ASAP (As Soon As Publishable)

Carbonyl-containing materials employed in state-of-the-art hybrid lead halide perovskite solar cells (PSCs) exhibit a strong structure-dependent electron donor effect that predominates in defect passivation. However, the impact of the molecular spatial conformation on the efficacy of carbonyl-containing passivators remains ambiguous, hindering the advancement of molecular design for passivating materials. Herein, we show that altering the spatial torsion angle of aromatic ketones from twisted to planar configurations, as seen in benzophenone (BP, 27.2°), anthrone (AR, 15.3°), and 9-fluorenone (FO, 0°), leads to a notable increment of the electron cloud density around the carbonyl group, thus improving the passivation ability for lead-based defects. Consequently, the PSC performance also relies on the torsion angle of the aromatic ketones, with the coplanar FO-based PSC achieving a highest power conversion efficiency (PCE) of 25.13% and retaining 92% of its initial efficiency after 1000 h of operation at the maximum power point under continuous 1-sun illumination (ISOS-L-1I). Moreover, a perovskite mini-module (14.0 cm²) containing FO exhibits a PCE of 20.19%. Our findings highlight the influence of molecular conformation on the passivation effect of the carbonyl group, offering deeper insight into the design and development of aromatic ketones as passivators for highly efficient and stable PSCs.

Photoredox catalysis is important in modern organic chemistry and the development of new synthetic methods. Mechanistic insights, particularly with photoredox chain reactions, are underdeveloped. This study combines quantum yield (QY) measurements, transient absorption spectroscopy (TAS), and electrochemical analysis to rigorously characterize the mechanism and rate constants of a ruthenium-catalyzed photoredox chain [4 + 2] cyclization between trans-anethole and isoprene. TAS and steady-state photochemical measurements (QY studies) reveal the role of oxygen in chain propagation as a secondary electron acceptor. The key kinetic competition between chain propagation and termination is identified by TAS and explored with kinetic modeling.

The structure of novel large pore borosilicate zeolite EMM-59 (|C₁₉H₄₂N₂|₈[B_5.2Si_218.8O₄₄₈]) with localized framework boron sites was determined by using three-dimensional electron diffraction (3D ED) and scanning transmission electron microscopy (STEM) imaging. EMM-59 was synthesized using 2,2-(cyclopentane-1,1-diyl)bis(N,N-diethyl-N-methylethan-1-aminium) as an organic structure-directing agent (OSDA). The framework has a three-dimensional intersecting channel system delimited by 12 × 10 × 10-ring openings and contains 28 T and 60 oxygen atoms in the asymmetric unit, making it the most complex monoclinic zeolite. The 3D ED data collected from as-made EMM-59 under cryogenic conditions revealed three symmetry-independent locations of the OSDAs, and STEM imaging showed that the OSDAs are flexible and adopt different molecular conformations in channels with identical structural environments. The framework boron atoms were exclusively found in T-sites of 4-rings, especially those shared by multiple 4-rings. The tetrahedral BO₄ with the highest boron content (38.6%) was transformed into a trigonal BO₃ after the OSDAs were removed upon calcination. Its location and boron content could also be identified by STEM imaging.

During chemical reactions, especially for electrocatalysis and electrosynthesis, the electric field is the most central driving force to regulate the reaction process. However, due to the difficulty of quantitatively measuring the electric field effects caused at the microscopic level, the regulation of electrocatalytic reactions by electric fields has not been well digitally understood yet. Herein, we took the infrared/Raman spectral signals of CO₂ molecules as descriptors to quantitatively predict the effects of different electric fields on the catalytic properties. Taking the metal-doped graphitic C₃N₄ (g-C₃N₄) catalyst as an example, we theoretically investigated the adsorption mode and energy of CO₂ molecules adsorbed on 27 distinct metal single-atom catalysts under different directions and intensities of electric field. Through a machine learning approach, a spectroscopy-property model between infrared/Raman spectral descriptors and adsorption energy/charge transfer was established, which quantified the facilitation of electric field effects on the CO₂ catalytic conversion. Meanwhile, based on the attention mechanism, the catalytic insight of the relationship between spectra and adsorption modes was mined, and the inverse prediction of electric field strength from spectra was realized. This work opens a new quantitative pathway for monitoring and regulating electrocatalytic reactions using machine learning spectroscopy.

Although diradicals should exhibit a rather small reaction barrier as compared to closed-shell species for activating kinetically inert molecules, the activation and functionalization of carbon dioxide with stable main-group diradicals remain virtually unexplored. In this work, we present a thorough study on CO₂ activation, reversible capture, and (de)oxygenation mediated by stable Group 14 singlet diradicals (i.e., diradicaloids) [(ADC)E]₂ (E = Si, Ge, Sn) based on an anionic dicarbene (ADC) framework (ADC = PhC{N(Dipp)C}₂; Dipp = 2,6-iPr₂C₆H₃). [(ADC)E]₂ readily undergo [4 + 2]-cycloadditions with CO₂ to result in barrelene-type bis-metallylenes [(ADC)E]₂(OC═O). The CO₂ addition is reversible for E = Ge; thus, CO₂ detaches under vacuum or at an elevated temperature and regenerates [(ADC)Ge]₂. [(ADC)Sn]₂(OC═O) is isolable but deoxygenates additional CO₂ to form [(ADC)Sn]₂(O₂CO) and CO. [(ADC)Si]₂(OC═O) is extremely reactive and could not be isolated or detected as it spontaneously reacts further with CO₂ to yield elusive monomeric Si(IV) oxides [(ADC)Si(O)]₂(CO_n) or carbonates [(ADC)Si(CO₃)]₂(CO_n) (n = 1 or 2) via the (de)oxygenation of CO₂. The molecular structures of all isolated compounds have been established by X-ray diffraction, and a mechanistic insight of their formation has been suggested by DFT calculations.

Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as para-substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits. As a counter-design, we report herein a generalized enantioselective synthesis of chiral diarylmethanes by means of an asymmetric migratory Tsuji–Wacker oxidation of simple stilbenes. The title protocol relies on the well-adjusted interplay of aerobic photoredox and selenium-π-acid catalysis to allow for the installation of a broad variety of arenes, including isosteric ones, into the methane core. Facial differentiation and regioselectivity are solely controlled by the selenium catalyst, which (a) renders the E/Z-configuration of the stilbene substrates inconsequential and (b) permits the stereodivergent synthesis of both product enantiomers from a single catalyst enantiomer, simply by employing constitutionally isomeric starting materials. Altogether, this multicatalytic platform offers the target structures with high levels of enantioselectivity in up to 97% ee, which has also been successfully exploited in expedited syntheses of antihistaminic (R)- and (S)-neobenodine.

The thermal safety issues of currently available Ni-rich cathode-based power supplies brought in the development of all-solid-state batteries, yet the cascade reactions in Ni-rich materials and the chemo-mechanical degradation between the cathode and solid electrolyte diminished the cycle life. Here, by introducing a new heteroatom chemical competing diffusion strategy, we successfully stabilize the Ni-rich cathode and the contact face with an solid electrolyte. Combining extensive explorations in theoretical calculation and multiscale in/ex situ characterization, we elucidate the atomic-level chemical competing diffusion upon the topological lithiation of layered materials. The heteroatoms with higher binding energy to the coordinated oxygen served as the “oxygen anchor” in the bulk and alleviated the excessive oxygen oxidation through charge compensation, thus easing the chemical aggression of the solid electrolyte by evolved oxygen. Comparably, others were enriched in the surface and formed an ionic “diffusion regulator” with residual lithium, and the special ionic transfer regulation mechanism of the piezoelectric layer validly improved the interface compatibility with the solid electrolyte and weakened the space-charge layer in solid-state batteries. This helped the designed Ni-rich cathode-based sulfide solid-state battery exhibit excellent cyclability under 4.5 V (97.3% after 120 cycles). Our findings unlocked the structure–function relationship between the polarization field generated by the piezoelectric material and the electrode.

Extracellular and transmembrane proteins, which account for the products of approximately 40% of all protein-encoding genes in tumors, play a crucial role in shaping the tumor immunosuppressive microenvironment (TIME). While protein degradation therapy has been applied to membrane proteins of cancer cells, it has rarely been extended to immune cells. We herein report a polymeric nanolysosome targeting chimera (nano-LYTAC) that undergoes membrane protein degradation on M2 macrophages and generates a sonodynamic effect for combinational cancer immunotherapy. Nano-LYTAC is found to have higher degradation efficacy to the interleukin 4 receptor (IL-4R) compared to traditional inhibitors. More importantly, it is revealed that the effect of nano-LYTAC on the function of the M2 macrophage is concentration-dependent: downregulating CD206 expression and interleukin 10 (IL-10) secretion from M2 macrophages at low concentration, while triggering their apoptosis at high concentration. Moreover, nano-LYTAC is found to possess long tumor retention (>48 h), allowing for multiple sonodynamic treatments with a single dose. Such a synergistic sonodynamic immunotherapy mediated by nano-LYTAC effectively reprograms the TIME via inhibiting the functions of M2 macrophages and regulatory T cells (Tregs), as well as promoting the maturation of dendritic cells (DCs) and tumor infiltration of T effector cells (Teffs), completely suppressing tumor growth, inhibiting pulmonary metastasis, and preventing recurrence under preclinical animal models.

Adipose-derived lipid droplets (LDs) are rich in triacylglycerols (TAGs), which regulate essential cellular processes, such as energy storage. Although TAG accumulation and LD expansion in adipocytes occur during obesity, how LDs dynamically package TAGs in response to excessive nutrients remains elusive. Here, we found that LD lipidomes display a remarkable increase in TAG acyl chain saturation under calorie-dense diets, turning them conducive to close-packing. Using high-resolution X-ray diffraction, solid-state NMR, and imaging, we show that beyond size expansion LDs from mice under varied obesogenic diets govern fat accumulation by packing TAGs in different crystalline polymorphs. Consistently, LDs and tissue stiffen for high-calorie-fed mice with more than a 2-fold increase in elastic moduli compared to normal diet. Our data suggest that in addition to expanding, adipocyte LDs undergo structural remodeling by close-packing rigid and highly saturated TAGs in response to caloric overload, as opposed to liquid TAGs in a low-calorie diet. This work provides insights into how lipid packing within LDs can allow for the rapid and optimal expansion of fat during the initial stages of obesity.

Endohedral fullerenes are known for their exceptional ability to host metal clusters that contain unique bonding motifs. In this study, we report a facile strategy to synthesize a new family of clusterfullerenes, fluoride clusterfullerenes (FCFs). This work demonstrates that actinides and rare earth metals as well as alkaline earth metals can be encapsulated within a variety of fullerene cages, and these fullerenes can be obtained in their pristine form without additional functionalization methods. Notably, Th₂F@I_h(7)-C₈₀ and CaScF@C_s(6)-C₈₂ were isolated and their molecular structures and magnetic properties were characterized by X-ray single-crystal diffraction and multiple spectroscopic techniques as well as DFT calculations. These findings reveal that the unique internal addition of a single fluorine atom significantly alters the metal–metal bonding interactions of Th–Th and Ca–Sc. While Th₂@I_h(7)-C₈₀ hosts a σ² Th–Th bond, an unprecedented actinide–actinide (Th–Th) single electron metal–metal bond is formed inside Th₂F@I_h(7)-C₈₀ upon the internal addition of fluoride. Similarly, while a Ca–Sc single electron bond exists in CaSc@C_s(6)-C₈₂, which exhibits excellent molecular qubit properties, the addition of fluoride transforms the compound into a singlet. The present study not only highlights the successful synthesis of a novel family of FCFs, which will likely be an extensive family, it also shows that fluorine doping can induce novel metal–metal bonding motifs leading to potentially intriguing magnetic properties.

