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Smart probes are crucial for precise theranostics. The current focus of most research in precise theranostics has mainly centered on the activation process of smart probes after intravenous injection into target tissues. However, subsequent events following the probe activation within target tissues are typically overlooked. Of particular note is the underexplored aspect of activated probe diffusion from diseased to normal tissues. Herein, we present the latest development on off-on-off probes, highlighting not only their activation upon intravenous injection into target tissues but also the subsequent diffusion of activated probes from target to normal tissues. In particular, we focus on molecular design strategies to achieve off-on-off signal control, including approaches such as intramolecular donor-acceptor reconfiguration, assembly, disassembly, Förster resonance energy transfer, molecular structure tautomeric forms, dynamic steric effects, biodegradation, and multimechanism combination. We provide a comprehensive summary of how these probes have been evaluated in preclinical models, focusing on their advantages over conventional off-on probes in enhancing imaging specificity and reducing off-target therapeutic side effects. Finally, we offer forward-looking insights into the advancement of off-on-off theranostic probes, their broader integration into biomedical applications, and the challenges that must be addressed for practical implementation.

Single-atom catalysts (SACs) have shown exceptional promise in a variety of selective hydrogenations due to their uniform and isolated active sites, yet the intrinsic nature of the active sites and reaction mechanism remain elusive. Herein, by a rapid thermal treatment (RTT) method, we are able to finely tune the coordination structure of Pt1/CeO2 SAC and establish a linear correlation between the Pt-O coordination number, electronic structure, and catalytic activity for furfural/3-nitrostyrene hydrogenations. Integrated quasi in situ spectroscopic characterizations and DFT calculations reveal the structural evolution of Pt1-Ov-Ce active sites and the redox mechanism. RTT at 600 °C results in the formation of Pt1-Ov-Ce, which allows for the preferential end-on adsorption of ─C═O/-NO2 groups into Ov and the charge transfer from the Pt1 single atom to the reactant. On the other hand, hydrogen is dissociated on the Pt single atoms and then reacts with the adsorbed ─C═O/-NO2 group to accomplish the selective hydrogenation, accompanied by the regeneration of Ov. Moreover, the interfacial Pt1-Ov-Ce is found to be 2.4-15.7-fold more active than Pt1---Ov (peripheral Ov). These findings highlight the dictating role of the coordination structure of SACs and elucidate the cooperative mechanism between Pt single atoms and interfacial oxygen vacancies, thus offering design principles for overcoming the activity-selectivity trade-off in other selective hydrogenations.

The development of the molecular chemistry of lanthanides in the +4 oxidation state has encountered significant challenges due to their limited solution stability. Here, we demonstrate that combining siloxide ligands with oxo ligands leads to highly stable PrIV complexes. We report that the PrIII/PrIII oxo-bridged complex, [K(tol)K4{PrIII(OSiMe3)5}{PrIII(OSiMe3)4}(μ-O)], 4, can be easily prepared by controlled hydrolysis of the pentakis-siloxide complex [K2PrIII(OSiMe3)5]2, 2, followed by deprotonation. Oxidation of complex 4 with thianthrene tetrafluoroborate (thiaBF4) in the presence of KOSiMe3 afforded the PrIII/PrIV mixed valent complex [K(tol)K4{PrIII/IV(OSiMe3)5}2(μ-O)] 5 that showed localized valence with a very short PrIV═O bond, consistent with multiple bonding interactions. DFT studies further confirmed the presence of a polarized PrIV═O multiple bond along with a very weak ionic PrIII-O interaction. Further oxidation of complex 5 led to the isolation of the PrIV/PrIV complex [K4{PrIV(OSiMe3)5}2(μ-O)], 6. Complex 6 shows remarkable solution stability at room temperature over a long period of time. Interestingly, the EPR spectra and magnetic properties of these molecular PrIV complexes closely resemble those of PrIV ions in perovskite oxide lattices. We anticipate the presented strategy will pave the way for the development of new LnIV chemistry.

