ASAP (As Soon As Publishable)

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.

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.

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.

DNA photolyases use blue light and fully reduced flavin cofactor to repair UV-induced cyclobutane pyrimidine dimers (CPD) formed between two adjacent thymine bases in DNA. Thymine can form [2 + 2] cyclobutane adducts with its biological isosteres like toluene upon UV irradiation, resulting in chemically different analogues of CPD. Here, we investigated the cycloreversion reactions of two such adducts formed between thymine and toluene, T<>Tol, catalyzed by a class-I CPD photolyase. The photolyase can bind to the T<>Tol adducts efficiently and restore the constituent bases upon excitation. Using femtosecond spectroscopy, we systematically characterized all the elementary steps involved in the enzymatic cycloreversion of the T<>Tol adducts and comprehensively analyzed the key intermolecular electron-transfer (ET) reactions and cyclobutane bond splitting steps. The initial electron injection to the bound adducts happens primarily through a two-step electron hopping mechanism, unlike in CPD repair where direct electron tunneling is dominant. After electron injection and ultrafast first-bond splitting, the delicate competition between the second bond splitting and a futile back ET dictates the overall reaction quantum yields of the adducts, influenced by the stability of adduct intermediates and steric crowding around the constituent bases. The final electron return for the cycloreversion reactions adopts a different pathway compared to CPD repair. The photolyase utilizes its conserved photorepair mechanism and allows ET pathway flexibility to reverse the [2 + 2] cycloaddition reaction of non-natural analogues of CPD.

Deposits of aggregated TAR DNA-binding protein 43 (TDP-43) in the brain are associated with several neurodegenerative diseases. It is well established that binding of RNA/DNA to TDP-43 can prevent TDP-43 aggregation, but an understanding of the structure(s) and conformational dynamics of TDP-43, and TDP-43-RNA complexes, is lacking, including knowledge of how the solution environment modulates these properties. Here, we address this challenge using hydrogen–deuterium exchange-mass spectrometry. In the presence of RNA olignoucleotides, we observe protection from exchange in the RNA recognition motif (RRM) domains of TDP-43 and the linker region between the RRM domains, consistent with nucleic acid binding modulating interdomain interactions. Intriguingly, at elevated salt concentrations, the extent of protection from exchange is reduced in the RRM domains when bound to an RNA sequence derived from the 3′ UTR of the TDP-43 mRNA (CLIP34NT) compared to when bound to a (UG)6 repeat sequence. Under these conditions, CLIP34NT is no longer able to prevent TDP-43 aggregation. This suggests that a salt-induced structural rearrangement occurs when bound to this RNA, which may play a role in facilitating aggregation. Additionally, upon RNA binding, we identify differences in exchange within the short α-helical region located in the C-terminal domain (CTD) of TDP-43. These allosterically altered regions may influence the ability of TDP-43 to aggregate and fine-tune its RNA binding repertoire. Combined, these data provide additional insights into the intricate interplay between TDP-43 aggregation and RNA binding, an understanding of which is crucial for unraveling the molecular mechanisms underlying TDP-43-associated neurodegeneration.

Fatty acid de novo synthesis (FADNS) is a critical process in lipogenesis that is characteristically altered in clear cell renal cell carcinoma (ccRCC), which is the major type of kidney cancer. An important challenge in studying the FADNS process has been the accurate measurement of cytosolic lipogenic acetyl-CoA (AcCoA), the precursor in FADNS, due to its compartmentalization within cells. Here, we describe a novel NMR-based method to decode the isotopic enrichment of lipogenic AcCoA, which, as we demonstrated, is encoded in the simple signal ratios of the geminal methyl groups of lanosterol during its biosynthesis. The approach was validated based on the independence of the tracer enrichment and species along with the expected FADNS modulation using differentially enriched tracers and a well-studied drug. Application of this technique to 786-O ccRCC cells showed that glucose may serve as a major carbon source for lipogenic AcCoA in FADNS at physiological nutrient concentrations, at odds with previous studies that indicated glutamine’s dominant role through reductive carboxylation under higher nutrient conditions. Further investigation into glutamine’s alternative roles in ccRCC cells suggested its major involvement in the bioenergetic TCA cycle, pyrimidine synthesis, and glutathione synthesis, which is also critical in ccRCC growth. The glutamine-dependent glutathione synthesis was also suggested as a possible metabolic vulnerability compared to normal kidney cells using a glutathione synthesis inhibitor. The current study provides a simple tool for studying an important aspect of lipid metabolism and suggests translational implications for targeting glucose-driven lipogenesis and glutamine-supported glutathione synthesis in ccRCC.