Mechanosensitive fluorescent probes are valuable tools for detecting changes in cellular mechanics and viscosity. While numerous mechanosensitive probes have been developed, the construction of molecular assemblies for probing cellular mechanics remains largely unexplored, possibly due to the challenges of designing assemblies with synergistic and integrated functionalities. Here, we report the design and synthesis of mechanosensitive molecular assemblies by integrating DNA frameworks with vibration-induced emission (VIE) probes to enable live-cell membrane tension imaging. The molecular assemblies consist of a rigid tetrahedral DNA framework anchored with prescribed numbers of VIE probes. We find that VIE probes on the DNA framework retain their ratiometric fluorescence response characteristics in aqueous systems and on lipidic model membranes. Importantly, VIE assemblies exhibit distinct cell membrane targeting behaviors depending on the number of contact points between the molecular assemblies and the cell membrane. Especially, trivalent molecular assemblies can inhibit the internalization of the probes by the cells, a property absent in free VIE and mono/divalent molecular assemblies, thereby achieving targeted and prolonged retention on the cell membrane. Using the trivalent molecular assemblies, we successfully achieve ratiometric fluorescence imaging of cell membrane tension using confocal laser scanning microscopy, revealing the potential of such multifunctional mechanical-sensitive probes for live-cell applications.

Non-heme iron (Fe^II), α-ketoglutarate (α-KG)-dependent oxygenases are a family of enzymes that catalyze an array of transformations that cascade forward after the formation of radical intermediates. Achieving control over the reaction pathway is highly valuable and a necessary step toward broadening the applications of these biocatalysts. Numerous approaches have been used to engineer the reaction pathway of Fe^II/α-KG-dependent enzymes, including site-directed mutagenesis, DNA shuffling, and site-saturation mutagenesis, among others. Herein, we showcase a novel ancestral sequence reconstruction (ASR)-guided strategy in which evolutionary information is used to pinpoint the residues critical for controlling different reaction pathways. Following this, a combinatorial site-directed mutagenesis approach was used to quickly evaluate the importance of each residue. These results were validated using a DNA shuffling strategy and through quantum mechanical/molecular mechanical (QM/MM) simulations. Using this approach, we identified a set of active site residues together with a key hydrogen bond between the substrate and an active site residue, which are crucial for dictating the dominant reaction pathway. Ultimately, we successfully converted both extant and ancestral enzymes that perform benzylic hydroxylation into variants that can catalyze an oxidative ring-expansion reaction, showcasing the potential of utilizing ASR to accelerate the reaction pathway engineering within enzyme families that share common structural and mechanistic features.

Xenon isotope nuclear magnetic resonance (¹²⁹Xe-NMR) spectroscopy has been widely used to evaluate the pore structure of materials. However, determining how to apply this technique to investigate porous carbon materials is sometimes challenging, partly due to the structural disorder and heterogeneity of the surface properties of these materials, and partly due to the lack of reliable methods for controlling and assessing the density of adsorbed Xe. In this study, we designed and constructed a temperature- and pressure-controllable ¹²⁹Xe-NMR system to evaluate the interaction between activated carbon (AC) and adsorbed Xe molecules. Based on a confirmation of surface-covering adsorption form of Xe molecules in AC pores, the extrapolation to the ordinate in plots of the surface area-normalized Xe adsorption amount (ρ_Xe) and measured ¹²⁹Xe-NMR chemical shifts of adsorbed Xe molecules, δ(Xe), to remove the influence of the Xe–Xe interaction allowed us to estimate the interaction between the AC pore surface and a single Xe molecule. These data confirmed that interactions between the pore surface and adsorbed Xe molecules depend on a parameter related to the AC pore size, regardless of the content of oxygen-containing surface functional groups, and an empirical equation to estimate the average pore size of ACs from the ¹²⁹Xe-NMR results was proposed. Downward deviations of the linear correlation between ρ_Xe and δ(Xe) were attributed to the influence of paramagnetism presumably derived from oxygen-containing functional groups on the surfaces of ACs and to changes in the adsorption form in low- and high-ρ_Xe regions, respectively. These findings confirm the suitability of ¹²⁹Xe NMR for pore size determination in porous carbon materials.

Optogenetics, a revolutionary technique utilizing light-sensitive proteins to control cellular functions with high spatiotemporal precision, presents a promising avenue for disease treatment; however, its application in cancer therapy remains constrained by limited research. Herein, we introduce a pioneering strategy for remote-controlled optogenetic cancer therapy, synergistically merging optogenetics with ion therapy, which incorporates ion self-supply, in situ ion channel construction, and near-infrared (NIR) light-activated ion therapy, facilitating remote and noninvasive manipulation of cellular activities in deep tissues and living animals. We report the facile synthesis of water-dispersible upconversion nanoparticle (UCNP)–metal–organic framework (MOF) nanohybrids capable of effectively delivering plasmid DNA to cancer cells, thereby enabling the in situ expression of photoactivatable cation channels. The pH-responsive MOF components serve as a reservoir for metal cations, which are released in the acidic microenvironment of tumors, while the UCNP components function as remote-controlled transducers, converting near-infrared (NIR) light into visible light to activate the cation channels and allowing the cancer influx of released metal cations for ion therapy. The proposed remote-controlled cancer optogenetic therapy demonstrates its effectiveness across multiple tumor models, including subcutaneous colon tumors, subcutaneous breast tumors, and orthotopic breast tumors. This study represents a significant step toward the realization of optogenetics in clinics, with substantial potential for advancing cancer therapy.

We show that 2-diynylpyridine and a Bpin-terminated monoyne or diyne will cross-react to form benzyne intermediates. These reactive intermediates are captured by various in situ trapping agents to give products of three-component reactions. Various control reactions, substrate modification, binding studies, and DFT analysis suggest that a small amount of a noncovalent Lewis acid–base complex is the active species within which the diyne and diynophile engage to produce the benzyne. Only a single isomeric benzyne is formed when a Bpin-diyne is used; this selectivity is rationalized by the geometric distortion seen in the DFT-computed diradical intermediate.

Here, we employed a variety of mass spectrometry (MS)-based approaches, both (glyco)peptide-centric and protein-centric, to resolve the complex glycoproteoform landscape of recombinant IgA1 produced in HEK293 cells. These key immunoglobulins harbor several N- and O-glycosylation sites, making them considerably more heterogeneous than their IgG counterparts. We provide quantitative data on the occupancy and glycan composition for each IgA1 glycosylation site. Combining all data, we revealed that IgA1 molecules consist of at least three distinct populations with varying N-glycosylation site occupancies at the C-terminal tailpiece, namely, one with both glycosylation sites occupied, another with both glycosylation sites unoccupied, and a third asymmetric population with one glycosylation site occupied and the other unoccupied, challenging the prevailing acceptance that IgA1 N-glycosylation is symmetrical. This finding is significant, given that the tailpiece is involved in interactions with the J-chain and the Polymeric Immunoglobulin Receptor, and in general as antibody glycosylation is a quality attribute that needs to be carefully monitored, as the presence and nature of these modifications can affect the antibody’s efficacy, lifetime, stability, and binding and/or neutralizing capacities. Optimizing strategies to produce recombinant IgA1 requires efficient and specific quality control analytical strategies, as presented here, which is essential for therapeutic IgA1-based antibody development. We expect that the integrated MS-based strategy presented here may be beneficial to comprehensively characterize the glycoproteoform profiles of IgA1-based therapeutics, thereby improving their production and optimization processes and facilitating the pathway to bring more IgA1-based therapeutics into clinical applications.

Chiral cyclopentadienyl (Cp^X) metal complexes are frequently used in asymmetric catalysis by virtue of their high reactivity and selectivity. Planar-chiral-only rhodium and iridium cyclopentadienyl complexes are particularly promising due to unrestricted chemical space for Cp^X ligand design while retaining structural simplicity. However, they are currently still niche because of a lack of efficient synthetic strategies that avoid lengthy chiral auxiliary routes or chiral preparatory HPLC resolution of the complexes. To streamline access to such planar-chiral-only Cp^X-metal complexes, we designed a straightforward, highly enantiospecific, point-to-planar chirality transfer complexation via facially selective concerted-metalation-deprotonation between metal-carboxylate precursor [M(olefin)₂OAc]₂ and a chiral cyclopentadiene. This entirely avoids the typical stereoablative complexation of an achiral cyclopentadienyl anion that detrimentally yields a racemate. Exploiting the described enantiospecific complexation protocol and a simple divergent synthetic route to suitable chiral cyclopentadienes, we generated a structurally diverse library of new planar chiral Cp-Rh(I), Cp-Ir(I), Cp-Rh(III), and Cp-Ir(III) complexes. Moreover, the enantiospecific complexation step can be concatenated with a preceding Au-catalyzed cyclization in an efficient one-pot process that likely involves an elaborate point-to-axial-to-point-to-planar chirality transfer. Guided by computational selectivity predictions, the structure of a Cp^X-Rh complex in our library was tuned to optimize reactivity and selectivity in the asymmetric C–H functionalization of a benzamide with various challenging alkenes. With an optimized Cp^X-Rh complex in hand, we showcased its excellent catalytic performance and high selectivity for refractory alkene substrates that reacted in poor selectivity with previous Cp^X-Rh catalysts.

We report a copper-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of allyl bromides using 1,1-diborylalkanes as prochiral nucleophiles. This methodology employs copper(I) bromide as a catalyst, an (R)-BINOL-derived phosphoramidite as a ligand, and lithium benzoate as a crucial additive. The reaction affords enantioenriched homoallylic boronic esters possessing vicinal stereocenters in good yields and high diastereo- and enantioselectivity. The developed method demonstrates a broad substrate scope with respect to a wide range of 1,1-diborylalkanes and allyl bromides. Mechanistic studies, including deuterium-labeling experiments and DFT calculations, provide insights into the reaction pathway and the origin of the stereoselectivity. The synthetic utility of this method is showcased through various transformations of the obtained enantioenriched homoallylic boronic esters into valuable chiral building blocks.

The semiconductor properties of nanosized graphene fragments, known as molecular nanographenes, position them as exceptional candidates for next-generation optoelectronics. In addition to their remarkable optical and electronic features, chiral nanographenes exhibit high dissymmetry factors in circular dichroism and circularly polarized luminescence measurements. However, the synthesis of enantiomerically pure nanographenes remains a significant challenge. Typically, these materials are synthesized in their racemic form, followed by separation of the enantiomers using high-performance liquid chromatography (HPLC). While effective, this method often requires expensive instrumentation, extensive optimization of separation conditions, and typically yields analytical quantities of the desired samples. An alternative approach is the enantioselective synthesis of chiral molecular nanographenes; however, to date, only two examples have been documented in the literature. In this work, we present a straightforward chemical method for the chiral resolution of helical bilayer nanographenes. This approach enables the effective and scalable preparation of enantiomerically pure nanographenes while avoiding the need for HPLC. The incorporation of a BINOL core into the polyarene precursor facilitates the separation of diastereomers through esterification with enantiomerically pure camphorsulfonyl chloride. Following the separation of the diastereomers by standard chromatographic column, the hydrolysis of the camphorsulfonyl group yields enantiomerically pure nanographene precursors. The subsequent graphitization, achieved through the Scholl reaction, occurs in an enantiospecific manner and with the concomitant formation of a furan ring and a heterohelicene moiety. The absolute configurations of the final enantiomers, P-oxa[9]HBNG and M-oxa[9]HBNG, have been determined using X-ray diffraction. Additionally, electrochemical, photophysical, and chiroptical properties have been thoroughly evaluated.

