Abstract Reticular chemistry has enabled the synthesis of tens of thousands of metal–organic frameworks (MOFs), yet the discovery of new materials still relies largely on intuition-driven linker design and iterative experimentation. As a result, researchers explore only a small fraction of the vast chemical space accessible to reticular materials, limiting the systematic discovery of frameworks with targeted properties. Here, we introduce NexerraR1, a building-block chemical language model that enables inverse design in reticular chemistry through targeted generation of organic linkers. Rather than generating complete frameworks directly, Nexerra operates at the level of molecular building blocks, preserving the modular logic that underpins reticular synthesis. The model supports both unconstrained generation of low-connectivity linkers and scaffold-constrained design of symmetric multidentate motifs compatible with predefined nodes and topologies. We further combine linker generation with flow-guided distributional targeting to steer the generative process toward application-relevant objectives while maintaining chemical validity and assembly feasibility. The generated linkers are subsequently assembled into three-dimensional frameworks and structurally optimized to produce candidate materials compatible with experimental synthesis. Using NexerraR1, we validate this strategy by rediscovering known MOFs and by proposing the experimental synthesis of a previously unreported framework, CU-525, generated in silico. Together, these results establish a controllable building-block-level design framework for reticular chemistry in which chemical language modeling enables the direct translation from computational design to synthesizable frameworks.
Abstract Anode-free Zn batteries are attractive for zero-excess-Zn operation and maximized anode utilization, but reversible high-areal-capacity Zn plating/stripping over large hostless interfaces remains difficult, especially in Ah-level Zn–I2 pouch cells where polyiodide shuttling accelerates capacity decay and corrodes the nascent anode interface. Here, we integrate machine-learning-guided polyiodide regulation with dynamic interfacial reconstruction to establish a self-activating Zn deposition pathway for reversible anode-free Zn–I2 cells. DFT-supervised screening reveals multidentate weak O–C–H···I interactions and chain-assisted confinement as key molecular design principles for polyiodide confinement, guiding the selection of polyethylene glycol 4000 (PE4000). More importantly, PE4000 gates trace reversible Sn/Sn2+ interfacial conversion, enabling dynamic Zn–Sn reconstruction, persistent zincophilic sites, and orientation-regulated Zn nucleation/growth during repeated plating/stripping. Consequently, the optimized anode-free Zn–I2 cells sustain 16,000 cycles at 10 mA cm–2. Single-layer pouch cells operate for over 3000 cycles at 4.65 mAh cm–2, with recovered Sn remaining reusable for another 1000 cycles. Ah-level pouch cells further deliver 2390 Ah cumulative capacity over 2800 cycles. This work establishes a system-level interface-matching strategy for practical high-utilization anode-free batteries.
Abstract Chemical modification at the C2′ position of nucleosides is critical to nucleic acid therapeutic development, yet general and stereoselective methods for C2′-alkylation remain limited due to synthetic challenges associated with nucleoside substrates. Herein, we report an electrochemical Ni-catalyzed stereoselective C(sp3)–C(sp3) cross-coupling strategy for efficient C2′-α-alkylation of nucleosides. Readily accessible C2′-bromonucleosides and NHPI esters derived from abundant carboxylic acids serve as coupling partners under mild electrochemical conditions, enabling modular installation of diverse alkyl groups with broad functional-group tolerance and excellent diastereoselectivity. The protocol accommodates multiple nucleobases, is scalable, and provides products directly compatible with oligonucleotide synthesis. Biophysical studies indicate that these modifications can modulate DNA/RNA duplex thermal stability and improve resistance to exonuclease degradation. This electrochemical cross-coupling strategy provides an approach to C2′-alkyl-modified nucleosides and expands the toolbox for functional nucleic acid design.
