Chemically induced proximity of biomacromolecules is a powerful strategy to regulate cellular processes using small molecule ligands that act as “molecular glues” to influence complex lifetime, localization and function. However,...
Macrocyclic peptides possess numerous advantages, including enhanced tissue penetration, low immunogenicity, good resistance to protease degradation, and high targeting specificity, making them increasingly attractive for drug development. Genetically encoded cyclic...
The practical application of aqueous zinc-ion batteries (AZIBs) is severely hindered by the poor reversibility of Zn anode, which stems from a self-amplifying cycle involving dendrite growth, interfacial side reactions,...
The protection of N ̶ H groups is often essential to harness highly valuable metal-catalyzed C ̶ C coupling protocols. However, the avoidance of protecting groups has enormous advantages in...
The complex absorbing potential (CAP) method is an effective approach to model anionic resonances. However, the existing optimization criteria for the CAP strength give rise to multiple solutions, and the...
Redox imbalance is closely associated with atherosclerosis (AS), but tools for precise, simultaneous, and in situ imaging of oxidative NO and reductive H2S within the AS plaque microenvironment are still lacking. Herein, we developed a bioorthogonal small-molecule fluorescent probe, DBCO-BOD-NH, for dual-channel imaging of NO and H2S. The probe is built on a BODIPY fluorophore, incorporates a dibenzocyclooctyne (DBCO) bioorthogonal group, and combines metabolic labeling with an unnatural sugar (N3-AC4GlcN). Through a "recognition-reporting" separation strategy, it achieves high signal-to-noise, synchronous imaging of both gasotransmitters in the plaque microenvironment. In vitro, the probe exhibits excellent optical properties, high selectivity, and good photostability. Cellular imaging reveals a dynamic inverse evolution during macrophage-to-foam cell transformation: NO levels gradually increase while H2S levels decrease. In animal models of AS and diabetes-combined AS, plaque progression is accompanied by increased NO and decreased H2S levels, and diabetes further exacerbates the NO-H2S redox homeostasis imbalance. This study not only provides a dual-channel imaging tool to investigate the dynamic evolution of NO-H2S imbalance in the AS plaque microenvironment, but also offers reliable evidence for the direct involvement of gasotransmitters in diabetes-accelerated AS progression.
Compared with 3d transition metals, rare-earth elements, particularly cerium, exhibit more markedly sluggish Fenton-like reaction kinetics, making them more stable under oxidative oxygen reduction reaction (ORR) conditions. Here, a dual-atom cerium catalyst is fabricated on nitrogen-doped graphene (Ce2-NG) through an ultrafast Joule-heating strategy. This rapid synthesis enables the construction of Ce-Ce dimers within milliseconds, effectively suppressing aggregation and ensuring the atomic-level stabilization. Ce2-NG demonstrates remarkable ORR performance, reaching a half-wave potential of 0.906 V, along with superior durability and strong resistance to methanol crossover. When employed as the cathode catalyst in a zinc-air battery (ZAB), the device exhibits an elevated open-circuit voltage and excellent long-term operational stability, clearly surpassing those of Pt/C + RuO2 counterparts. Operando spectroscopy combined with density functional theory supports the Ce2-N6 moiety as the active center, where dual-atom cerium cooperation drives charge redistribution, enhances *OH binding, and lowers the free energy change of the potential-determining step. This study introduces a controllable synthesis method for constructing rare-earth dual-atom catalysts, broadening the compositional landscape of atomically dispersed electrocatalysts for sustainable energy conversion.
Solar-driven photocatalytic H2O2 synthesis is critically hampered by bulk charge recombination and spin-forbidden surface kinetics. This study proposes a rare-earth 4f-state-mediated strategy that simultaneously reconstructs the band structure and induces spin polarization. Using Aurivillius-phase Bi3TiNbO9 as a ferroelectric model system, we show that low-concentration Ce doping engenders three synergistic effects via a full-pathway charge-dynamics regulation: (i) Ce-induced lattice distortion enhances ferroelectric polarization, reinforcing the polarization electric field for directional charge separation; (ii) band-edge reconstruction reduces both carrier effective masses and exciton binding energy, accelerating exciton dissociation and carrier transport; and (iii) the unpaired 4f1 electron of Ce3+ induces spin polarization, effectively lowering the spin-related kinetic barriers for H2O2 generation. Consequently, Ce-doped Bi3TiNbO9 delivers an H2O2 production rate of 1151.7 µmol g-1 h-1 in pure water, a 6.9-fold enhancement over pristine Bi3TiNbO9. Critically, applying a 300 mT external magnetic field further boosts the rate to 1831.2 µmol g-1 h-1, providing direct evidence for spin-polarization-controlled photocatalysis. H2O2 is selectively generated through synergistic 2e- oxygen reduction reaction (ORR) and water oxidation reaction (WOR) pathways, while the competing side reactions are effectively suppressed. This work demonstrates an integrated 4f-mediated charge-spin regulation strategy that couples charge separation with spin-dependent surface reaction kinetics for efficient H2O2 photosynthesis.