The structural analysis of the ecto- or cytosolic domains of membrane proteins is frequently realized through the analysis of isolated domains, i.e., by using a divide-and-conquer approach, as membrane protein expression remains a laborious task. However, the membrane environment can influence the structural features of the protein. Here, we investigated the membrane-bound form of the cytosolic zinc finger domain of the Crimean-Congo hemorrhagic fever virus glycoprotein n (GnTMcyto), which had previously been studied in isolation. We obtained the membrane-reconstituted protein by cell-free protein synthesis and analyzed it using 1H-detected solid-state NMR. We show that the overall structure of the zinc finger motif is conserved in GnTMcyto, but interestingly observe that the membrane-bound version has two major conformations, as revealed by peak doubling. This likely indicates that the cytosolic domain forms a multimer in its membrane-bound form, with an at least partially asymmetric conformation. NMR relaxation measurements further reveal that the protein includes dynamic components, providing a possible rationale for the absence of Gncyto in cryo-EM structures of the envelope glycoproteins in other Bunyaviricetes.

Acetylcholine was identified over a century ago with early studies focusing on its release from neuronal systems; while a growing interest in non-neuronal systems has emerged, little is known about acetylcholine release from glioblastoma cells, and its mechanism remains unexplored. Here, we quantified the real-time acetylcholine release from live, single U-87 MG glioblastoma cells and investigated its mechanistic framework through the combination of nanoelectrodes with an interface between two immiscible electrolyte solutions and nano-resolved positioning using scanning electrochemical microscopy. Complementary to conventional solid electrodes, this measuring technique enabled quantitative and selective detection of redox-inactive acetylcholine. We hypothesized that U-87 MG glioblastoma cells may release acetylcholine, considering they express cholinergic markers and exhibited a ∼3-fold increase in intracellular calcium activity following KCl stimulation. We achieved the highly sensitive local measurement of the acetylcholine release by positioning the electrode ∼200 nm away from the glioblastoma cell surface. The release of acetylcholine from U-87 MG glioblastoma cells in the substantially reduced calcium environment or with the treatment of vesamicol, an inhibitor of vesicular acetylcholine transporter, only decreased slightly from the control condition. This suggests the presence of a possible nonvesicular mechanism of acetylcholine release in cancer cells, differing from neurons. The unprecedented findings on the acetylcholine release mechanism in U-87 MG glioblastoma cells presented here provide new insights in understanding the role of acetylcholine in glioblastoma disease progression.

The rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is used globally to retard tire oxidative aging. While its photochemical fate in aqueous systems is known, little is understood about its behavior under freezing conditions across the cryosphere. Here, we show that ice acts as an efficient photochemical medium that converts 6PPD to the toxic 6PPD-quinone (6PPDQ) via a dual-oxygen mechanism involving both O2 and H2O. Mechanistically, the freeze-induced concentration of 6PPD within the liquid-like layer of ice induces J-aggregation of 6PPD, which facilitates intersystem crossing and prolongs the triplet exciton lifetime, thereby enhancing the quantum yield of superoxide radicals from O2. The proton enrichment (i.e., pH decrease) concurrently shifts 6PPD to its 6PPDH22+ form and activates a nucleophilic attack by H2O that is thermodynamically unfavorable in bulk water. These combined effects yield a 3.9-fold higher molar yield of 6PPDQ in ice than in aqueous solution, with the photodegradation products of 6PPD in ice causing substantially increased mortality of E. coli and zebrafish embryos. Our findings thereby uncover a previously unrecognized route and mechanisms of 6PPDQ formation and raise critical concerns regarding the fate and ecological risks of 6PPDQ in seasonally frozen eco-environmental systems.

Innovative molecular solar thermal (MOST) energy storage systems based on the [4 + 4] photodimerization and exothermic thermal retro-cycloaddition of substituted anthracenes have been developed by the Han group. We present new experimental results and comprehensive computational investigations elucidating the mechanisms underlying these MOST systems. Density functional theory (DFT) and spin-flip time-dependent DFT (SF-TDDFT) calculations are employed to examine the photochemical [4 + 4] dimerization and the stepwise diradical thermal retro-cycloaddition responsible for heat release. The onset temperature for retro-cycloaddition is found to relate to the computed activation barrier. A linear relationship between the calculated reaction exothermicity and the experimental activation temperature provides a principle that is useful for the design of anthracene-based MOST energy storage systems. QM/MM calculations on reactions in the crystalline state reveal how crystal forces influence the mechanism and rate of a solid-state retro-cycloaddition. The quantitative relationships among these energetic quantities lead to new designs of promising MOST molecules.