Abstract Achieving high CO selectivity in CO2 hydrogenation with non-noble metal catalysts remains challenging. Here, we report a simple and cost-effective in situ synthesis of nickel–zinc carbide (Ni3ZnC) from Ni species supported on ZnO under reaction conditions. A higher amount of Ni3ZnC forms in the calcined NiO/ZnO catalyst compared to the prereduced Ni/ZnO system. Thermodynamic analysis reveals a strong driving force for Ni3ZnC formation via NiO/ZnO coreduction (ΔE ≈ −455 kJ mol–1), which is more exothermic than the metallic Ni pathway due to favorable H2O stoichiometry. Density functional theory calculations show that the carbide phase moderates surface reactivity. CO becomes geometrically trapped and isolated from hydrogen due to site blocking by Zn and C atoms. This combination of weakened adsorption and site confinement suppresses deep hydrogenation, leading to high CO selectivity over methanation. This strategy provides a practical route for designing selective reverse water–gas shift catalysts for tandem reaction pathways to liquid fuel synthesis.
Abstract Photocatalysts most often leverage long-lived triplet excited states to promote valuable reactivity in organic synthesis. Consequently, many potential photosensitizers remain unviable for catalytic applications because of the kinetic constraints of diffusion-controlled intermolecular electron transfer. Supramolecular mechanisms can obviate this constraint through ground-state association with a reactant, enabling species with short-lived excited-state lifetimes to engage in synthetically relevant transformations. Thus far, the instability of host architectures toward open-shell intermediates has limited their use as photoredox catalysts. Through the synthesis of an oxidatively robust GeIV catecholate cage (Ep/2 = 0.357 V vs Fc/Fc+), we have enabled the (4 + 2) synthesis of isoquinolones via singlet photoredox catalysis. These results establish supramolecular preorganization as a generalizable platform for harnessing the unique redox potentials of singlet excited states in organic synthesis.
Abstract Electrochemical CO2 reduction reaction (CO2RR) in acidic media is attractive for mitigating carbonate formation, yet it typically relies on alkali metal cations to promote CO2RR over the competing hydrogen evolution reaction. Here we show that CH3NH3+, an alkylammonium cation with proton-donating capability, markedly enhances acidic CO2 electrolysis on immobilized cobalt phthalocyanine (CoPc), outperforming alkali metal cations. Compared with Na+, CH3NH3+ increases the CO partial current density by ∼10-fold at modest overpotentials while maintaining ∼95% Faradaic efficiency for CO production. Combined electrochemical analyses and grand-canonical density functional theory calculations reveal a distinct cation role beyond electrostatic stabilization of *CO2: CH3NH3+ serves as an interfacial proton-transfer mediator that enables directed proton transfer to adsorbed *CO2, thereby facilitating the rate-limiting protonation step. This cation-mediated mechanism enables CO partial current densities up to 600 mA cm–2 and single-pass CO2-to-CO conversion approaching 90% in acidic media. These findings expand the conventional view of electrolyte cations in CO2RR and establish cation-enabled interfacial proton transfer as a strategy for promoting protonation-limited electrocatalysis.
Abstract Aqueous battery research has long focused on ionic behavior during reactions but has largely neglected the essential role of reactive water, hindering the mechanistic understanding and limiting breakthroughs in battery performance. Herein, we establish an H2O-engaged perspective in aqueous electrochemistry and identify unfavorable interfacial water orientation as the fundamental degradation mechanism for H2O-engaged redox. In situ spectroscopy, synchrotron radiation analyses, and theoretical simulations demonstrate that N vacancies in the constructed WN artificial interface elevate the work function and positively shift the point of zero charge, thereby inducing interfacial water into an H-down configuration. The energy barrier for the O–H bond cleavage and proton release can be lowered, boosting H2O-engaged Mn2+ oxidation reaction (MnOR) and facilitating uniform planar MnO2 deposition. As a result, the developed Zn–MnO2 aqueous batteries enable a high capacity of 20 mAh cm–2 with 666.7 mAh cm–3, an ultrahigh rate capability of 160 C, and a cycling lifespan over 10,000 cycles. These findings establish interfacial water orientation as a pivotal reaction coordinate for H2O-engaged redox electrochemistry and provide a general mechanism-guided strategy for designing next-generation robust aqueous batteries.