The subcellular distribution of cargoes plays a crucial role in determining cell fate and therapeutic efficacy. However, achieving the precise delivery of therapeutics to specific intracellular targets remains a significant challenge. Here, we present a trimodular and acid/enzyme-gated nanoplatform (TAEN) that undergoes disassembly within acidic endosomes and then is cleaved by lysosomal cathepsin B to facilitate efficient and targeted transport of released cargoes into mitochondria compartments. By utilizing this nanovehicle, we successfully achieve selective sorting of photosensitizer molecules into mitochondria with a colocalization coefficient of up to 0.98, leading to the generation of reactive oxygen species stress specifically within the mitochondria for potent pyroptosis-based cancer therapy. The induction of mitochondrial stress triggers the intrinsic apoptotic pathway as well as caspase-3/gasdermin-E (GSDME) cascade, resulting in an enhanced cancer cell killing efficacy by nearly 2 orders of magnitude as compared to lysosomal stress. Furthermore, due to its superior capability to stimulate both innate and adaptive immune responses, our mitochondria-sorted nanophotosensitizer exhibits robust antitumor immune efficacy in multiple tumor-bearing mice models. This study not only provides insights into engineering nanomedicines for subcellular targeted delivery but also offers a valuable toolkit for advanced research in the field of nanobiology at subcellular resolution.

The hyperpolarization of biological samples using dissolution dynamic nuclear polarization (dDNP) has become an attractive method for the monitoring of fast chemical and enzymatic reactions using NMR by taking advantage of a large signal increase. This approach is actively developing but still needs key methodological breakthroughs to be used as an analytical method for the monitoring of complex networks of simultaneous metabolic pathways. In this article, we use the deceptively simple example of glucose-6-phosphate (G6P) oxidation reaction by the enzyme G6P dehydrogenase (G6PDH) to discuss some important methodological aspects of dDNP kinetic experiments, such as its robustness and its ability to provide repeatable results as well as the capacity of this time-resolved methodology to test kinetic models and hypotheses and to provide reliable parameter estimates. To illustrate the potential of our approach, we report the first direct and quantitative evidence of selectivity of G6PDH toward the β anomer of G6P.

Cyclohexane (Cy), commonly produced by the catalytic hydrogenation of benzene (Bz), is used in large quantities as a solvent or feedstock for nylon polymers. Removing trace unreacted Bz from the Cy product is technically difficult due to their similar molecular structures and physical properties. Herein, we report that a metal–organic framework (MOF) adsorbent shows a molecular sieving effect for Bz and Cy with record-high Bz/Cy adsorption selectivities (216, 723, and 1027) in their liquid mixtures (v/v = 1:1, 1:10, and 1:20), and traps Bz molecules effectively even at low partial pressure in the vapor phase (e.g., 2.49 mmol/g at 8.2 Pa) or at low content in liquid-phase Cy (e.g., 128 mg/g at 20 ppm). Over 99% removal of trace Bz (1000 ppm) from liquid Cy could be achieved in one simple stripping step at room temperature using this sorbent, producing a Cy with >99.999% purity. Single-crystal structure analyses for guest-free and Bz-loaded phases of the MOF disclosed that a narrow slit-like pore aperture and the strong uniting of multiple weak host–guest and guest–guest interactions are the co-origin of its distinct adsorption property for Bz and Cy.

Active compound protection can allow inherently unstable molecules to be stabilized and latent reactivity to be masked. Synthetic receptors are attractive in terms of providing such protection. Nevertheless, preserving the activity and functionality of organic molecules in water poses a challenge. Here, we show that biomimetic receptors, specifically amide naphthotubes and an amide anthryltube, allow the efficient preservation of functional organic molecules in water. In particular, the amide naphthotubes were found to extend the half-lives of acetal-containing substrates (“acetals”) against acid-catalyzed hydrolysis by up to 3000 times. This kinetic protection effect was ascribed to hydrogen bond-based recognition of the organic guests. A substrate dependence was seen that was further exploited to achieve the kinetic resolution of acetal isomers. To the best of our knowledge, the present study constitutes one of the most effective acetal protection strategies reported to date. The recognition-based protection approach reported here appears generalizable as evidenced by the protection of eight different substrates against six distinct chemical reactions. Based on the present findings, we propose that it is possible to design receptors that provide for the protection of specific substrates under a variety of reaction conditions including those carried out in water.

Solid-phase peptide synthesis (SPPS) and native chemical ligation (NCL) are powerful methods for obtaining peptides and proteins that are otherwise inaccessible. Nonetheless, numerous sequences are difficult to prepare via SPPS, and cleaved peptides often have low aqueous solubility. To address these challenges, we developed a “Synthesis Tag” consisting of six arginines connected to the target sequence via a cleavable MeDbz linker. “SynTag” effectively improves batch- and flow-SPPS of “difficult sequences”, enhances the solubility of the cleaved peptides, and provides direct access to native sequences by hydrolysis, or peptide thioesters for NCL. We demonstrate its utility in the first chemical synthesis of the MYC transactivation domain with a single NCL. We envisage SynTag to become a broadly applicable tool that enables the synthesis and study of previously unattainable peptides and proteins.

The trifluoromethyl (−CF₃) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made in the development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze the formation of C(sp³)–CF₃ bonds. In this work, we demonstrate that a nonheme iron enzyme, hydroxymandelate synthase from Amycolatopsis orientalis (AoHMS), is capable of generating CF₃ radicals from hypervalent iodine(III) reagents and directing them for enantioselective alkene trifluoromethyl azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling the rapid evaluation of AoHMS variants for this abiological transformation. The final optimized variant accepts a range of alkene substrates, producing the trifluoromethyl azidation products in up to 73% yield and 96:4 enantiomeric ratio (e.r.). The biocatalytic platform can be further extended to alkene pentafluoroethyl azidation and diazidation by altering the iodine(III) reagent. In addition, anion competition experiments provide insights into the radical rebound process for this abiological transformation. This study not only expands the catalytic repertoire of metalloenzymes for radical transformations but also creates a new enzymatic space for organofluorine synthesis.

Safely and effectively harnessing innate immunity to boost cancer immunotherapy is promising yet challenging. Hence, we have developed a series of programmable aptamer-based multispecific engagers by encoding various artificial aptamer-drug codons with DNA-templated polymerization, aiming to broadly boost innate and adaptive immunity for antitumor therapy. All circular single-stranded multivalent aptamer-drug conjugates (os-mvApDCs) had a dendritic structure, precise size, and excellent stability, enabling prolonged blood circulation, targeted tumor accumulation, and rapid multireceptor-mediated endocytosis. A trispecific engager (^Sl/Pd/Mjos-mvApDCs^SMT), targeting PD-1 on CD8⁺ T cells and PD-L1/c-Met on tumor cells, recruited large amounts of immune cells into the tumor and released cytotoxic MMAE and immunomodulators, inducing severe cell death and broad activation of innate immunity. When combined with the αPD-1 blockade, there was a significant increase in the number of CD8⁺ T cells (10-fold increase versus untreated control) engaged and expanded in the tumor, exhibiting potent function (IFN-γ⁺/GzmB⁺) and low exhaustion (PD-1⁺TIM-3⁺). The orchestrated innate and adaptive immunity effectively eliminated immunosuppressive MDSCs, Tregs, and M2-like macrophages in tumors and promoted the maturation of dendritic cells (DCs) in the draining lymph nodes, resulting in robust and durable systemic antitumor efficacy, with 7 out of 8 mice surviving over 60 days. Our programmable DNA-templated printing technology enables the rational design of multispecific therapeutics with modular composition and function but minimal production issues, providing a versatile tool for the development of multifunctional personalized medicine.

CoSn and FeSn, two kagome-lattice metals, have recently attracted significant attention as hosts of electronic flat bands and emergent physical properties. However, current understandings of their physical properties are limited to knowledge of the average crystal structure. Here, we report the Fe-doping induced coemergence of the antiferromagentic (AFM) order and local symmetry breaking in (Co_0.45Fe_0.55)Sn. Rietveld analysis on the neutron and synchrotron X-ray diffraction data indicates A-type antiferromagnetic order with the moment pointing perpendicular to the kagome layers, associated with the anomaly in the MSn(1)₂Sn(2)₄ (M = Co/Fe) octahedral distortion and the lattice constant c. Reverse Monte Carlo (RMC) modeling of the synchrotron X-ray total scattering results captured the subtle local orthorhombic distortion involving off-axis displacements of Sn(2). Our results indicate that the stable hexagonal lattice above T_N becomes unstable once the A-type AFM order is formed below T_N. We argue that the local symmetry breaking has a magnetic origin, since the spatially varied M–Sn(2) bond lengths arise from out-of-plane magnetic exchange coupling J_c via the exchange pathway M–Sn(2)–M. Our study provides comprehensive information on the crystal structure in both long-range scale and local scale, unveiling unique coupling between AFM order, octahedral distortion, and hidden local symmetry breaking.

Single molecules bridging two metallic electrodes can emit light through electroluminescence when subjected to a bias voltage. Typically, light emission in such devices results from transitions between molecular states, although in the presence of light-matter coupling, the emission can result from a transition between hybrid light-matter states. Here, we create single metal-molecule-metal junctions and simultaneously collect conductance and electroluminescence data using a scanning tunneling microscope (STM) equipped with a custom spectrometer. Through experimental analysis and electronic structure calculations, we provide evidence for a molecule-electrode interfacial exciton coupled to a junction cavity plasmon. Importantly, we find that close to resonant transport conditions, the molecular junction functions as a single emitter that is strongly coupled to the junction cavity mode, leading to characteristic Rabi splitting of the emission spectrum and providing the first example of an electroluminescence-driven single-molecule system in the regime of strong light-matter coupling.

Symmetry is a motif featured in almost all areas of science, and understanding the mechanism of symmetry breaking is challenging. Similar to mutations that disrupt symmetry in evolution, defects in materials offer insight into symmetry breaking. Here, we investigate symmetry in intragenerational mutations and symmetry breaking in transgenerational mutations in the evolutionary growth system of carbon nanotubes (CNTs). Mutations caused by pentagon–heptagon (5–7) pairs in different conformations shorten the lifespans of single-walled carbon nanotubes (SWNTs) by acting as time markers during growth. Symmetric distributions are observed for intragenerational mutations from (n, m) to (n + i, m–i) (where i ∈ caslon Z) with different appearance orders of pentagon and heptagon. Such symmetry breaks occur in transgenerational mutations. Intragenerational mutations occur multiple times on a SWNT, oscillating regularly between i and – i until termination occurs. These types and effects are retained in the form of memory to encode SWNTs during subsequent growth, resulting in a length reduction after each mutation. Our results provide a profound understanding of symmetry breaking and memory retention and offer guidance for the controlled synthesis of materials.