Solid oxide ionic conductors with high ionic conductivity are highly desired for oxide-based electrochemical and energy devices, such as solid oxide fuel cells. However, achieving high ionic conductivity at low temperatures, particularly for practical out-of-plane transport applications, remains a challenge. In this study, leveraging the emergent interphase strain methodology, we achieve an exceptional low-temperature out-of-plane ionic conductivity in Na_0.5Bi_0.5TiO₃ (NBT)-MgO nanopillar-array films. This ionic conductivity (0.003 S cm^–1 at 400 °C) is over one order of magnitude higher than that of the pure NBT films and surpasses all conventional intermediate-temperature ionic conductors. Combining atomic-scale electron microscopy studies and first-principles calculations, we attribute this enhanced conductivity to the well-defined periodic alignment of NBT and MgO nanopillars, where the interphase tensile strain reaches as large as +2%. This strain expands the c-lattice and weakens the oxygen bonding, reducing oxygen vacancy formation and migration energy. Moreover, the interphase strain greatly enhances the stability of NBT up to 600 °C, well above the bulk transition temperature of 320 °C. On this basis, we clarify the oxygen migration path and establish an unambiguous strain–structure–ionic conductivity relationship. Our results demonstrate new possibilities for designing applicable high-performance ionic conductors through strain engineering.

Tetraphenylethylene (TPE) is a prototype aggregate-induced emission molecule. TPE-based conjugated macrocycles exhibit unique optical properties due to their peculiar cyclic topology. Because the symmetry of macrocycles strongly affects their photophysical properties, here we report a single-molecule study of the structures and orbitals of two TPE-based macrocycles of (C₂₆H₁₈)₄ and (C₂₆H₁₈)₆. Using scanning tunneling microscopy and spectroscopy, we discover that both macrocycles undergo spontaneous symmetry breaking in their conformations and frontier orbitals. The computational analyses reveal that the symmetry breaking is driven by a subtle interplay of higher extended conjugation between phenyl and node carbon atoms and conformation flexibility of the macrocycles. The observed symmetry breaking in TPE-based macrocycles is expected to strongly alter their photophysical properties.

Poly(ethylene oxide) (PEO)-based solid-state lithium–sulfur batteries (SSLSBs) have garnered considerable interest owing to their impressive energy density and high safety. However, the dissolved lithium polysulfide (LiPS) together with sluggish reaction kinetics disrupts the electrolyte network, bringing about ionic conductive breakpoints and severely limiting battery performance. To cure this, we propose an in situ welding strategy by introducing phosphorus pentasulfide (P₂S₅) as the welding filler into PEO-based solid cathodes. P₂S₅ can react with LiPS to form ion-conducting lithium polysulfidophosphate (LSPS), which suppresses the interaction with PEO and in situ weld breakpoints within the ionic conductive network. Of interest, LSPS also shows another function, that is, to catalyze sulfur redox reactions by decreasing the activation energy of sulfur reduction reaction from 0.87 to 0.75 eV, mitigating the shuttle effect. The in situ welding strategy helps the assembled SSLSB to feature exceptional cycling stability and a high energy density of up to 358 Wh·kg^–1 due to the high sulfur utilization. Our findings pave an avenue for practical high-performance SSLSBs with a novel welding filler for in situ welding of ionic conductive network.

The crystallization of organic polymers is often hindered by chiral units, hence resulting in chiral organic polymers typically existing as amorphous or partially crystalline phases such as natural rubber and cellulose. Similarly, as an emerging crystalline chiral polymer, chiral covalent organic frameworks (COFs) also inevitably face a delicate balance between chiral units and crystallization, limiting their production and applications in separation, catalysis, and optics. Here, we present a general strategy for producing a series of conformational chiral COFs with high crystallinity through breaking the meso conformation of achiral COFs. Conformational chirality of COF-300 was constructed by involving chiral amino-acid derivative templates during synthesis and was proven to have excellent thermodynamic (200 °C annealing in air) and dynamic stability (61% cell volume change). The stereochemistry of the conformational chiral crystals can be controllably tuned by chiral templates, resulting in wide-range circular dichroism signals from ultraviolet to infrared wavelengths and absorption dissymmetry factors (g_abs) varying by up to 300%, with a maximum of g_abs = 0.012. This strategy paves the way for stereochemistry modification, property enhancement, and exploration of new applications of crystalline chiral materials.