Abstract Precisely positioning two distinct metal centers within covalent organic frameworks (COFs) is inherently difficult because competitive coordination and uncontrolled metal distribution often compromise structural integrity. Herein, we report a rational strategy that overcomes this challenge, enabling the atomically precise construction of a heterobimetallic COF incorporating nickel porphyrin and iron quinoline units. This synthesis leverages fundamental differences in the thermodynamic and kinetic behaviors of metal ions and organic building blocks and achieves near-quantitative metal occupancy at predetermined coordination sites while preserving framework crystallinity. Despite coordinating independently, the two metal centers engage in strong electronic coupling through local orbital hybridization, establishing an efficient charge-transfer pathway that promotes directional electron migration and suppresses recombination. This bimetallic architecture drives efficient defluorination photocatalysis with broad substrate tolerance and robust recyclability, achieving performance inaccessible to any photocatalysts reported to date. Our work provides a generalizable platform for designing heterobimetallic COFs with tailored charge-transfer kinetics for complex organic transformations.
Abstract Alloys are promising anode candidates for all-solid-state batteries (ASSBs) due to their high specific capacities and regulated interphase with the nonflowing solid-state electrolytes (SSEs). However, selection of alloys is constrained by low initial Coulombic efficiency (ICE), which often excludes candidates with high specific capacity and mechanical deformability─parameters essential for high energy density and low-stack pressure operation. In this work, we reassess and unlock the potential of tin (Sn) anodes in ASSBs. By incorporating bismuth (Bi) as a secondary element, we developed low-cost, diffusion-engineered Sn–Bi binary elemental anodes achieving a high ICE (∼90%) and specific capacity (∼700 mAh g–1). Electrochemical characterizations, first-principles calculations, and cross-sectional morphologies reveal that Li3Bi exhibits a significantly higher Li diffusion coefficient (3.5 × 10–6 cm2 s–1) compared to LiSn and Li13Sn5 (1.5 × 10–14 and 1.3 × 10–11 cm2 s–1, respectively), remains stable in a larger voltage window, and facilitates diffusion throughout the electrode for reversible Sn (de)lithiation. Sn–Bi full cells coupled with a LiNi0.82Co0.11Mn0.07O2 (NCM82) cathode demonstrate high rate capability (1 C) and stable cycling with areal capacities up to 10 mAh cm–2 at 23 °C. Multidimensional engineering strategies, from grain to matrix and interface, are further investigated to improve low-stack pressure (5 MPa) performance. This work advances the potential of alloy anodes for practical application of ASSBs.
Abstract Developing efficient and stable oxygen evolution reaction (OER) catalysts under acidic conditions for proton exchange membrane water electrolyzers (PEMWE) is still a pivotal challenge owing to the trade-off between activity and stability. Herein, we synthesize a Cr/Ir dual-atom-doped Cr0.2Ir0.1Ru0.7O2 electrocatalyst, which not only presents a low overpotential of 202 mV but also achieves a long-term stability over 1100 h at 10 mA cm–2 in acidic OER. Importantly, the PEMWE device assembled by using Cr0.2Ir0.1Ru0.7O2 as the anode can operate stably over 1300 h at 0.3 A cm–2. Combining operando spectroscopies (Raman, ATR-SEIRAS, and DEMS) and density functional theory, we find that the Cr and Ir dual-atom incorporation efficiently regulates the electronic structure of Ru and enhances the intrinsic activity of Ru sites, while Ir doping shortens the Ru–O bonds to stabilize lattice oxygen, effectively suppressing the lattice-oxygen-mediated mechanism (LOM) and predominantly following the adsorbate evolution mechanism (AEM). This predominant AEM pathway, together with the downshifted d-band center of Ru and optimized *OOH binding, breaks the conventional activity–stability trade-off of the OER electrocatalysts. In short, Cr/Ir dual-atom doping provides a useful synergistic complementary strategy for high-performance PEMWE anode catalysts.