The development of small-molecule catalysts that can effectively activate both reacting partners simultaneously represents a pivotal pursuit in advancing the field of stereoselective glycosylation reactions. We report herein the development of the singly protonated form of readily available phenanthroline as an effective cooperative catalyst that facilitates the coupling of a wide variety of aliphatic alcohols, phenols, and aromatic amines with α-glycosyl trichloroacetimidate donors. The glycosylation reaction likely proceeds via an S_N2-like mechanism, generating β-selective glycoside products. The developed protocol provides access to O- and N-glycosides in good yields with excellent levels of β-selectivity and enables late-stage functionalization of O- and N-glycosides via cross-coupling reactions. Importantly, this method exhibits excellent β-selectivity that is unattainable through a C2-O-acyl neighboring group participation strategy, especially in the case of glycosyl donors already containing a C2 heteroatom or sugar unit. Kinetic studies demonstrate that the byproduct trichloroacetamide group plays a previously undiscovered pivotal role in influencing the reactivity and selectivity of the reaction. A proposed mechanism involving simultaneous activation of the glycosyl donor and acceptor by the singly protonated phenanthrolinium salt catalyst with the assistance of the trichloroacetamide group is supported by kinetic analysis and preliminary computational studies. This cooperative catalysis process involves four consecutive hydrogen bond interactions. The first interaction occurs between the carbonyl oxygen of the trichloroacetamide group and the hydroxyl group of alcohol nucleophile (C═O···HO). The second involves the trichloroacetamide-NH₂ forming a hydrogen bond with the nitrogen atom of the phenanthroline (NH···N). The third involves the donor trichloroacetimidate (═NH) engaging in a hydrogen bond interaction with the phenanthrolinium-NH (NH···N═H). Lastly, the protonated trichloroacetimidate-NH₂ forms a hydrogen bond with the fluorine atom of the tetrafluoroborate ion.

Aerobic oxidation of a dimethylplatinum(II) complex featuring 1,1-di(2-pyridyl)ethanol as a supporting ligand leads to the formation of two unexpected Pt^IV complexes (in ∼1:1 ratio), neither of which results from direct oxidation typical for Pt^II centers supported by popular κ²-(N,N) ligands. While one product features an isomerized Pt^IV center stabilized by the κ³-(N,N,O) ligand coordination mode, surprisingly, the other product results from intramolecular activation of the ligand methyl fragment. Mechanistic studies, reactivity of model complexes, and DFT calculations reveal that the critical proton-responsive nature of the ligand allows formation of intermediates that result in a concerted metalation deprotonation (CMD)-like C–H activation at Pt^IV. To the best of our knowledge, this is the first mechanistic delineation of Csp³-H activation at Pt^IV, despite being known for other high-valent platinum group metal centers.

The development of materials with high ambipolar mobility is pivotal for advancing multifunctional applications, yet such materials remain scarce. Presently, cubic boron arsenide (BAs) stands out as the premier ambipolar material, demonstrating an ambipolar mobility of ∼1600 cm² V^–1 s^–1 at room temperature [Science 2022, 377, 433 and Science 2022, 377, 437]. Herein, we illustrate that semiconducting Al₂B₁₂C, featuring a nonclathrate B–C framework in which a C atom bonds to the vertices of four distorted hexagonal antiprism B₁₂ units via quasi-sp³ hybridization, is predicted to possess ambipolar carrier transport behavior. Its ambipolar mobility can reach up to ∼2095 cm² V^–1 s^–1. The hole transport originates from the C p_z orbitals that trap the electrons of Al atoms at the valence band maximum, forming a C–Al–C hole channel along the c-axis direction, whereas electron transport stems from the π electrons in B₁₂ units. For Al₂B₁₂C, polar optical phonon scattering serves as the primary mechanism limiting mobility. Additionally, it displays a high absorption coefficient (10⁵ cm^–1) in the visible spectrum. These appealing properties make Al₂B₁₂C a highly promising environmentally friendly semiconductor for applications in electronics and photovoltaic devices.

Mechanical fatigue of the binders during the repeated volume change of Si-based anodes induces binder network collapse, resulting in lithium-ion batteries (LIBs) failing prematurely. Herein, we designed a damageless polymer binder with a mechanically interlocked network utilizing [an]daisy chains (^DCMIN) and poly(acrylic acid) (PAA) to improve the structural cohesion of the Si-based anode. This ^DCMIN@PAA binder exhibits robust mechanical properties, high elasticity, and excellent adhesion. More importantly, the recognition between the dialkylammonium salt decorated on the thread component and the ether group of benzo-24-crown-8 provides efficacy for the ^DCMIN@PAA binder in quickly dissipating energy and reducing damage accumulation. Therefore, with the ^DCMIN@PAA binder, the pure-Si anode showcases high retention over 1050 cycles at 1 C and a fast rate response (5 C). The ^DCMIN@PAA binder also improves the cycling stability of the homemade pouch cell using a pure-Si anode. In addition, the water-soluble ^DCMIN@PAA binder, capable of quick release and separation, could facilitate recycling of the end-of-life anode, enhancing the sustainability of the battery. This work highlights the indispensability of energy dissipation with the consideration of a binder and provides a viable path forward to stabilize Si-based anodes suffering from volume change-induced stress accumulation.

Building artificial neurons and synapses is key to achieving the promise of energy efficiency and acceleration envisioned for brain-inspired information processing. Emulating the spiking behavior of biological neurons in physical materials requires precise programming of conductance nonlinearities. Strong correlated solid-state compounds exhibit pronounced nonlinearities such as metal–insulator transitions arising from dynamic electron–electron and electron–lattice interactions. However, a detailed understanding of atomic rearrangements and their implications for electronic structure remains obscure. In this work, we unveil discontinuous conductance switching from an antiferromagnetic insulator to a paramagnetic metal in ε-Cu_0.9V₂O₅. Distinctively, fashioning nonlinear dynamical oscillators from entire millimeter-sized crystals allows us to map the structural transformations underpinning conductance switching at an atomistic scale using single-crystal X-ray diffraction. We observe superlattice ordering of Cu ions between [V₄O₁₀] layers at low temperatures, a direct result of interchain Cu-ion migration and intrachain reorganization. The resulting charge and spin ordering along the vanadium oxide framework stabilizes an insulating state. Using X-ray absorption and emission spectroscopies, assigned with the aid of electronic structure calculations and measurements of partially and completely decuprated samples, we find that Cu 3d and V 3d orbitals are closely overlapped near the Fermi level. The filling and overlap of these states, specifically the narrowing/broadening of V 3d_xy states near the Fermi level, mediate conductance switching upon Cu-ion rearrangement. Understanding the mechanisms of conductance nonlinearities in terms of ion motion along specific trajectories can enable the atomistic design of neuromorphic active elements through strategies such as cointercalation and site-selective modification.

Chemokines are small proteins involved in recruiting leukocytes to sites of inflammation via interactions with specific cell surface receptors. CCL22 is a chemokine known to play a critical role in inflammatory diseases such as atopic dermatitis and asthma; inhibition of this chemokine therefore represents an attractive therapeutic strategy. Herein, we describe the discovery of cyclic d-sulfopeptide inhibitors of CCL22 identified through mirror-image mRNA display with genetic reprogramming. Chemical synthesis of mirror-image d-CCL22 enabled screening of a cyclic peptide library comprised of all l-amino acids, with reprogramming of l-sulfotyrosine to mimic the presence of this post-translational modification on native chemokine receptors. Enriched macrocyclic peptides were prepared in their mirror-image d-form and assessed for binding against native l-CCL22. The most potent ligand, a plasma-stable d-cyclic peptide bearing four d-sulfotyrosine residues, exhibited nanomolar affinity for CCL22, high selectivity over other chemokines, and nanomolar inhibition of CCL22 signaling through CCR4. This work highlights the vast potential of mirror-image mRNA display technology for discovering proteolytically stable d-peptide inhibitors of protein–protein interactions relevant across a range of therapeutic indications.

The carbonylative polymerization of olefin yields aliphatic polyketones, which are used as engineering plastics in the market due to their excellent mechanical strength, chemical resistance, and surface and barrier properties. However, the usage of precious palladium catalysts has restricted their extensive application as commodity materials. Herein, we present a series of phosphine-sulfonate Ni catalysts with a wide spectrum of electronic and steric substituents on the phosphorus moiety for the carbonylative polymerization of ethylene. Such efficient nickel-catalyzed copolymerization shows the on-demand transformation of ethylene/CO gas to polyketones with quantitative yield and product specificity. A remarkable productivity of up to 20 kg PK (g Ni)⁻¹ was obtained during ethylene/propylene/CO terpolymerization, and the polymerization productivity is independent of the type and feeding amount of α-olefin. The resulting terpolymers show comparable crystallinity, thermal stability, and tensile properties with commercial POKETONE products from Hyosung. The nickel catalyst also features the advantages of using cheap raw material sources and simple synthetic procedures that can be scaled up easily, which enables it to be a promising candidate for industrial application.

Adiabatic demagnetization refrigeration (ADR) based on the magnetocaloric effect (MCE) is a promising technique to achieve cryogenic temperature. However, magnetic entropy change (ΔS_M), the driving force of ADR, remains far below theoretical −ΔS_M = nRln(2J + 1)/M_W for most magnetic refrigerants. Here, we report giant MCE in orthorhombic EuCl₂, where a ferromagnetic ground state with excellent single-ion behavior of Eu²⁺ and free spins has been demonstrated by combining ab initio calculations with Brillouin function analysis and magnetic measurements. Consequently, a record-high −ΔS_M ∼ 74.6 J·kg^–1·K^–1 (1.8 K) at 5 T was experimentally achieved, approaching 96% of the theoretical limit (77.5 J·kg^–1·K^–1). At a lower field of 1 T, EuCl₂ also achieves the highest-ever record of −ΔS_M ∼ 36.8 J·kg^–1·K^–1. Further, direct quasi-adiabatic demagnetization measurements demonstrate that its large −ΔS_M allows EuCl₂ to maintain a long holding time at sub-Kelvin temperature (∼346 mK), surpassing all previously reported materials. These superior magnetocaloric performances position EuCl₂ as an attractive cryogenic refrigerant.

Recent advancements in on-surface synthesis have enabled the reliable and predictable preparation of atomically precise low-dimensional materials with remarkable properties, which are often unattainable through traditional wet chemistry. Among these materials, porphyrins stand out as a particularly intriguing class of molecules, extensively studied both in solution and on surfaces. Their appeal lies in the ability to fine-tune their unique chemical and physical properties through central metal exchange or peripheral functionalization. However, the synthesis of π-extended porphyrins featuring unsubstituted anthracenyl groups has remained elusive. Herein, we report an in vacuo temperature-controlled cyclodehydrogenation of bis- and tetraanthracenyl Zn(II) porphyrins on a gold(111) surface. By gradually increasing the temperature, sequential dehydrogenation leads to the formation of fused anthracenyl porphyrin products. Notably, at high molecular coverage, the formation of bowl-shaped porphyrins occurs, along with transmetalation of Zn with Au. These findings open the door to a variety of π-extended anthracenyl-containing porphyrin products via cyclodehydrogenation and transmetalation, offering significant potential in the fields of molecular (photo/electro)catalysis, (opto)electronics, and spintronics.