Discrete molecular organometallic europium(II) complexes are promising functional materials due to their ability to behave as highly sensitive band-shift luminescence thermometers. Furthering our understanding of the design principles salient to the emission behavior of such systems is important for developing them in this emerging application. To this end, a series of pseudo-C_4v-symmetric organometallic europium(II) complexes bearing systematically varying ligand sets were synthesized and characterized to probe the influence of subtle structural modification on their optical properties. Opto-structural correlation analyses via variable-temperature single-crystal X-ray diffraction and photoluminescence spectroscopy reveal a remarkable variability in properties among structurally similar complexes and a convoluted dependence of the emission characteristics on the stereoelectronic properties of the ligands. A few factors of particular influence are nevertheless identified, including the distance between the europium(II) ion and the basal plane of the square-pyramidal coordination polyhedron, the presence of pendant electron density that might further interact with the excited-state 5d orbitals, and, qualitatively, the metal–ligand flexibility of the construct. These results help to elucidate principles that govern the luminescence properties of organometallic europium(II) complexes with an eye to enabling the rational design of high-performance luminescence thermometers of this genre.

Accurate quantification of cisplatin (cDDP) in body fluids (blood, urine, and ascites) is crucial in monitoring therapeutic processes, assessing drug metabolism, and optimizing treatment schedules for cancer patients. Nonetheless, due to the inherent fluorescence and complexity of the body fluid matrix, along with the low cDDP concentrations in these fluids during treatment, using fluorescent sensors for fluid detection remains a subject of ongoing research. Herein, a series of water-soluble cDDP-activatable fluorescent sensors was rationally constructed by introducing thioether groups to the xanthene skeleton based on the chalcogenophilicity of platinum. These sensors exhibit excellent sensitivity and certain anti-interference capabilities for sensing cDDP in living cells, rat tissues, and zebrafish. Especially, with a simplified sample pretreatment procedure, for the first time, Rh3 and Rh4 have enabled quantitative detection of cDDP levels in diversiform body fluids from clinical ovarian and bladder cancer patients. These results are highly consistent with those obtained by ICP-MS detection. This work paves the way for utilizing fluorescent sensors in clinical body fluid analysis, thus potentially revolutionizing the monitoring methods of cDDP in clinic settings.

Proteolysis targeting chimera (PROTAC) degraders are typically bifunctional with one E3 ligase ligand connected to one target protein ligand via a linker. While augmented valency has been shown with trivalent PROTACs targeting two binding sites within a given target protein, or used to recruit two different targets, the possibility of recruiting two different E3 ligases within the same compound has not been demonstrated. Here we present dual-ligase recruitment as a strategy to enhance targeted protein degradation. We designed heterotrivalent PROTACs composed of CRBN, VHL and BET targeting ligands, separately tethered via a branched trifunctional linker. Structure–activity relationships of 12 analogues qualifies AB3067 as the most potent and fastest degrader of BET proteins, with minimal E3 ligase cross-degradation. Comparative kinetic analyses in wild-type and ligase single and double knockout cell lines revealed that protein ubiquitination and degradation induced by AB3067 was contributed to by both CRBN and VHL in an additive fashion. We further expand the scope of the dual-ligase approach by developing a heterotrivalent CRBN/VHL-based BromoTag degrader and a tetravalent PROTAC comprising of two BET ligand moieties. In summary, we provide proof-of-concept for dual-E3 ligase recruitment as a strategy to boost degradation fitness by recruiting two E3 ligases with a single degrader molecule. This approach could potentially delay the outset of resistance mechanisms involving loss of E3 ligase functionality.