Abstract Cation effects are central to electrocatalytic CO2 reduction, but freely dissolved cations lack positional control, defined function and persistent coupling to surface motifs. Precise regulation of such ionic microenvironments remains difficult in ligand-stabilized metal nanocatalysts, where interfacial modification often perturbs ligand organization and metal core structure. Here we use atomically precise [Au25(EBA)18]− nanoclusters (EBA = 4-ethynylbenzoic acid) as model electrocatalysts to develop a ligand-recognition strategy for constructing interfacial ionic layers. Phenylbiguanide (PGd) was selected as a bifunctional cation: its phenyl motif enables recognition-driven association with the aromatic EBA ligand shell through CH−π interactions, whereas its biguanidinium unit offers NH2 and NH sites for CO2 binding and activation. This design positions PGd beyond the first ligand shell as a site-proximal ionic promoter, forming a defined ionic layer while preserving access to active sites. Constrained ab initio molecular dynamics calculations indicate that protonated PGd maintains hydrogen-bond coupling with CO2, facilitating CO2 capture and activation near Au sites. Molecular analyses resolve PGd association, binding range and interfacial configuration. Optimized PGd incorporation lowers the overpotential by 200 mV and achieves a FECO of 95.6% at −0.7 V during CO2 reduction. These results establish ligand recognition as a route for converting diffuse cation effects into defined ionic microenvironments on atomically precise electrocatalysts.
Abstract Mitochondrial inner-membrane ultrastructure plays a central role in cellular metabolism, aging, and cell death. However, super-resolution imaging of mitochondria after fixation remains challenging: commercially available fixable probes often lack sufficient reactivity for strong retention during fixation, whereas state-of-the-art probe PKMO FX, despite high fixation efficiency, suffers from low cellular permeability due to the introduction of highly hydrophilic groups. Here, we overcome this “permeability-fixability trade-off” by introducing a rational design strategy centered on amide-to-ester substitution. We report mitochondrial probes, PK Mito 590 FIX and PK Mito 647 FIX, which leverage optimized lipophilic ester linkages to achieve rapid mitochondrial labeling kinetics (labeling within 10 min) and superior aldehyde cross-linking efficiency (>90% signal retention). This molecular engineering enables a seamless transition from live-cell dynamics to post-fixation super-resolution microscopy with unprecedented signal-to-background ratios. Crucially, the enhanced permeability of these probes unlocks post-fixation imaging of multicellular samples, allowing the visualization of mitochondrial architectures within patient-derived cell clusters and isolated mouse islets. Furthermore, we demonstrate that these probes withstand the harsh polymerization conditions of expansion microscopy (ExM), democratizing mitochondrial ultrastructural imaging via standard confocal platforms. Collectively, this toolkit bridges the gap between physiological dynamics and structural definition, offering a versatile platform for multiscale interrogation of mitochondrial biology in both adherent cells and complex multicellular systems.
Abstract The kinetically sluggish sulfur reduction reaction (SRR) governs the performance of ultrahigh-capacity aluminum–sulfur batteries, while deciphering the SRR process is critical for rationally electrocatalyzing reaction kinetics to unlock their full energy output. To overcome this challenge, a single-particle electrochemical methodology has been developed to investigate the SRR process on a cobalt/nickel and nitrogen codoped graphene (CoNi-NG) electrocatalyst. The SRR process involves a major route of S8 → Al2S8 → Al2S4 → Al2S3 with a minor route of Al2S8 → Al2S6 → Al2S4, where Al2S4 conversion governs the overall SRR kinetics and Al2S4 contributes the most to the shuttle effect owing to its fastest generation and slowest consumption. The CoNi-NG raises the Co d-orbital energy level via Ni-to-Co electron transfer to accelerate cleavage of polysulfides, which doubles the exchange current density of rate-determining Al2S4 conversion. Consequently, the sulfur composite (S@CoNi-NG) electrode delivers a specific capacity of ∼1480 mAh gsulfur–1. Such a single-particle methodology for quantitatively deciphering electrocatalytic SRRs offers mechanistic guidance for rationally enhancing battery performance.