Cellular context profiling of modification effector proteins is critical for an in-depth understanding of their biological roles in RNA N⁶-methyladenosine (m⁶A) modification regulation and function. However, challenges still remain due to the high context complexities, which call for a versatile toolbox for accurate live-cell monitoring of effectors. Here, we propose a demethylation-switchable aptamer sensor engineered with a site-specific m⁶A (DSA-m⁶A) for lag-free monitoring of the m⁶A demethylase FTO activity in living cells. As a proof of concept, a DNA aptamer against adenosine triphosphate (ATP) is selected to construct the DSA-m⁶A model, as the “universal energy currency” role of ATP could guarantee the equally fast and spontaneous conformation change of DSA-m⁶A sensor upon demethylation and ATP binding in living organisms, thus enabling sensitive monitoring of FTO activity with neither time delay nor recourse to extra supply of substances. This ATP-driven DSA-m⁶A design facilitates biomedical research, including live-cell imaging, inhibitor screening, single-cell tracking of dynamic FTO nuclear translocation upon starvation stimuli, FTO characterization in a biomimetic heterotypic three-dimensional (3D) multicellular spheroid model, as well as the first report on the in vivo imaging of FTO activity. This strategy provides a simple yet versatile toolbox for clinical diagnosis, drug discovery, therapeutic evaluation, and biological study of RNA demethylation.

Since ether moieties are often found not only in petrochemical products but also in natural organic molecules, the development of methods for manipulating C–O bonds of ethers is important for expanding the range of compound libraries synthesized from biomass resources, which should contribute to the goal of carbon neutrality. We report herein that gold nanoparticles supported on Lewis acidic metal oxides, namely α-Fe₂O₃, showed excellent catalytic activity for the reaction of dialkyl ethers and diborons, which enables the conversion of unactivated C(sp³)–O bonds to C(sp³)–B bonds at around room temperature. Various acyclic and cyclic ethers as well as a series of diborons participated in the heterogeneous gold-catalyzed borylation of unactivated C(sp³)–O bonds, to give a series of alkylboronates in high yields. Mechanistic studies corroborated that the present borylation of C(sp³)–O bonds of dialkyl ethers proceeded at the interface between gold nanoparticles and Lewis acidic metal oxides. Furthermore, adsorption IR measurements supported the notion that strong Lewis acid sites were generated at the boron atom of diborons adsorbed at the interface between Lewis acidic metal oxides and gold nanoparticles, which enabled us to ensure that the cooperation of gold nanoparticles and Lewis acidic metal oxides was responsible for the efficient transformation of unactivated C(sp³)–O bonds in ethers under mild conditions. This novel reaction technology which is specific to heterogeneous catalysts enables the activation of stable C(sp³)–O bonds of oxygenated chemical feedstock, which is beneficial for the sustainable synthesis of value-added organoboron compounds.

Photoelectrochemical (PEC) water splitting provides a promising strategy for H₂ production. However, its performance is limited by severe carrier recombination and sluggish water oxidation kinetics. While numerous strategies, namely, elemental doping, morphology engineering, heterojunction formation, and catalyst modification, have been extensively explored to enhance the PEC performance, the application of external magnetic fields (MFs) to affect the catalysis or charge carrier dynamics remains yet to be exploited. Herein, BiVO₄ is first selected as a representative photoanode, demonstrating that an ultrathin ferromagnetic coating based on Fe₂TiO₅, when combined with an external MF, boosts its solar water oxidation performance. The combined analyses of the charge transfer and separation efficiency together with ultraviolet photoelectron spectroscopy and transient absorption spectroscopy data revealed that the MF positively affects the band alignment across the BiVO₄/Fe₂TiO₅ interface, improving the charge separation, while the oxygen evolution at the Fe₂TiO₅/electrolyte interface was promoted. Finally, we expand this concept to other metal oxide photoanodes, such as TiO₂, WO₃, and Fe₂O₃, demonstrating the universality of such an approach. Overall, this work pioneers a novel route to harvest external MFs and improve the PEC response of common nonmagnetic semiconductor photoelectrodes in photoelectrocatalytic conversion.

The synthesis of amides from amines and carboxylic acids is the most widely carried out reaction in medicinal chemistry. Yet, most amide couplings are still conducted using stoichiometric reagents, leading to significant waste; few synthetic catalysts for this transformation have been adopted industrially due to their limited scope and/or poor recyclability. The majority of catalytic approaches focus on a single activation mode, such as enhancing the electrophilicity of the carboxylic acid partner using a Lewis acid. In contrast, nature effortlessly forges and breaks amide bonds using precise arrays of Lewis/Brønsted acidic and basic functional groups. Drawing inspiration from these systems, herein we report a simple defect engineering strategy to colocalize Lewis acidic Zr sites with other catalytically active species within porous metal–organic frameworks (MOFs). Specifically, the combination of pyridine N-oxide and Zr open metal sites within the defective framework MOF-808-py-Nox produces a heterogeneous catalyst that facilitates amide bond formation with broad functional group compatibility from amines and carboxylic acids, esters, or primary amides. Extensive density functional theory (DFT) calculations using cluster models support that the formation of a hydrogen-bonding network at the defect sites facilitates amide bond formation in this material. MOF-808-py-Nox can be recycled at least five times without losing significant crystallinity, porosity, or catalytic activity and can be employed in continuous flow. This defect engineering strategy can be potentially generalized to produce libraries of catalytically active MOFs with different combinations of colocalized functional groups.

Electrochemical systems with increasing complexity are gaining importance in catalytic energy conversion applications. Due to the interplay between transport phenomena and chemical kinetics, predicting optimization is a challenge, with numerous parameters controlling the overall performance. Zone diagrams provide a way to identify specific kinetic regimes and track how variations in the governing parameters translate the system between either adverse or optimal kinetic states. However, the current procedures for constructing zone diagrams are restricted to simplified systems with a minimal number of governing parameters. We present a computationally based method that maps the entire parameter space of multidimensional electrochemical systems and automatically identifies kinetic regimes. Once the current output over a discrete set of parameters is interpreted as a geometric surface, its geometry encodes all of the information needed to construct a zone diagram. Zone boundaries and limiting zones are defined by curved and flat regions, respectively. This geometric framework enables a systematic exploration of the parameter space, which is not readily accessible by analytical or direct numerical methods. This will become increasingly valuable for the rational design of electrochemical systems with intrinsically high complexity.

Molten salt reactors are an emerging advanced nuclear reactor concept in which the fuel is dissolved into the working fluid in the form of a high-temperature molten salt. The complex, mobile, and corrosive nature of this fluid presents a fundamental challenge for analytical measurements. Tracking species throughout the reactor is important for ensuring proper operation. This article presents laser-induced breakdown spectroscopy (LIBS) used to monitor the elemental composition of a molten salt and corresponding hydrogen isotopic shifts in real-time. A NaNO₃–KNO₃ eutectic salt was saturated with protium and deuterium gases, then the effluent aerosol stream formed using an argon sparging vessel was monitored with LIBS. This modular LIBS system permitted several spectrometers to be used simultaneously to capture high-resolution isotopic shifts and provide broadband elemental coverage. The results exhibit how LIBS can be used to understand salt–gas chemical and physical interactions such as diffusion. Furthermore, LIBS’ broad elemental coverage can provide greater insight into the chemical reactions within the salt vessel such as the formation of water vapor by monitoring hydrogen and oxygen signatures simultaneously. Ultimately, this study demonstrates the analytical possibilities of LIBS for real-time monitoring of isotopes and elemental composition in molten salt systems.

Polymer design requires fine control over syntheses and a thorough understanding of their macromolecular structure. Herein, near-atomic level imaging of polymers is achieved, enabling the precise determination of one of the most important macromolecular characteristics: molecular weight. By judiciously designing and synthesizing different linear metal(loid)-rich homopolymers, subnanoscale polymer imaging is achieved through annular dark field-scanning transmission electron microscopy (ADF-STEM), owing to the incorporation of high Z atoms in the side chain of the monomeric units. The molecular weight of these polymers can be precisely determined by detecting and counting their metal(loid) atoms upon ADF-STEM imaging, at sample concentrations as low as 10 μg·mL^–1. Notably, a commonly used C, H, and O-containing polymer (i.e., poly(methyl acrylate)) that was thus far inaccessible at the atomic scale is derivatized to allow for subnano-level imaging, thus expanding the scope of our approach toward the atomic-level visualization of commodity polymers.

Degradable polymers are an emerging research interest. The innovation of new degradable polymers for biomedical applications is challenging due to strict demands including nontoxicity of polymers and degraded products, complete degradation to avoid polymer residues in the body, and other suitable properties. Here, we demonstrate a series of degradable polymers for sustained-release drug applications synthesized by the alternating copolymerization of cyclic anhydrides and Schiff bases. In addition to common feedstocks, the copolymerization is versatile and catalyst-free, affording polymers incorporating cyclic topologies and in-chain ester and peptoid groups. Particularly, the polymers exhibit self- and autodegradation without any trigger, which is distinct from remaining degradation mechanisms. The degradation performance is widely regulated by the polymer structure and external temperature, resulting in complete degradation from a few hours to several months. Owing to their unique properties, the polymers are approved for biomedical applications, as revealed soundly through cell viability assay, in vitro and in vivo drug release.

On-body batteries with hydrogel electrolytes are a pivotal enabling technology to drive bioelectronics for healthcare and sports, yet they are prone to failure due to dynamic interfacial interference, accompanied by e-waste production. Here, dynamic imine chemistry is proposed to design on-electrode paintable biogel electrolytes that feature temperature-controlled reversible phase transition (gelling within 1.5 min) and ultrafast self-healing capability (6 s), establishing a dynamically self-adaptive interface on cyclically deforming electrodes for shielding on-body Zn-ion batteries from interfacial interference. Consequently, the deformed Zn anode shows an exceptional cycling stability of 400 h regardless of the bending radius, and the as-assembled Zn–I₂ battery delivers sufficient durability to endure 5000 deformation cycles, together extending to 1300 h and 15 000 deformation cycles via dynamically restarting the interfacial electric field, respectively. Also, the features of recyclability, biodegradation, and biocompatibility make the proposed on-body Zn–I₂ batteries appealing in terms of sustainability and biosafety, enabling their successful power supply of heart rate monitors in sports. This work demonstrates the promise of dynamic biogel chemistry for green and biorelated energy-storage systems.

The reduction of abundant benzene rings to scarce C(sp³)-rich motifs is invaluable for drug design, as C(sp³) content is known to correlate with clinical success. Cyclohexenes are attractive targets, as they can be rapidly elaborated into large product libraries and are stable against rearomatization. However, partial reduction reactions of benzenes to cyclohexenes are rare and have a very narrow scope. Herein we report a broadly applicable method that converts electron-poor benzenes to cyclohexenes and tolerates Lewis-basic functional groups such as triazoles and thioethers as well as reducible groups such as cyanides, alkynes, and sulfones. The reaction utilizes an organic donor that induces mild arene reduction by preassociation to a photoexcitable electron donor–acceptor (EDA) complex and mild isomerization of redox-inert 1,4-cyclohexadienes to reducible 1,3-cyclohexadienes without a strong base in its oxidized thioquinone methide form.