Metal nanoclusters (NCs) with a particle size of approximately 1 nm exhibit potential as highly active catalysts owing to their large specific surface areas and unique electronic structures. However, their precise synthesis in air is predominantly limited to coinage metal (Cu, Ag, and Au) NCs. Consequently, the development of a facile synthesis method for NCs composed of diverse metal elements is highly desirable. Accordingly, we focused on iridium (Ir), which is known for its high catalytic activity in numerous reactions. In this study, we established a precise synthesis method for air-stable Ir NCs and investigated their electrocatalytic activity in the oxygen evolution reaction (OER). We demonstrated that stable Ir∼15 NCs can be synthesized employing carbon monoxide and triphenylphosphine as stabilizing ligands. Furthermore, the OER catalysts derived from these Ir∼15 NCs as precursors exhibited a 1.5-fold increase in OER activity compared with commercially available Ir catalysts. These findings are anticipated to provide valuable design guidelines for the synthesis of NCs and the development of highly active electrocatalysts using a broad range of metal species.

Spin state, a variable factor at the electronic level, plays a significant role in determining the properties of metal complexes. However, the variability of the spin state has largely been regarded as a phenomenon to explain reaction mechanisms rather than as a chemical tool for controlling reaction selectivity. Herein, we report a nickel-catalyzed regiodivergent allylic substitution reaction of vinyl epoxides with styrylboronic acids, where the regiodivergence is directed by switching the spin state of the nickel catalysts. Linear and branched skipped diene alcohols were synthesized with broad substrate compatibility. Additionally, the enantioconvergent synthesis of branched products from racemic vinyl epoxides was achieved through dynamic kinetic asymmetric transformation. Mechanistic investigations confirmed the critical role of coordination modes with varying spin states of the nickel catalysts in achieving regiodivergence.

While birefringence is determined by both the structural units and spatial arrangement within a crystal, the design of the latter remains highly challenging, largely due to the difficulty in controlling microscopic packing. Molecular crystals feature host-guest architectures, which offer an effective means of structural design by enabling the spatial arrangement of the host framework through the guest molecules. Herein, the molecule S8, characterized by its homoatomic bonding and planar-like configuration, exhibits significant polarizability anisotropy; then, by employing a new guest-symmetry modulation strategy, a series of guest molecules, including quasi-spherical SnI4, triangular pyramidal AsI3 and SbI3, and mixed-anion CHI3 that were successfully incorporated into the S8 host lattice, serves as structural directors that switch the S8 arrangement from an offset to a parallel alignment. Such control yields tunable birefringence, from a suppressed 0.182 (SnI4·(S8)2) to enhanced large values of 0.333 (S8), 0.596 (AsI3·(S8)3), 0.641 (SbI3·(S8)3), and finally giant 0.711 (CHI3·(S8)3) @546 nm, the last of which is the largest among known inorganic molecular crystals. The specific directionality of host S8 molecules is achieved via self-assembly, which is driven by the electrostatic potential of the incorporated guest molecules. These results not only validate the effectiveness of the guest-symmetry modulation strategy but also underscore its potential for the design of birefringent materials.

The vitrification of metal-organic frameworks (MOFs) enables melt processing into bulk, shaped and membrane-type porous materials, yet the limited chemical diversity of existing MOF glass formers restricts structural and functional tunability. Here, we demonstrate a general flux-melting strategy in which inorganic zinc halide glass formers (ZnCl2, ZnBr2 or ZnI2) are co-melted with seven zeolitic imidazolate frameworks (ZIFs) spanning different imidazolate-type linkers and network topologies, including both established ZIF glass formers and frameworks that do not melt or vitrify on their own. The zinc halides act as compatible co-network formers and reactive fluxes, promoting extensive ligand exchange between halides and imidazolate linkers in the melt. This process generates mixed halide-imidazolate coordination glass networks whose structure, connectivity and porosity can be tuned systematically through composition. One of the resulting mixed coordination glasses displays substantially enhanced thermodynamic sorption selectivity for propylene over propane compared to its parent ZIF glass. These results establish zinc halide flux melting as a general route to expand the compositional space of MOF glasses and introduce mixed coordination networks as a new design paradigm for functional porous glasses.

Despite the importance of sulfoxides in synthesis and biology, the utilization of sulfinyl radicals for their construction remains underexplored compared to other sulfur-centered radicals. While the Persistent Radical Effect (PRE) offers a powerful framework to harness these stabilized species for radical-radical cross-coupling, the development of general transformations is rare due to the lack of modular sulfinyl radical precursors. Herein, we report N-sulfinyl phthalimides as bench-stable, modular precursors that selectively liberate persistent sulfinyl radicals upon single-electron reduction. This strategy enables the first general 1,2-trifluoromethyl-sulfinylation of unactivated alkenes and robust PRE-guided cross-couplings with diverse alkyl radicals derived from C-H bonds, Hantzsch esters, or carboxylic acids. Furthermore, we report the first generation of unsymmetrical sulfinyl sulfones and elucidate a mechanism driven by their rapid tautomerization, enabling a catalyst-free, ambient-temperature protocol for the direct conversion of sulfinate salts into sulfoxides. The broad utility of these protocols is demonstrated by the successful difunctionalization of ethylene gas and the late-stage modification of complex medicinal compounds, alongside versatile product derivatizations. This work establishes a versatile platform for radical sulfinylation governed by precise kinetic control.