Functionalized nanographenes are emerging near-infrared emitters, yet the microscopic pathways underlying their ultrafast excited-state dynamics remain elusive. Here, we combine atomistic nonadiabatic simulations with transient absorption (TA) modeling to analyze the relaxation mechanisms in a donor-acceptor nanographene. We find that, during the decay of the initially populated higher-lying excited states, the transition density redistributes from the substituents to the nanographene core. This early process occurs in both fully flexible and dihedral-constrained trajectories. In contrast, relaxation into the lowest excited state is strongly torsion-dependent: freezing the donor-acceptor dihedral suppresses this nonadiabatic decay and traps population in higher-lying excited states. Decomposition of the TA signal into ground-state bleaching, stimulated emission, and excited-state absorption elucidates that access to the lowest excited state correlates with the buildup of stimulated emission in the near-infrared, while excited-state absorption remains weak in this spectral window. These results disentangle early electronic relaxation from torsion-assisted interstate decay and clarify how structural dynamics shape the spectroscopic signatures associated with efficient near-infrared emission in functionalized nanographenes. These insights provide molecular-level design principles for controlling excited-state relaxation and enhancing optical gain in near-infrared emitters.
Co-assembly and self-sorting in multicomponent systems are typically treated as mutually exclusive outcomes. Here, we show that this distinction is incomplete. Using enantiomeric peptide nanotubes, we demonstrate that a single co-assembled structure forms only at an equimolar composition, yet remains internally self-sorted into compositionally distinct domains. Contrast-matched neutron scattering directly reveals this segregation and shows that the co-assembled structures adopt layered architectures rather than simple molecular-level mixing. These results establish that co-assembly and self-sorting can coexist within a single supramolecular object across length scales, providing a general framework for understanding and controlling multicomponent self-assembly.
The limited redox chemistry of rare-earth (RE) elements means that multi-electron transfer reactions with RE compounds are a major synthetic challenge. Here, we demonstrate multi-electron reduction of a borole in two complementary RE reaction systems. In the first approach, the dimetallic lanthanum(iii) compound [(η 5-C5 i Pr5)La(µ:η 6:η 6-C6H6)La(η 5-C5 i Pr5)], containing a benzene tetra-anion ligand, reduces two equivalents of the ferrocenyl-borole FcBC2(SiMe3)2C2Me2 (1) to give the double sandwich complex [{(C5 i Pr5)RE}FcBC2(SiMe3)2C2Me2] (3-RE, RE = La), containing a 6π-aromatic borolide di-anion. In the second, complementary reaction type, combining KC8 with 1 and the half-sandwich complexes [(C5 i Pr5)RE(BH4)2(THF)] (RE = Y, La, Dy) also gives 3-RE but with a broader range of rare-earth elements. In 3-RE, evidence for two-electron reduction of the borole is supported by comparisons with the magnesium borolide [Mg(FcBC2(SiMe3)2C2Me2)(THF)3] (2). In contrast, salt-metathesis approaches to 3-RE were ineffective, with alkali metal reduction of the borole proving to be unsuccessful, and 2 does not undergo salt metathesis with rare-earth precursors. The dysprosium analogue 3-Dy exhibits single-molecule magnet behaviour, with an effective barrier of 1222(8) cm-1 and magnetic hysteresis up to 60 K.
The strain-release reactivity of azabicyclo[1.1.0]butanes (ABBs) offers a powerful entry to substituted azetidines, yet modular access to highly functionalized, allylic amine-containing frameworks remains underdeveloped. Here, we report a visible-light copper-catalyzed four-component coupling that effects 1,4-carboamination of aryl-substituted 1,3-dienes, assembling azetidines bearing a quaternary carbon center from dienes, aryl amines, and electrophiles using ABBs. Synergistic copper/photoredox catalysis unites strain-release generation of an azetidinyl radical with allylic C-N bond formation, delivering densely functionalized azetidines bearing an allylic amine in a single, redox-neutral operation. The reaction proceeds with high 1,4-regioselectivity and broad functional-group tolerance across diverse anilines, ABBs, dienes, and electrophiles, and operates under mild conditions. Biorelevant complex-molecule diversification, scalability, and downstream derivatization underscore the synthetic utility of the platform, while DFT calculations trace the 1,4-selectivity to stabilizing noncovalent interactions that favor benzylic C-N coupling and steric repulsion that disfavors the competing pathway.