Arylative dearomatization forms quaternary stereocenters in cyclic systems with the concomitant introduction of an aromatic ring. Pd-catalyzed arylative dearomatization, which uses conditions analogous to cross-coupling, has emerged as a powerful method in an intramolecular context. But translating this from intramolecular cyclizations to an intermolecular process has proven extremely challenging: examples are scarce, and those that exist have not been rendered enantioselective, despite the potential for broad application in medicinal chemistry and natural product synthesis. We describe a strategy that utilizes attractive interactions between the ligand and substrate to overcome this challenge and promote intermolecular, highly enantioselective arylative dearomatization of naphthols using a broad range of aryl bromide electrophiles. Crucial to success is the use of the readily accessed sulfonated chiral phosphine sSPhos, which we believe engages in attractive electrostatic interactions with the substrate. Not only does sSPhos control enantioselectivity but it also drastically accelerates the reaction, most likely by facilitating the challenging palladation step that initiates dearomatization.

Metal and acid sites are two of the most crucial catalytically active components in heterogeneous catalysis. While variations in the size, morphology, and heterogeneity of metal species, or the manipulation of the strength, location, and density of acid sites, could significantly impact the catalytic performance, the combination and interplay between these sites are even more critical and have been a recent research focus. To achieve highly efficient and selective synergistic catalysis, it is desired to design a catalyst capable of orchestrating the sequential transformation of all reactants and intermediates at different active sites. In this study, we demonstrate that both acid and metal (Pd) sites can be introduced onto a nanodiamond@graphene (NDG) support particle through simple air oxidation and metal salt deposition-precipitation methods, respectively. The presence and assembly of these two catalytically active sites significantly alter the reaction network for the cyclohexanol conversion reaction. Under this strategy, the selectivity toward designated products─cyclohexene, phenol, and benzene─can be precisely tuned by the presence and patterning of these two sites on the nanodiamond particles. Specifically, we show that the catalyst with both acid sites and Pd ensemble sites, i.e., Pd/NDG, can efficiently convert cyclohexanol through consecutive dehydration and dehydrogenation reactions to form benzene with high selectivity (>80%). These findings underscore the potential of integrating metal and acid sites to design advanced catalysts with tailored reactivity and selectivity, paving the way for more efficient and versatile catalytic processes in industrial applications.

Intercalation reactions are highly dependent on the electronic and structural relationships between host and guest materials. It is difficult for divalent ions, such as Mg, to undergo intercalation reactions compared with monovalent cations. However, further development of synthetic techniques for controlling divalent ions is strongly demanded to advance applied chemistry and fundamental physics. In this study, the cointercalation of Mg and H into the transition-metal chalcogenide TaS₂ was utilized to obtain bulk polycrystalline Mg_xH_yTaS₂. Introduced H can be extracted via postannealing at approximately 400 °C without altering the crystal structure. This study clarified the relationship between superconducting properties and electronic carrier density from the perspectives of calculations and experiments, along with the advantages of using hydride as a multivalent intercalation reaction.

The high percentage of sp³-hybridized carbons and the presence of chiral carbon centers could contribute to increased molecular complexity, enhancing the likelihood of clinical success of drug candidates. Three-dimensional (3D) bridged motifs have recently garnered significant interest in medicinal chemistry. Bicyclo[2.1.1]hexanes (BCHs) are emerging 3D benzene bioisosteres, but the synthesis of chiral, highly substituted BCHs has been underexplored. Herein, we disclose the Lewis acid-catalyzed asymmetric intermolecular [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with coumarins, 2-pyrone, or chromenes to access diverse enantioenriched 1,2,3,4-tetrasubstituted BCHs bearing vicinal tertiary-quaternary stereocenters. The key to success is the introduction of chiral bisoxazoline ligands to effectively suppress the side reactions, inhibit significant racemic background reactions, and fine-tune the reactivity and regio-, enantio-, and diastereoselectivities of the reactions. The resulting BCHs hold significant potential as benzene bioisosteres in the synthesis of chiral BCHex-Sonidegib and BCHex-BMS-202, mimicking the anticancer drug Sonidegib and the PD-1/PD-L1 inhibitor BMS-202, respectively. The outcome highlights the positive impact of bioisosteric replacement on physicochemical properties, while maintaining comparable antitumor activity to their aryl-containing counterparts.

By rearranging hydrogen bond donor and acceptor groups within a standard Watson–Crick geometry, DNA can add eight independently replicable nucleotides forming four additional not found in standard Terran DNA. For many applications, the orthogonal pairing of standard and nonstandard pairs offers a key advantage. However, other applications require standard and nonstandard nucleotides to communicate with each other. This is especially true when seeking to recruit high-throughput instruments (e.g., Illumina), designed to sequence standard 4-nucleotide DNA, to sequence DNA that includes added nucleotides. For this purpose, PCR workflows are needed to replace nonstandard nucleotides in (for example) a 6-letter DNA sequence by defined mixtures of standard nucleotides built from 4 nucleotides. High-throughput sequencing can then report the sequences of those mixtures to bioinformatic alignment tools, which infer the original 6-nucleotide sequence by analysis of the mixtures. Unfortunately, the intrinsic orthogonality of standard and nonstandard nucleotides often demand polymerases that violate pairing biophysics to do this replacement, leading to inefficiencies in this “transliteration” process. Thus, laboratory in vitro evolution (LIVE) using “anthropogenic evolvable genetic information systems” (AEGIS), an important “consumer” of new sequencing tools, has been slow to be democratized; robust sequencing is needed to identify the AegisBodies and AegisZymes that AEGIS-LIVE delivers. This work introduces a new way to connect synthetic and standard molecular biology: biversal nucleotides. In an example presented here, a pyrimidine analogue (pyridine-2-one, y) pairs with Watson–Crick geometry to both a nonstandard base (2-amino-8-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one, P, the Watson–Crick partner of 6-amino-5-nitro-[1H]-pyridin-2-one, Z) and a base that completes the Watson–Crick hydrogen bond pattern (2-amino-2′-deoxyadenosine, amA). PCR amplification of GACTZP DNA with dyTP delivers products where Z:P pairs are cleanly transliterated to A:T pairs. In parallel, PCR of the same GACTZP sample at higher pH delivers products where Z:P pairs are cleanly transliterated to C:G pairs. By allowing robust sequencing of 6-letter GACTZP DNA, this workflow will help democratize AEGIS-LIVE. Further, other implementations of the biversal concept can enable communication across and between standard DNA and synthetic DNA more generally.

Catalytic asymmetric α-alkylation of simple carboxylic acid derivatives is a challenging issue due to the difficulties in achieving high catalytic efficiency and controlling the enantioselectivity. Herein, by using a copper(I)-(R)-DTBM-SEGPHOS complex as a catalyst and 2-acylimidazoles as pronucleophiles, a general method for the catalytic asymmetric α-alkylation of simple carboxylic acid derivatives is accomplished. Various alkyl electrophiles, including allyl bromides, benzyl bromides, propargyl bromide, and unactivated alkyl sulfonates, serve as efficient alkylation reagents. The reaction enjoys the advantages of an easy reaction protocol, good functional group tolerance, and high enantioselectivity. 2,4,6-Trimethylphenol is found as an effective additive to increase yields. Preliminary ¹H NMR experiments indicate the precoordination of 2-acylimidazoles to a copper(I) catalyst, which might acidify the α-hydrogens of 2-acylimidazoles and allow facile generation of stabilized copper(I) enolates. Finally, the synthetic utility of the present method is demonstrated by the asymmetric formal synthesis of AZD2716, a potent secreted phospholipase A₂ inhibitor.

A relatively unexplored energy source in synthetic cells is transmembrane electron transport, which like proton and ion transport can be light driven. Here, synthetic cells, called nanoreactors, are engineered for compartmentalized, semiartificial photosynthetic H₂ production by a Clostridium beijerinckii [FeFe]-hydrogenase (H₂ase). Transmembrane electron transfer into the nanoreactor was enabled by MtrCAB, a multiheme transmembrane protein from Shewanella oneidensis MR-1. On illumination, graphitic nitrogen-doped carbon dots (g-N-CDs) outside the nanoreactor generated and delivered photoenergized electrons to MtrCAB, which transferred these electrons to encapsulated H₂ase without requiring redox mediators. Compartmentalized, light-driven H₂ production was observed with a turnover frequency (TOF_H2ase) of 467 ± 64 h^–1 determined in the first 2 h. Addition of the redox mediator methyl viologen (MV) increased TOF_H2ase to 880 ± 154 h^–1. We hypothesize that the energetically “uphill” electron transfer step from MtrCAB to H₂ase ultimately limits the catalytic rate. These nanoreactors provide a scaffold to compartmentalize redox half reactions in semiartificial photosynthesis and inform on the engineering of nanoparticle–microbe hybrid systems for solar-to-chemical conversion.

As a representative active ingredient of traditional Chinese medicine (TCM) and a clinically approved anticancer drug, elemene (ELE) exhibits exciting potential in the antitumor field; however, appropriate drug formulations still need to be explored for specific diseases such as postoperative cancer recurrence and metastasis. Herein, we report an ELE hydrogel with controlled drug release kinetics that can allow ELE to maintain effective concentrations at local lesion sites for extended periods to enhance the bioavailability of ELE. Concretely, dopamine-conjugated hyaluronic acid is synthesized and utilized to prepare ELE nanodrug-embedded hydrogels. In a model of postoperative breast cancer recurrence and metastasis, the ELE hydrogel demonstrates a 96% inhibition rate of recurrence; in contrast, the free ELE nanodrug shows only a 65.5% inhibition rate of recurrence. Importantly, the ELE hydrogel markedly stimulates a potent antitumor immune response in the microenvironment of cancer lesions, increasing antitumor immune cells such as CD8⁺ T cells, CD4⁺ T cells, and M1-type macrophages, as well as elevating antitumor cytokines including TNF-α, IFN-γ, and IL-6. Overall, this study not only advances the field of TCM but also highlights the transformative impact of controlled-release hydrogels in improving antitumor therapy.

Semiconductors with large energetic separation ΔE^± of energy sub-bands with distinct spin expectation values (spin textures) represent a key target to enable control over spin transport and spin-optoelectronic properties. While the paradigmatic case of symmetry-dictated Rashba spin splitting and associated spin textures remains the most explored pathway toward designing future spin-transport-based quantum information technologies, controlling spin physics beyond the Rashba paradigm by accessing strategically targeted crystalline symmetries holds significant promise. In this paper, we show how breaking the traditional paradigm of octahedron-rotation based structure distortions in 2D organic–inorganic perovskites (2D-OIPs) can facilitate exceptionally large spin splittings (ΔE^± > 400 meV) and spin textures with extremely short spin helix lengths (l_PSH ∼ 5 nm). A simple bond angle difference captures the distortion-driven global asymmetry and correlates quantitatively with first-principles computed spin-splitting magnitudes. A multiband effective mass model that accounts for interlayer coupling provides a unified understanding of how specific symmetry elements dictate layer- and state-dependent spin polarizations within these multi-quantum-well structures. The general symmetry analysis methodology presented here, together with the potential for rationally creating 2D-OIPs with unique symmetry patterns, opens a pathway to design semiconductors with outstanding spin properties for next generation opto-spintronics.