The i-motif is a pH-responsive cytosine-rich oligonucleotide sequence that forms, under acidic conditions, a quadruplex structure. This tunable structural switching has made the i-motif a useful platform for designing pH-responsive nanomaterials. Despite the widespread application of i-motif DNA constructs as biomolecular switches, the mechanism of i-motif folding on the atomic scale has yet to be established. We investigate the early folding structural dynamics of i-motif oligonucleotides with laser-pulse-induced pH-jump time-resolved X-ray solution scattering. Following the pH-jump, we observe that the initial random coil ensemble converts into a contracted intermediate state within 113 ns followed by further folding on the 10 ms time scale. We reveal the representative structures of these transient species, hitherto unknown, with molecular dynamics simulations and ensemble fitting. These results pave the way for understanding metastable conformations of i-motif folding and for benchmarking emerging theoretical models for simulating noncanonical nucleic acid structures.

Constructing circularly polarized luminescence (CPL) materials that exhibit dynamic handedness inversion and emissive color modulation for multimodal information encryption presents both a significant challenge and a compelling opportunity. Here, we have developed a pyridinethiazole acrylonitrile-cholesterol derivative (Z-PTC) that exhibits wavelength-dependent photoisomerization and photocyclization, enabling dynamic handedness inversion and emissive color modulation in supramolecular assemblies with decent CPL activity. Coordination with Ag⁺ ions form the Z-PTC Ag supramolecular polymer (SP₁), which assembles into nanotubes displaying enhanced positive yellow-green CPL. Irradiation at 454 nm transforms SP₁ into nanospheres of a mixture supramolecular polymer (SP₂) of Z/E-PTC Ag, displaying inverted supramolecular chirality and emitting negative orange-yellow CPL. Reheating SP₂ to 343 K restores the original nanotube structure via excellent reversible photoisomerization. Exposure to 365 nm light also induces CPL inversion from positive to negative and triggers morphological changes from SP₁ to SP₂. Prolonged irradiation causes further transformation into irregular supramolecular aggregate, shifting the emission color to blue and eliminating CPL. These dynamic properties of the multicolor CPL system, including reversible handedness inversion, can also be realized in the semisolid state, exhibiting promising potential for multimodal information encryption applications with enhanced security and complexity.

Developing precious metal-free catalysts for organic reactions under mild conditions is urgent. Herein, we report a three-dimensional covalent organic framework (3D-COF) with high crystallinity and permanent pores, termed 3D-TABPA-COF, for the oxidation of tetrahydroquinoline to quinoline. The 3D-TABPA-COF assembled based on N₄,N₄-bis(4′-amino-[1,1′-biphenyl]-4-yl)-[1,1′-biphenyl]-4,4′-diamine (TABPA) is the catalytic active center for the conversion of tetrahydroquinoline. The triphenylamine in the structure is an effective photosensitizer, which not only enhances the light absorption capacity but also facilitates the rapid transfer of photogenerated electrons and ensures effective carrier separation. The obtained 3D-TABPA-COF has a high specific surface area (2745.06 m² g^–1) and mesopores of 3.57 nm. This is attributed to the fact that the bor topology is not easy to interpenetrate. It can oxidize tetrahydroquinoline to obtain quinoline efficiently under visible light irradiation. In addition, we also performed various photochemical characterizations combined with density functional theory calculations to elucidate the reaction mechanism from tetrahydroquinoline to quinoline. This work provides a feasible strategy for constructing 3D-COF to achieve efficient photocatalytic organic reactions.

Traditional desalination methods face criticism due to high energy requirements and inadequate trace ion removal, whereas natural light-driven ion pumps offer superior efficiency. Current synthetic systems are constrained by short exciton lifetimes, which limit their ability to generate sufficient electric fields for effective ion pumping. We introduce an innovative approach utilizing covalent-organic framework membranes that enhance light absorption and reduce charge recombination through vertical gradient protonation of imine linkages during acid-catalyzed liquid–liquid interfacial polymerization. This technique creates intralayer and interlayer heterojunctions, facilitating interlayer hybridization and establishing a robust built-in electric field under illumination. These improvements enable the membranes to achieve remarkable ion transport across extreme concentration gradients (2000:1), with a transport rate of approximately 3.2 × 10¹² ions per second per square centimeter and reduce ion concentrations to parts per billion. This performance significantly surpasses that of conventional reverse osmosis systems, representing a major advancement in solar-powered desalination technology by substantially reducing energy consumption and secondary waste.