Abstract Open-shell nanographenes, featuring highly tunable and correlated magnetic states, constitute a promising platform for engineering graphene nanomagnets towards molecular-scale spintronics and quantum information technologies. However, their magnetic states are largely dictated by topological constraints and strong electronic correlations, limiting independent control of spin and charge degrees of freedom. Here, we introduce a structural dual-site engineering strategy that integrates intrinsic spin modulation with adsorption- and field-controlled charge state tuning in a single magnetic nanographene, enabling a level of multifunctional control not previously demonstrated. We design and synthesize nitrogen, sulfur-co-engineered [3]triangulene (N,S-Tri), incorporating a central nitrogen dopant and an edge sulfur substitution with complementary functions. The central nitrogen modifies the occupation of the frontier π states and thereby tunes the molecular spin configuration, while the edge sulfur site weakly participates in the low-energy π-state and simultaneously acts as a tunable chemical anchor that regulates molecule–substrate coupling and charge transfer. Using low-temperature scanning probe microscopy, we directly visualize switching from neutral to cationic states, driven by adsorption-site variation on Au(111), or reversible switching by local electrostatic gating. This dual-functional design moves beyond static doping or interface charge transfer in graphene nanomagnets, enabling field-controlled dynamic modulation of spin and charge states, and opening new opportunities for device-oriented applications where molecule–electrode interactions and electrostatic field control play central roles.
Intermetallic compounds and multicomponent refractory alloys exhibit numerous applications in catalysis, magnetism, and energy conversion, yet their synthesis remains challenging due to the refractory nature of their constituent elements and inherently sluggish nature of solid-state diffusion that requires extreme reaction temperatures. Herein, we introduce a general CsCl-mediated molten-salt synthetic method that enables single-step, moderate-temperature (<1050 °C) access to finely dispersed single-phase polycrystalline metallic materials across diverse structural families. Binary alloys with melting temperatures over 2000 °C, Laves-type intermetallics, the incongruently melting complex intermetallics such as μ-phase Fe7Mo6, and multimetallic high-entropy alloys (HEAs) were successfully prepared by this facile method. For Fe7Mo6, the synthesis enabled further characterization of magnetic and electrocatalytic properties. The CsCl flux mediates a dissolution-reprecipitation pathway that yields homogeneous polycrystalline powders with controlled stoichiometry. Such alloys and intermetallics can be further converted to corresponding multimetallic MXides, while preserving metal stoichiometry, as demonstrated for phosphides, carbides, borides, and sulfides. Overall, this work establishes a robust and scalable synthetic platform for the facile synthesis of compositionally and structurally diverse refractory multimetallic systems.
Abstract The two-electron/two-proton reduction of O2 to H2O2 has attracted considerable attention recently, as H2O2 is both a valuable oxidant and a potential fuel for H2O2 fuel cells. While metalloporphyrins have been extensively studied as efficient catalysts for this reaction, nonheme metal complexes remain largely underexplored and key catalytic intermediates and rate-determining steps have rarely been identified. Herein, we report the isolation, along with the structural and spectroscopic characterization, of a nonheme μ-1,2-peroxo dicobalt(III) complex, [Co2(μ-1,2-O2)(L)2]2+ (HL = 2-[benzyl[bis(pyridin-2-yl)methyl]amino]-N-(quinolin-8-yl)acetamide), which serves as a key intermediate in the selective two-electron/two-proton catalytic reduction of O2. In the presence of trifluoroacetic acid in acetonitrile at 298 K, ferrocene derivatives act as electron donors to produce H2O2 with 100(2)% selectivity; the generated H2O2 is stable for up to 3 h under the catalytic conditions. The catalytic cycle has been elucidated through an analysis of both overall kinetics and the kinetics of individual steps. The rate-determining step in the catalytic cycle is the electron transfer from 1,1′-dimethylferrocene (Me2Fc) to the mononuclear Co(III) complex, [CoIII(L)]2+, generating 1,1′-dimethylferrocenium ion (Me2Fc+) and [CoII(L)]+. The resulting Co(II) species reacts with O2 to form [CoIII2(μ-1,2-O2)(L)2]2+, which upon protonation yields H2O2 and regenerates two equivalents of [CoIII(L)]2+. This study establishes a new catalytic pathway via the μ-1,2-peroxo dicobalt(III) complex for the selective reduction of O2 to H2O2 using a nonheme metal complex with perfect selectivity. Furthermore, the one-electron oxidation of the μ-1,2-peroxo dicobalt(III) complex affords the corresponding μ-1,2-superoxo dicobalt(III) complex, which was characterized by EPR, CSI-MS, and resonance Raman spectroscopies.