Pyridines are ubiquitous scaffolds in pharmaceutical chemistry and appear in approximately 90% of pyridine-derived drugs as C2-substituted motifs. Nevertheless, direct C-H bond molecular editing remains limited by stringent reaction conditions and low metal atom efficiency. Here, we report the first site-selective aryl-substituted 2-hydroxymethylation at the C2 position of pyridines, enabled by relay mediation between a single-atom zinc-modified cathode and iodide ions. The protocol shows broad substrate tolerance, low metal loading, operational simplicity, negligible overpotential, and high regioselectivity. Direct molecular modification of drugs is achieved, and gram-scale synthesis of Bisacodyl is demonstrated. Mechanistic studies indicate that anodic iodide oxidation suppresses the intrinsic C4 reactivity preference of pyridine radicals. Coupled with a relay sequence comprising adsorption, activation, electroreduction, coupling, and electrooxidation, this effect enables efficient formation of the target products. By integrating single-atom catalysis with relay paired electrolysis, this work provides a new framework for the electrocatalytic transformation of inert chemical bonds.

Harvesting multiexcitons generated by singlet fission (SF) holds promise for advancing optoelectronic devices and photochemistry. Conventional approaches have previously focused on interfacial exciton or charge transfer after dephasing the triplet-pair [T1T1] to low-energy free triplets. However, multiexciton-driven processes that directly leverage the unique characteristic multireference wave function of the [T1T1] state and its high chemical potential are underexplored, opening new opportunities for advancing photochemistry. Here, we report a functional multicomponent system with covalently integrated electron-rich moieties to direct multiexciton charge transfer directly from the [T1T1] state to a charge-separated diradical (CS) state, a previously unreported transformation. We elucidate the design rules of second generation [G2] SF chromophores using spectroscopic studies, including the role of the local dielectric environment in modulating the fate of the triplet pair from conventional triplet pair dephasing to multiexciton charge separation. These findings provide fundamental insights into multiexciton dynamics and lay the foundation for unconventional multiexciton-driven energy conversion systems.

Metal particle-size effects in heterogeneous catalysis are commonly interpreted in geometric terms, where catalytic trends arise from variations in the density of active surface ensembles while the intrinsic properties of the sites are generally assumed to remain unchanged. Here we demonstrate that metal particle size also governs the intrinsic properties of active sites via size-dependent electronic promotion, beyond conventional geometric effects. Using well-defined Ru catalysts supported on multiwalled carbon nanotubes for ammonia synthesis, we separate the geometric contribution of B5-like site density from changes in the intrinsic properties of the sites induced by electronic promotion. Without promoters, the adsorption and catalytic properties of these sites remain essentially invariant with particle size, consistent with classical geometric interpretations. In contrast, with electronic promotion using BaO, interfacial charge storage and capacitive effects enable smaller Ru particles, with higher surface-to-volume ratios, to accumulate greater electron densities. This size-dependent electronic enrichment directly tunes the intrinsic reactivity of individual B5-like sites, strengthening N2 activation through enhanced π-backdonation and alleviating hydrogen poisoning, leading to higher site-specific activity. These findings establish particle size as a dual control parameter that modulates both site density and intrinsic site properties via electronic effects, providing new insight into the complex interplay between catalyst structure, charge distribution, and intrinsic catalytic activity.