A mechanistic investigation into the novel combination of the pseudo-halogen effect with enantioselective aminocatalysis unravels the mechanistic intricacies of [6 + 4] and [10 + 6] higher-order cycloadditions and the succeeding new Favorskii-like rearrangements. By introducing the OTf-group into the tropone framework, it can serve both as an activator for the cycloaddition and as a proficient leaving group within the corresponding cycloadduct, thus enabling unprecedented ring-contracting Favorskii-like rearrangements. Integrating the -OTf group creates an electron-deficient 6π-component leveraging the pseudo-halogen effect by enhancing the polarization and introducing new strategic interaction points. This modification complements electron-rich 4π- and 10π-components from amino-activated 2,4-dienals or indene-carbaldehydes. A comprehensive DFT investigation supported by experimental results demonstrates that the [6 + 4] system proceeds through a rate-limiting stepwise exo-cycloaddition leading to a cycloadduct initially in a boat-conformation, subsequently transitioning to the more stable chair-conformation. The change in conformation ensures an S_N1-like expulsion of the -OTf group, generating a stable carbocation bridgehead primed for a novel Favorskii-like seven-to-six ring-contracting rearrangement, resulting in the experimentally observed product. As proof-of-concept for the cycloaddition/Favorskii-like rearrangement, it is demonstrated that this approach can be extended to an unprecedented [10 + 6] cycloaddition. In contrast to the [6 + 4] system, the [10 + 6] system distinguishes itself with a concerted S_N1-like/Favorskii-like six-to-five ring-contracting rearrangement, representing the rate-limiting step. This novel concept results in the experimental isolation of structurally complex products in high peri-, diastereo-, and enantioselectivity with moderate yield. These findings demonstrate the pseudo-halogen effect’s multifaceted role in promoting and enabling novel reactivity.

Division is crucial for replicating biological compartments and, by extension, a fundamental aspect of life. Current studies highlight the importance of simple vesicular structures in prebiotic conditions, yet the mechanisms behind their self-division remain poorly understood. Recent research suggests that environmental factors can induce phase transitions in fatty acid-based protocells, leading to vesicle fission. However, using chemical energy to induce vesicle division, similar to the extant of life, has been less explored. This study investigates a mechanism of vesicle division by membrane budding driven by chemical energy without complex molecular machinery. We demonstrate that, in response to chemical fuel, simple fatty acid-based vesicles can bud off smaller daughter vesicles. The division mechanism is finely controlled by adjusting fuel concentration, offering valuable insights into primitive cellular dynamics. We showcase the robustness of self-division across different fatty acids, retaining encapsulated materials during division and suggesting protocell-like behavior. These results underscore the potential for chemical energy to drive autonomous replication in protocell models, highlighting a plausible pathway for the emergence of life. Furthermore, this study contributes to the development of synthetic cells, enhancing our understanding of the minimal requirements for cellular life and providing a foundation for future research in synthetic biology and the origins of life.

The development of highly efficient sensors for low-concentration SO₂ at room temperature is important for human health and fine chemistry, but it still faces critical challenges. Herein, a scalable olefin-linked covalent organic framework (COF) with an ultramicroporous structure and abundant binding sites is first developed as the SO₂ sensing material. The COF can adsorb SO₂ of 220 cm³/g at 1 bar and 40 cm³/g at 0.01 bar and 298 K, surpassing all reported COFs. The computational and kinetic adsorption studies deeply unveil the selective adsorption mechanism for low-concentration SO₂. Furthermore, the multicomponent gas mixture breakthrough experiments confirm that the COF can specifically capture low-concentration (2000 ppm) SO₂. We innovated a melt polymerization technology to fabricate COF films with adjustable substrates and film thicknesses. COF films are directly grown on the interdigital electrodes to prepare the SO₂ sensor device, which possesses a low detection limit (86 ppb) and excellent selectivity for SO₂ in the presence of 10 other potentially interfering gases. Compared to other reported SO₂ sensors, its overall performance is among the top. Prominently, the sensor maintains a stable output signal for more than two months, and recovery can be easily achieved by simply purifying nitrogen at room temperature without heating. This study marks the first use of COFs for SO₂ sensing, opening new possibilities for COFs in the detection of low-concentration toxic gases and manufacturing gas sensor devices.