Abstract Particulate Z-scheme overall water splitting holds considerable promise for solar hydrogen production, yet its potential is persistently constrained by mediator-involved reverse reactions and related interfacial charge loss. Here we show that water-splitting reactions and parasitic mediator redox can be spatially decoupled across microscale surface domains, thereby suppressing reverse chemistry at its origin. Using facet-engineered Y2Ti2O5S2 and BiVO4 microcrystals as H2-evolving and O2-evolving photocatalysts, respectively, anisotropic charge separation together with facet-selective mediator adsorption directs mediator redox to specific facets, while H2 and O2 evolution proceed on the lateral facets of both photocatalysts. This spatially organized interfacial architecture separates forward and parasitic pathways within individual particles, suppressing mediator self-cycling and H2/O2 recombination without hindering productive interparticle charge transfer. Consequently, visible-light-driven overall water splitting activity is enhanced by over 60-fold relative to the nonfaceted counterpart, delivering an apparent quantum yield of 17.1% at 420 nm, a solar-to-hydrogen efficiency exceeding 1.0%, and sustained activity near atmospheric pressure. These findings establish spatial decoupling of interfacial redox sites as a general design principle for mitigating reverse reactions in Z-scheme artificial photosynthesis for solar hydrogen production.
Abstract 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) is a widely used bifunctional organocatalyst; however, its microscopic behavior in hydrogen-bonding environments remains poorly understood. In this study, we employed broadband rotational spectroscopy to identify the stepwise microhydration of TBD with one to four water molecules, and investigated how solvent molecules progressively alter its structure and electronic properties. We found that the bifunctional character and rigid bicyclic skeleton of TBD govern the growth of the hydrogen-bond network, while simultaneously inducing significant geometric distortion in the TBD skeleton. Notably, the formation of double hydrogen bonds induces pronounced ring twisting and drives an electronic structural transition from a “π-localized” to a “π-delocalized” state. The water-induced electronic structure rearrangement is supported by experimental nuclear quadrupole coupling constants and theoretical natural population analysis. These results demonstrate that the basicity and reactivity of TBD are not inherent constants, but can be dynamically modulated by local hydrogen-bonding networks, offering new insights for the design of more efficient hydrogen-bond-assisted catalytic systems.
Abstract Sialic acid (Neu5Ac) is a monosaccharide terminating glycoconjugates, serving as ligands for lectins in health and disease. Tools to target sialyltransferases (STs) and neuraminidases (NEUs) are important in the study of sialoglycans. 3FaxNeu5Ac is a common ST inhibitor, while 2,3diFNeu5Ac is a covalent mechanism-based NEU inactivator. Here, we demonstrate the advantages of having two fluorines at C3 for both classes of inhibitors. Motivated by the finding that 3FaxNeu5Ac is transferred by STs slowly, we aimed to synthesize 3,3-difluoro-Neu5Ac (3,3diFNeu5Ac). Two fluorines at C3 successfully prevented ST-mediated transfer. Unexpectedly, CMP-3,3diFNeu5Ac is 5–40-fold more potent than CMP-3FaxNeu5Ac against five human STs. Moreover, CMP-3,3diFNeu5Ac was 6–11-fold more potent toward ST3GAL1 than the four STs tested. While protected 3,3diFNeu5Ac was not very active in cells, CMP-3,3diFNeu5Ac was surprisingly active, showing enhanced inhibition toward ST3GAL1 over ST6GAL1, translating to selective inhibition of Siglec-7 ligands over Siglec-2 ligands. To target NEUs, 2,3,3-trifluoro-Neu5Ac (2,3,3triFNeu5Ac) was synthesized as a mechanism-based covalent NEU inhibitor. For 2,3diFNeu5Ac, a covalent glycosyl-enzyme intermediate was formed that broke down, but covalent inhibition of bacterial and viral NEUs by 2,3,3triFNeu5Ac was more stable. Therefore, through synthetic access to 3,3diFNeu5Ac, more potent and stable inhibitors of STs and NEUs were developed, which can serve as better tools to probe the functions of sialoglycans.