Herein, we report reversible electrocatalytic NAD⁺/NADH interconversion mediated by [Cp*Ir(pyza)Cl] (1, pyza = pyrazine amidate). 1 was designed through a rational approach aimed at lowering the overpotential of NAD⁺ to NADH reduction with respect to that observed for electrocatalyst [Cp*Ir(pica)Cl] (2, pica = picolinamidate). The peculiar properties of pyza, which is substantially less σ electron-donator and more π electron-acceptor than pica, resulted in an easier bielectronic reduction process occurring at −0.29 V (instead of ca. −0.65 V for 2), very close to the equilibrium potential of NAD⁺/NADH redox couple (E°_eq = −0.32 V vs NHE, 298 K, pH 7). 1 catalyzes both NAD⁺ reduction and NADH oxidation in response to even a small departure from equilibrium potential, with a catalytic bias for the former (|i_p^red/i_p^ox| = 6.2, 333 K). The reversibility of NAD⁺/NADH interconversion was ascertained by ¹H EXSY NMR spectroscopy that clearly demonstrated the rapid establishment of 1_H + NAD⁺ ⇌ 1 + NADH equilibrium (K_eq = 3, ΔG = −0.6 kcal/mol, 298 K) and a similar hydridicity of NADH (28.9 kcal/mol, 298 K) and 1_H (28.3 kcal/mol, 298 K).

One grand challenge for deploying porous carbons with embedded metal–nitrogen–carbon (M–N–C) moieties as platinum group metal (PGM)-free electrocatalysts in proton-exchange membrane fuel cells is their fast degradation and inferior activity. Here, we report the modulation of the local environment at Fe–N₄ sites via the application of atomic Sn–N_x sites for simultaneously improved durability and activity. We discovered that Sn–N_x sites not only promote the formation of the more stable D2 FeN₄C₁₀ sites but also invoke a unique D3 SnN_x–Fe^IIN₄ site that is characterized by having atomically dispersed bridged Sn–N_x and Fe–N₄. This new D3 site exhibits significantly improved stability against demetalation and several times higher turnover frequency for the oxygen reduction reaction (ORR) due to the shift of the reaction pathway from a single-site associative mechanism to a dual-site dissociative mechanism with the adjacent Sn site facilitating a lower overpotential cleavage of the O–O bond. This mechanism bypasses the formation of the otherwise inevitable intermediate that is responsible for demetalation, where two hydroxyl intermediates bind to one Fe site. As a result, a mesoporous Fe/Sn-PNC catalyst exhibits a positively shifted ORR half-wave potential and more than 50% lower peroxide formation. This, in combination with the stable D3 site and enriched D2 Fe sites, significantly enhanced the catalyst’s durability as demonstrated in membrane electrode assemblies using complementary accelerated durability testing protocols.

Glioblastoma, a highly aggressive brain tumor, lacks effective treatment with low 5 year survival rates. Urgency for new therapies is evident. Mammalian targets of rapamycin (mTOR) and G1 to S phase transition 1 gene (GSPT1) are overexpressed in glioblastoma, regulating vital cellular functions. Current mTOR inhibitors face challenges in clinical efficacy and drug resistance. Similarly, GSPT1-targeting therapies have not progressed of glioblastoma in clinical trials. Research studies suggested that combining mTOR inhibition with GSPT1 degradation may overcome resistance and enhance efficacy. We propose the concept of jointly implementing inhibition and degradation on different proteins, integrating the properties of inhibitors and degraders into the same molecule. Introducing YB-3–17, a novel bifunctional molecule, robustly inhibits mTOR and selectively degrades GSPT1. As a tool compound for proof-of-concept studies, YB-3–17 sharpens selectivity, avoiding off-target effects, and selectively induces GSPT1 degradation and mTOR inhibition, showing superior efficacy in tumor cell lines compared to that of standalone therapies. RNA-seq analysis highlights the advantages of YB-3-17 over mTOR inhibitor treatment. YB-3–17 can safely and effectively inhibit tumor growth in mice, offering a promising direction for precision treatment of glioblastoma, representing the first attempt to combine mTOR inhibition with GSPT1 degradation. This work also demonstrates that it is conceptually possible to successfully combine the properties of small molecule inhibitors and degraders into a single molecule, killing two birds with one stone.

New polymers, properly designed for end-of-life and efficiently formed from renewable carbon, are key to the transition to a more sustainable circular plastics economy. Ring-opening polymerization (ROP) of bicyclic lactones is a promising method for the production of intrinsically recyclable polyesters, but most lactone monomers lack an efficient synthesis route from biobased starting materials, even though this is essential to sustainably account for material loss during the life cycle. Herein, we present the exceptionally rapid and controlled polymerization of a fully biobased tricyclic oxanorbornene-fused γ-butyrolactone monomer (M1). Polyester P(M1) was formed in low dispersity (D̵ = 1.2–1.3) and controllable molecular weight up to M_n = 76.8 kg mol^–1 and exhibits a high glass transition temperature (T_g = 120 °C). The orthogonal olefin and lactone functionalities offer access to a wide range of promising materials, as showcased by postpolymerization modification by hydrogenation of the olefin, which increased polymer thermal stability by over 100 °C. Next to rapid hydrolytic degradation and solvolysis, the poly(oxanorbornene-fused γ-butyrolactone) could be cleanly chemically recycled back to the monomer (CRM), in line with its favorable ceiling temperature (T_c) of 73 °C. The density functional theory (DFT)-computed ΔH° of ring-opening with methanol of γ-butyrolactone-based monomers provided a model to predict T_c, and the DFT-computed and X-ray crystal structure-derived structural parameters of M1, hydrogenated analogue M1-H₂, and regioisomer M2 offered insights into the structural descriptors that cause the high polymerizability of M1, which is key to establishing structure–property relations.

The structural characterization of new materials often poses immense challenges, especially when obtaining single-crystal structures is difficult, which is a common difficulty with covalent organic frameworks (COFs). Despite this, understanding the atomic structure is crucial as it provides insights into the arrangement and connectivity of organic building blocks, offering the opportunity to establish the correlation of structure–function relationships and unravel material properties. In this study, we present an approach for determining the structures of COFs, an integration of electron crystallography and computational intelligence (COF+). By applying established chemistry knowledge and employing particle swarm optimization (PSO) for trial structure generation, we overcome existing limitations, thus paving the way for advancements in COF structural determination. We have successfully implemented this technique on four representative COFs, each with unique characteristics. These examples underline the accuracy and efficacy of our approach in addressing the challenges tied to COF structural determination. Furthermore, our approach has revealed new structure candidates with different topologies or interpenetrations that are chemically feasible. This discovery demonstrates the capability of our algorithm in constructing trial COF structures without being influenced by topological factors. Our new approach to COF structure determination represents a significant advancement in the field and opens new avenues for exploring the properties and applications of COF materials.

Thermal energy has been considered the exclusive driving force in thermochemical catalysis, yet associated lattice expansion effects have been overlooked. To shed new light on this issue, variable temperature in situ high-resolution (scanning) transmission electron microscopy (HR-(S)TEM) and electron energy-loss spectroscopy (EELS) were employed to provide detailed information on the structural changes of an archetype nanoscale indium oxide materials and how these effects are manifest in reverse water gas shift heterogeneous catalytic reactivity. It is found that with increasing temperature and vacuum conditions, an irreversible surface lattice expansion is traced to the formation and migration of oxygen vacancies. Together, these changes are believed to be responsible for the decreased activation energy and improved reaction rate observed for the reverse water gas shift reaction. Studies of this kind provide new insight into how thermal energy affects thermochemical heterogeneous catalysis.

Due to the high demand and the increasing production rate of plastic materials, vast amounts of wastes are generated every year. An important fraction of these wastes contain polystyrene (PS), which is seldom recycled, neither mechanically nor chemically. While several chemical recycling strategies have been developed, they are either very energy-demanding or produce chemicals that can hardly be employed in the synthesis of plastics (e.g., benzene and benzoic acid). Here, we report the upcycling of PS waste into aromatic polyacids, useful in polyester synthesis, such as polyethylene terephthalate (PET). To this end, a conventional Friedel–Crafts acylation was first investigated, to produce an acylated PS chain, using acetic anhydride and stoichiometric amounts of AlCl₃. As a catalytic alternative, the alkylation of PS was studied, using InCl₃ and isopropyl acetate. The acylated and alkylated PS samples were then oxidized to produce terephthalic (TA), isophthalic (IPTA), benzoic (BA), and trimesic (TMA) acid.

Nanozyme catalytic therapeutic efficacy is limited by the finite enzyme activity and specificity. In this work, nitrogen-doped carbon loaded with a cerium single-atom nanozyme (Ce SAs@NC) is synthesized, exhibiting tumor specificity and excellent multiple enzyme-like activities. Compared with nitrogen-doped carbon loaded with CeO₂ nanoparticles, Ce SAs@NC shows excellent peroxidase-like and catalase-like activity. Ce SAs@NC can convert intracellular hydrogen peroxide into cytotoxic hydroxyl radical and O₂, which can be further transferred to superoxide radicals. Cascade enzyme reactions not only alleviate the hypoxic microenvironment of tumors but also induce lipid peroxidation and apoptosis or necrosis of tumor cells. The mild photothermal action will enhance the enzyme-like activities of Ce SAs@NC rather than induce the production of heat shock proteins to protect tumor cells. In addition, Ce SAs@NC can regulate the immune environment, stimulate M1 macrophages to trigger immune responses, and inhibit tumor proliferation. Thanks to the combination of the size effect of the single atoms, photothermal influence, multiple enzyme-like activities, and immunological effect, the Ce SAs@NC platform appears to have tumor specificity, less toxic side effects, and a high curative effect both in vitro and in vivo.

Despite the extensive studies on the adsorption and activation of hydrogen over metal oxides, it remains a challenge to investigate the structure-dependent activation of hydrogen and its selectivity mechanism in hydrogenation reactions. Herein we take spinel and solid solution MnGaO_x with a similar bulk chemical composition and study the hydrogen activation mechanism and reactivity in syngas conversion. The results show that MnGaO_x-Solid Solution (MnGaO_x-SS) is a typical Mn-doped hexagonal close-packed (HCP) Ga₂O₃ with a Ga-rich surface. Upon exposure to hydrogen, Ga–H and O–H species are simultaneously generated. Ga–H species are highly active but unselective in CO activation, forming CH_xO, and ethylene hydrogenation, forming ethane. In contrast, MnGaO_x-Spinel is a face-centered-cubic (FCC) spinel phase featuring a Mn-rich surface, thus effectively suppressing the formation of Ga–H species. Interestingly, only part of the O–H species are active for CO activation while the O–H species are inert for olefin hydrogenation over MnGaO_x-Spinel. Therefore, MnGaO_x-Spinel exhibits a higher activity and higher light-olefin selectivity than MnGaO_x-SS in combination with SAPO-18 during syngas conversion. These fundamental understandings are essential to guide the design and further optimization of metal oxide catalysts for selectivity control in hydrogenations.