The temperature and pressure dependence of the crystal structures and photophysical properties of three crystalline polymorphs of imidoylamidinato Pt(II) complexes exhibiting green luminescence (UG form, main phase), yellow luminescence (UY form), and orange luminescence (UO form) under ambient temperature and pressure were investigated. While the UG and UO forms did not show phase transitions in the temperature range of 300-90 K and below 6.5 GPa (UG) or 3.2 GPa (UO), the UY form exhibited inverse symmetry breaking induced by temperature and pressure. Based on observations of temperature- and pressure-induced phase transition processes using single-crystal X-ray diffraction and optical microscopy, these phase transitions were confirmed to proceed in a single-crystal to single-crystal manner via a twinning deformation process, in which multiple structural domains corresponding to different phases coexisted simultaneously within individual crystal particles during the transformation. It was revealed that, in the UY form, the strength of the interaction between BF4- ions and complex cations changes with temperature and pressure. This triggers a phase transition by inducing alterations in the arrangement of complex cations and counter-anions. In terms of contracting the crystal lattice, the effects of cooling and pressurization are similar. However, observing different luminescence behaviors in the UO and UY forms under temperature and pressure changes revealed that temperature and pressure do not necessarily have consistent effects on the stability of the excited state.

Single crystals of CsTb(CrO4)2 and CsDy(CrO4)2, where the lanthanide metals are in the trivalent state under ambient conditions, have been investigated under high-pressure conditions on the gigapascal scale utilizing a diamond anvil cell. These compounds were characterized by single-crystal X-ray diffraction in addition to high-pressure solid-state UV-vis-NIR spectroscopy, Raman spectroscopy, and Tb L3-edge high-energy-resolution fluorescence-detected X-ray absorption near-edge structure (HERFD-XANES). The high-pressure UV-vis-NIR spectra reveal strong broadening of the metal-to-ligand charge transfer band to lower energies, associated with a visible color change from yellow to dark red/black. Clear evidence for the stabilization of Tb4+ under high pressure is provided by the appearance of a second edge feature characteristic of Tb4+, starting at 19.62 GPa in the high-pressure L3-edge HERFD-XANES at around 7528 eV. This represents the first example of Tb4+ being stabilized by high pressure and expands upon the limited chemistry of terbium in the tetravalent state.

Pyridines are among the most prevalent heterocyclic motifs in approved pharmaceuticals. A general strategy enabling direct functionalization of the pyridine nitrogen in structurally complex molecules would provide a powerful means to diversify existing drugs into pyridinium salts and piperidines with minimal synthetic effort. However, current approaches typically require N-functionalization to be performed on simple pyridines, with molecular complexity introduced at later stages, where the available synthetic repertoire is limited. Here, we report a general strategy for the direct N-adamantylation of structurally more complex pyridines, including numerous drug molecules. The method is operationally simple and proceeds through the treatment of pyridine substrates with adamantyl acetate and Me3SiOTf. Mechanistic studies support initial N-silylation, followed by reaction with the alkyl acetate. Beyond pyridine adamantylation, the method extends to other N-heterocycles (pyrimidines, pyrazines, quinoxalines, and quinazolines) and alkyl groups, including systems that are too unstable to participate in conventional carbocation-based N-alkylation. Subsequent dearomatization provides access to N-alkyl piperidines. Evaluation of these previously inaccessible compounds for their in vitro ADME properties shows adequate solubility, permeability, and metabolic stability, supporting their potential utility in medicinal and agrochemical contexts.

Indium phosphide (InP) quantum dots (QDs) are already widely employed as heavy-metal-free materials for optoelectronic and bioimaging applications. However, common hot-injection methods produce zinc-blende phase InP QDs, and the synthesis of large-sized InP QDs with uniform size distribution and efficient near-infrared (NIR) emission has been limited. Here, starting from the cation-exchange synthesis of monodisperse wurtzite phase InP (w-InP) QDs with tunable size, we report the epitaxial growth of ZnSe/ZnS shells to significantly enhance photoluminescence (PL) efficiency and photochemical stability. The resulting w-InP/ZnSe/ZnS core/shell/shell (CSS) QDs exhibit narrow size-tunable bright NIR emission (∼740-820 nm). For example, for cores in the midrange (d = 8.7 ± 0.7 nm; peak emission wavelength at ∼780 nm), the PL quantum yield (QY) reaches 78%, with a narrow full-width at half-maximum (fwhm) of ∼33 nm (∼69 meV). Photostability studies reveal that the optical properties of both the w-InP core and the CSS QDs remain stable in ambient conditions under dark storage. Under illumination, the w-InP cores show increased PLQY due to light-induced surface oxidation, while in the presence of oxygen, CSS QDs experience a decline in PL performance due to photo-oxidation of the ZnSe shell. This degradation is lessened upon exposure to shorter wavelength light, suggesting the involvement of outer shell states in this process. These high-performance, cadmium-free NIR-emitting QDs thus hold strong potential for applications in advanced optoelectronics and bioimaging technologies.