The metal complexation of π-electronic systems with partial charge compensation for metal ions produces positively charged π-electronic systems that can act as building blocks for ion-pairing assemblies. In this study, the CuII complexation of thiaporphyrins was investigated to afford paramagnetic π-electronic cations that modulate ion-pairing assembly modes in combination with coexisting anions. Counteranion-dependent stacking modes regulated spin-spin interactions between the CuII complex cations, resulting in antiferromagnetic properties in the solid state.
Photoreduction of CO2 and H2O into CH4 offers a sustainable pathway for solar-to-chemical energy conversion. However, premature desorption of the CO* intermediate before coupling with protons (H*) to form CHO*...
Coking and decoking chemistry remains a long-standing yet critical issue in zeolite catalysis. A steam-induced decoking strategy offers a promising regeneration route that converts polycyclic aromatic hydrocarbons (PAHs) into valuable intermediates or products, but the dynamic evolution of coke and the underlying mechanism remain ambiguous. Here, we found that high-temperature steam treatment of coked SAPO-34 catalysts not only fully restores methanol conversion activity but also remarkably enhances ethene selectivity. To understand the origin of this regeneration and selectivity improvement, we traced the involvement trajectory of H2 18O and captured previously unrecognized oxygenated intermediates by integrating 18O isotopic labeling with GC-MS. The hydroxylated species are primary products from the steam scission of cross-linked macromolecular coke, whereas the phenalenone species is proposed to participate in the transformation of polycyclic pyrene to naphthalene-derived species, which work as hydrocarbon pool species and favor the enhancement of ethene selectivity. DFT calculations further clarified a reasonable evolution pathway encompassing these oxygenated intermediates and hierarchical aromatic species, which outlines a stepwise deep cracking trajectory of PAHs. This work thus elucidates the transformation of polycyclic aromatics to active species during steam regeneration, and deepens fundamental insights into zeolite decoking chemistry as well as rational regulation of catalytic performance.
Conformational plasticity offers a powerful route to adaptive molecular materials, yet its translation into guest-dependent superstructures with controllable function remains rare in the case of synthetic macrocycles. Here we show that two conformationally adaptive macrocycles, MeC3 and MeC4, provide a well-defined macrocyclic platform for investigating guest-dependent conformational plasticity in the solid-state. Specifically, supramolecular co-assembly of MeC3 with molecular guests that differ in geometry, polarity and electronic character affords a diverse set of guest-dependent macrocyclic polymorphs and higher-order solid-state host-guest superstructures. Combined spectroscopic, computational, and crystallographic analyses correlate guest identity with the stabilization of distinct macrocyclic conformations that then propagate into divergent packing modes and superstructures. As a presumed consequence of the adaptive solid-state behavior, MeC3 crystals selectively sieve benzene vapor from benzene/cyclohexane mixtures with >95% selectivity. The MeC3 sieve material can be readily regenerated through a reversible guest-loaded to guest-free crystal-to-crystal transformation. In contrast to MeC3, MeC4 proved effective as a solid-state receptor for fullerenes C60 and C70. This work highlights solid-state conformational plasticity as a promising design principle for the creation of functional solids with emergent recognition, assembly, and separation properties.
Small-molecule drug discovery is increasingly applied to targets historically classified as "undruggable", such as non-coding RNAs and biomolecular interactions. These complex interfaces demand ligands with greater three-dimensional complexity and preferred physicochemical profiles that are deficient in typical small molecule chemical libraries housed in large pharmaceutical companies or commercial suppliers. Inspired by the need for novel libraries that might hypothetically address these target classes, we report the design, iterative synthesis, and comprehensive property profiling of a novel chemical library of shape-defined, morpholine-containing pentacycles. Utilizing iterative Stannyl Amine Protocol (iSnAP) reagents, we divergently assembled rigid, 3D-diverse scaffolds that exhibit a chameleonic basic character at physiological pH, elegantly balancing aqueous solubility with membrane permeability. Computational analysis of the 2400-member virtual library confirmed that it occupies a distinct, three-dimensional chemical space. Furthermore, high-throughput experimental profiling of the synthesized compounds revealed promising drug-like properties, including broad aqueous solubility, metabolic stability, low cytochrome P450 inhibition, and tunable membrane permeability. Although no bioactivity has yet been discovered from this library, the compounds offer a robust chemical foundation for future evaluations in ligand screenings targeting emerging therapeutic modalities.
Efficient drug discovery workflows ideally generate data that directly address key translational milestones, including confirmation of target engagement and binding pose, structure-activity relationships (SAR), and biological relevance, within rapid and...
Classically defined oxidation numbers (in addition to quantum-chemical population analyses) are regularly used to quantify or at least stick to the ionic notion of molecules and solid-state materials. As such,...
Structure-sensitive properties (SSPs), including activity cliffs and chirality-dependent properties, challenge molecular machine learning because small structural perturbations can cause abrupt property changes and invalidate smooth structure-property assumptions. Here, we present...
