by varying the precursor substituents. The hydrophobic carbon dots exhibit a solid-state quantum yield of 45.26% (encapsulated in polyvinylpyrrolidone), the highest reported, and enable white light-emitting diodes (WLED) with a color rendering index (CRI) of 94. The hydrophilic carbon dots (quantum yield 37.86%) are directly applied to deep-tissue in vivo imaging without surface modification. This work provides a versatile molecular engineering platform for sustainable synthesis of functional aromatic carbon nanomaterials.

Medium-sized rings and macrocycles constitute a privileged class of scaffolds in medicinal chemistry, providing unique access to challenging biological targets through their preorganized, semi-rigid architectures. However, their synthesis remains challenging due to the unfavorable kinetic and thermodynamic constraints during ring closure. Herein, we report the efficient cyclization of ω-isocyano aldehydes via Passerini and Ugi multicomponent reactions (MCRs), alongside related variants. These transformations provide rapid access to structurally diverse medium-sized and macrocyclic α-acyloxy, α-hydroxy, α-acetamido, and α-keto lactams, as well as tetrazole-fused macrocycles, under mild conditions. Notably, this macrocyclization strategy relies on C(sp[3])─C(sp[2]) bond formation while simultaneously generating α-functionalized amide motifs. By avoiding the need to pre-synthesize α-functionalized carboxylic acids, this approach offers a complementary alternative to traditional macrolactamization.

Iron bisphosphine complexes represent an important class of sustainable catalysts for a variety of important chemical transformations due to the high abundance, low toxicity, and redox-rich chemistry inherent to iron-based systems. In particular, transient, low-coordinate Fe(I) species are postulated to play a pivotal role in multiple catalytic transformations as the principal species for C─X bond activation (X = Cl, Br, I). However, insight into the electronic structure, bonding, and reactivity of Fe(I)-bisphosphine complexes remains poorly developed. In the present study, we report the development of four-coordinate (4C), high-spin (S = 3/2) Fe(I)-bisphosphine-ates. Several novel Fe(I) complexes were structurally characterized, and their electronic structure and bonding were evaluated using a combined spectroscopic, synthetic, and computational approach. Additionally, this study highlights the potential role of charged species in synthetically relevant contexts via in situ formation of (4C) Fe(I)-bisphosphine-ates in the presence of ubiquitous additives (e.g. MgBr2). Lastly, we demonstrate the utility of these Fe(I)-bisphosphine-ates toward rapid C─X homolytic cleavage of common alkyl- and aryl-halide electrophiles, as well as the ability to serve as synthons for further development of new high-spin Fe(I)-bisphosphine-ate complexes through transmetalation.

The controllable regulation of dimensionality and interpenetration in covalent organic frameworks (COFs) is crucial for optimizing photocatalytic performance, yet the translation of 3D COFs from structural construction to functional customization remains challenging. Here, we successfully designed a series of mortise-and-tenon molecular joint COFs by rationally engineering a twisted tetraphthaldehyde ligand bearing π-conjugated "clips". Stepwise extension of the "clips" enables topological evolution from 2D to twofold interpenetrated 3D, and ultimately to noninterpenetrated 3D structure. Notably, DHP-CuPor-COF with noninterpenetrated 3D structure amplifies light-harvesting efficiency and substrate accessibility, enabling superior photothermal conversion and catalytic performance over its 2D and twofold interpenetrated 3D counterparts. To the best of our knowledge, it delivers highly efficient photothermal-catalytic C─X (X = O, S) bond formation for selective transformation of phenolic compounds via cross-dehydrogenative coupling (CDC) reactions (conv., >90% and yield, >80%), markedly outperforming conventional thermal catalysis. The high efficiency arises from the synergistic of open 3D channels, abundant Cu-porphyrin active sites and strong photothermal effect. This work provides an innovative strategy to tune the topological chemistry of COFs for advanced photocatalytic applications.

Restricting amino acid diversity is expected to impair enzyme catalysis, but whether such constraints simply diminish catalytic activity or generate distinct catalytic chemistry remains unclear. We reconstructed an ancestral nucleoside diphosphate kinase (NDK) scaffold using 10 prebiotically plausible residues plus lysine and arginine. The resulting variant, Arc1-12KR, retained the canonical NDK fold in its crystal structure despite lacking the catalytic histidine. Chromatographic and mass spectrometric analyses showed ADP disproportionation to ATP and AMP, an activity undetectable in the NDK scaffold prior to amino acid reduction. Kinetic analysis showed nonlinear dependence on ADP concentration, and docking/molecular dynamics simulations indicated that the putative active-site region can accommodate two ADP molecules. These structural, computational, and mutational analyses suggest that compositional constraints reshape ATP-forming phosphoryl-transfer chemistry through a reorganized active site in which aspartate and arginine, together with coordinated Mg[2+], may enable phosphoryl transfer via a noncanonical, histidine-independent mechanism. Despite modest catalytic efficiency, this activity represents a viable catalytic solution under compositional constraints, demonstrating that ATP formation can be supported by minimal amino acid repertoires. Thus, restricting amino acid diversity can generate distinct yet convergent ATP-forming catalytic solutions, which may represent chemically plausible early routes to ATP formation under primitive conditions.