Euphorbialoid A (1) belongs to the rare diterpenoid family of premyrsinanes and exhibits potent anti-inflammatory effects. The 5/7/6/3-membered carbocycle (ABCD-ring) of 1 contains 11 contiguous stereocenters and seven oxygen-containing functional groups. Moreover, four of the six hydroxy groups of 1 are concentrated in the southern sector and flanked by four structurally different acyl groups. The dense array of various functional groups with disparate reactivities on the tetracyclic ABCD-ring presents a daunting challenge for the chemical synthesis of 1. As a reflection of its formidable complexity, synthesis of 1 or any other premyrsinane diterpenoids has not yet been reported. Here, we devised a novel strategy comprising two stages and achieved the first total synthesis of 1 (35 steps as the longest linear sequence). In the first stage, the ABCD-ring was expeditiously assembled by integrating three powerful transformations: (1) Pt-doped TiO₂-catalyzed radical coupling to attach a northern chain to a 6/3-membered CD-ring, (2) Pd-catalyzed decarboxylative asymmetric allylation to construct a quaternary carbon with a southern chain, and (3) a Co-mediated Pauson–Khand reaction to cyclize the two chains into the 5/7-membered AB-ring. In the second stage, three-dimensional structures of the ABCD-ring intermediates were utilized to stereoselectively fabricate the A-ring and site-selectively append the four different acyl groups. In the present total synthesis, we revealed the significance of orchestrating the multistep reaction sequence and incorporating cyclic protective groups. The overall strategy and tactics provide new insights into designing synthetic routes to premyrsinanes and densely oxygenated terpenoids decorated with diverse acyl groups.

Constructing fibril morphology has been believed to be an effective method of achieving efficient exciton dissociation and charge transport in organic solar cells (OSCs). Despite emerging endeavors on the fibrillization of organic semiconductors via chemical structural design or physical manipulation, tuning of the fibril geometry, i.e., width and length, for tailored optoelectronic properties remains to be studied in depth. In this work, a series of alkoxythiophene additives featuring varied alkyl side chains connected to thiophene are designed to modulate the growth of fibril aggregates in cutting-edge polymer donors PM6 and D18. Molecular dynamics simulations and morphological characterizations reveal that these additives preferentially locate near and entangle with the side chains of polymer donors, which enhance the conjugated backbone stacking of polymer donors to form nanofibrils with the width expanding from 12.6 to 21.8 nm and the length increasing from 98.3 to 232.7 nm. This nanofibril structure is feasible to acquire efficient exciton dissociation and charge transport simultaneously. By integrating the fibril PM6 and L8-BO as the donor and acceptor layers in pseudo-bulk heterojunction (p-BHJ) OSCs via layer-by-layer deposition, an improvement of power conversion efficiency (PCE) from 18.7% to 19.8% is observed, contributed by enhanced light absorption, charge transport, and reduced charge recombination. The versatility of these additives is also verified in D18:L8-BO OSCs, with enhanced PCE from 19.3% to 20.1%, which is among the highest values reported for OSCs.

Metal–organic cages and capsules exhibit space-specific functions based on their discrete hollow structures. To acquire enzyme-like asymmetric or intricate structures, they have been modified by desymmetrization with two or more different ligands. There is a need to establish new strategies that can desymmetrize structures in a simple way using only one type of ligand, which is different from the mixed-ligand approach. In this study, a strategy was developed to form interconvertible stereoisomers using the unsymmetric macrocyclic ligand benzimidazole[3]arene. Single-crystal X-ray diffraction analysis revealed that the isomers assembled with silver tetrafluoroborate afforded a conformationally heteroleptic Ag₆L₄ capsule with an intricate structure. The six Ag ions in the capsule were desymmetrized, resulting in significantly different coordination geometries. Remarkably, the capsule encapsulates a single tetrafluoroborate anion via multipoint C–H···F–B hydrogen bonds in both the solid and solution states, suggesting that anions of appropriate size and shape can act as a template for the capsule formation. These results demonstrate that the use of isomerizable and unsymmetric ligands is the effectiveness of constructing highly dissymmetric supramolecular structures from a single ligand.

While latent catalysts have become a well-established strategy for locally and temporally controlling bond exchange reactions in dynamic polymer networks, there is a lack of inherently tailorable systems. Herein, we introduce a thiol–ene network based on disulfide exchange that alters its dynamic properties as a function of the color of light used during the curing reaction. For this purpose, selected allyl-bearing disulfides are synthesized, which are transparent at 450 nm but undergo disulfide scission upon 365 nm light irradiation, as confirmed by UV–vis and EPR measurements. Incorporated into a thiol–ene resin, the wavelength used in the curing reaction defines the dynamic properties of the obtained photopolymer. At 450 nm, photocuring yields a dynamic network with disulfide bonds, which relaxes to 63% of its original stress within 112 s at 160 °C (without the requirement of an external catalyst). In contrast, curing with 365 nm light induces disulfide scission yielding photopolymers, which contain predominately monosulfidic links. The permanent nature of the links effectively prevents relaxation of the polymer within a reasonable period of time, confirming the successful alteration of its dynamic properties simply by the color of the light source used.

Soft matters, particularly giant molecular self-assembly, have successfully replicated complex structures previously exclusive to metal alloys. These superlattices are constructed from mesoatoms─supramolecular spherical motifs of aggregated molecules, and the formation of superlattices critically depends on the volume distributions of these mesoatoms. Herein, we introduce two general methods to control volume asymmetry (i.e., the volumes’ ratio of the largest to smallest mesoatoms, V_L/V_S) within giant molecular self-assembly. Leveraging the spontaneous increase in the mesoatomic volume ratio in unary systems and self-sorted binary blends, we systematically adjust the volume asymmetry from 1.0 to 9.0 across 24 unary systems and 56 binary blends of giant molecules, uncovering the formation of various superlattices, including BCC, Frank-Kasper A15, σ, Laves C14, C15, NaZn₁₃, AlB₂, and notably, the first NaCl like superlattice in homogeneous soft matter self-assembly. A geometric-based analysis, combined with experimental results, further establishes a quantitative relationship between volume asymmetry and the corresponding superlattice formations, thus laying a solid foundation for superlattice engineering within giant molecular systems to mimic and even beyond metal alloys. The lattice parameters of various unit cells range from approximately 5 to 20 nm. Our investigation in giant molecules could guide the advancement of mesoscopic, periodic soft matter materials.

Due to the inherent challenges posed by the linear coordination of gold(I) complexes, asymmetric gold-catalyzed processes remain challenging, particularly in the atroposelective synthesis of axially chiral skeletons. Except for extremely few examples of intramolecular annulations, the construction of axial chirality via asymmetric gold-catalyzed intermolecular alkyne transformation is still undeveloped. Herein, a gold/HNTf₂-cocatalyzed asymmetric diazo-alkyne annulation is developed, allowing the atroposelective and divergent synthesis of chiral non-C₂-symmetric biaryls and arylquinones in generally good to excellent yield (up to 93% yield) and enantioselectivity (up to 99% ee), with broad substrate scope. Notably, this work represents the first gold-catalyzed atroposelective construction in an intermolecular manner. More interestingly, this strategy is successfully extended to the first asymmetric construction of seven-membered-ring atropisomers bearing one carbon-centered chirality in excellent diastereoselectivity and high enantioselectivity (up to 93% ee and 50:1 dr). Remarkably, the utility of this methodology is further illustrated by the successful application of a representative axially chiral ligand in a series of enantioselective reactions. Importantly, the Brønsted acid as a proton-shuttle cocatalyst significantly promotes this asymmetric annulation. Additionally, the origin of enantioselectivity of this annulation and the role of HNTf₂ are disclosed by density functional calculations and control experiments.

The revolutionary impact of photoredox catalytic processes has ignited novel avenues for exploration, empowering us to delve into nature in unprecedented ways and to pioneer innovative biotechnologies for therapy and diagnosis. However, integrating artificial photoredox catalysis into living systems presents significant challenges, primarily due to concerns over low targetability, low compatibility with complex biological environments, and the safety risks associated with photocatalyst toxicity. To address these challenges, herein, we present a novel bioorthogonally activatable photoredox catalysis approach. In this approach, potent photocatalyst selection via atom replacement of the rhodamine core yielded the bioorthogonally activatable photocatalyst (PC-Tz). The introduction of 1,2,4,5-tetrazine quenched its photocatalytic properties, which were restored upon an intracellular inverse electron-demand Diels–Alder (iEDDA) reaction with trans-cyclooctene (TCO) localized in mitochondria. This reaction led to remarkable photocatalytic oxidation of nicotinamide adenine dinucleotide (NADH), effectively manipulating the mitochondrial electron transport chain (ETC) under hypoxic conditions in cancer cells. Additionally, photocatalytic pyroptotic cell death was observed through a caspase-3/gasdermin E (GSDME) pathway, achieving notable antitumor efficacy and adenosine triphosphate (ATP) reduction in tumor cells. To the best of our knowledge, this represents the first example of bioorthogonally activatable photoredox catalysis, opening new avenues for chemists to spatiotemporally control activity in specific cell organelles without disrupting other native biological processes.

Dynamic 3D covalent organic frameworks (COFs) have shown a concerted structural transformation upon adaptive guest inclusion. However, the origin of the conformational mobility and the host–guest adaptivity remain conjecture of the pedal motions of revolving imine linkages, often without considering the steric hindrance from the interwoven frameworks. Here, we present atomic-level observation of the rotational and translational dynamics in single-crystal COF-300 upon adaptive guest inclusion of various organic molecules, featuring multiple rotamers of covalent linkages and switchable interframework noncovalent interactions. Specifically, we developed a diffusion gradient transimination protocol to facilitate the growth of COF single crystals, enabling a high-resolution X-ray diffraction structural analysis. We uncovered metastable and low-symmetry intermediate phases from contracted to expanded phases during structural evolution. We identified torsion angles in the terephthalaldehyde diimine motifs that switch from anti-periplanar to syn-periplanar/anticlinal conformations. Moreover, the rotational dynamics of the imine linkage were concurrent with the translational dynamics of tetraphenylmethane units, which tend to form the translational quadruple phenyl embrace. Such conformational mobility allows the frameworks to adapt to various guest molecules, such as alcohols, esters, phenols, and diols, featuring double linear, herringbone, zigzag chains, triple helix, and tubular alignments. Quantitative energy analyses revealed that such dynamic structure transformations are not arbitrary but follow specific pathways that resemble protein folding. The work is paving the way to developing robust, dynamic, and crystalline molecular sponges for studying the condensed structure of liquids without the need for further crystallization.

Most methods for regulating physical and chemical properties of materials involve the breaking and formation of chemical bonds, which inevitably change local structures. Two-dimensional (2D) ferromagnets are critical for spintronic memory and quantum devices, but most of them maintain ferromagnetism at low temperature, and multiaspect control of 2D ferromagnetism at room temperature or above is still missing. Here, we report a nondestructive, van der Waals (vdW) interfacial magnetochemistry strategy for above-room-temperature, multiaspect 2D ferromagnetism regulation. By vdW coupling nonmagnetic MoS₂, WSe₂, or Bi_1.5Sb_0.5Te_1.7Se_1.3 with 2D vdW ferromagnet Fe₃GaTe₂, the Curie temperature is enhanced up to 400 K, best for 2D ferromagnets, with 26.8% tuning of room-temperature perpendicular magnetic anisotropy and an unconventional anomalous Hall effect up to 340 K. These phenomena originate from changes in magnetic exchange interactions and magnetic anisotropy energy by interfacial charge transfer and spin–orbit coupling. This work opens a pathway for engineering multifunctional 2D heterostructures by vdW interfacial magnetochemistry.