Potassium ion (K⁺) is the most abundant metal ion in cells and plays an indispensable role in practically all biological systems. Although there have been reports of both synthetic and genetically encoded fluorescent K⁺ indicators, there remains a need for an indicator that is genetically targetable, has high specificity for K⁺ versus Na⁺, and has a high fluorescent response in the red to far-red wavelength range. Here, we introduce a series of chemigenetic K⁺ indicators, designated as the HaloKbp1 series, based on the bacterial K⁺-binding protein (Kbp) inserted into HaloTag7 self-labeled with environmentally sensitive rhodamine derivatives. This series of high-performance indicators features high brightness in the red to far-red region, large intensiometric fluorescence changes, and a range of K_d values. We demonstrate that they are suitable for the detection of physiologically relevant K⁺ concentration changes such as those that result from the Ca²⁺-dependent activation of the BK potassium channel.

Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and has been widely applied in the industrial production of drug molecules. However, despite the great success in ATH of ketones, highly efficient, regio- and stereoselective ATH on enones remains underdeveloped. Moreover, optically pure acyloins and 1,2-diols are both extremely useful building blocks in organic synthesis, medicinal chemistry, and materials science, but concise asymmetric approaches allowing access to different types of acyloins and 1,2-diols have scarcely been discovered. We report in this paper the first highly efficient ATH of readily accessible β,γ-unsaturated α-diketones. The protocol affords four types of enantioenriched acyloins and four types of optically pure 1,2-diols in highly regio- and stereoselective fashion. The synthetic value of this work has been showcased by the divergent synthesis of four related natural products. Moreover, systematic mechanistic studies and density functional theory (DFT) calculations have illustrated the origin of the reactivity divergence, revealed the different roles of aromatic and aliphatic substituents in the substrates, and provided a range of unique mechanistic rationales that have not been disclosed in ATH-related studies.

Organic photovoltaics (OPVs) have recently shown substantial progress in enhancing device efficiency, driven in particular by advances in the design of nonfullerene acceptors and the reduction of the energy offset driving exciton separation at the donor/acceptor interface. Herein, we employ temperature-dependent transient absorption spectroscopy to investigate the activation energy for charge generation and recombination in a range of bulk heterojunction blends with nonfullerene acceptors. Remarkably, we find that in all cases charge generation is almost activationless, in the range of 11–21 meV, independent of energetic offset. Geminate recombination is also observed to be almost activationless, with only the kinetics of bimolecular charge recombination being strongly temperature-dependent, with an activation energy >400 meV. Our observation of essentially activationless charge generation, independent of energy offset, strongly indicates that charge generation in such blends does not follow Marcus theory but can rather be considered an adiabatic process associated with the motion of thermally unrelaxed carriers.

The application of perovskite oxide for high-temperature electrocatalysis is hindered by its limited activity. Exsolution is a smart strategy that allows the enrichment of the perovskite’s surface with highly reactive phases, yielding heteroboundaries. However, the identification of the exact catalytic role of this complex architecture is still elusive. Here we presented a quantitative analysis of the CO₂ electroreduction reactivity of a series of perovskite thin film platforms (La_0.4Ca_0.4Ti_0.94Ni_0.06O₃, LCTN) boosted by exsolved heteropical nanoparticles (particularly for Ni and NiO). The cross-scale electrochemical characterizations, together with density functional theory (DFT) modelings, have shown clear evidence that the boundary length of the NP/perovskite interface is strictly correlated with the CO₂RR activity. The intrinsic reaction rate per active site at the NiO/LCTN boundary demonstrates a highest turnover frequency (TOF) of 7.05 ± 0.75 × 104 s^–1 at 800 °C, which is 2.5 times and 4 orders of magnitude better than that of Ni/LCTN and LCTN, respectively. The ab initio molecular dynamics (AIMD) proves that the CO₂ absorption at the NiO/LCTN boundary leverages a bidentate carbonate modality with a reduced dissociation energy barrier. Moreover, a multifold enhancement in oxygen exchange rate was confirmed, which correlated to the facilitated oxygen ion hopping between adjacent TiO₆ octahedrons. Further near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) during CO₂ electrolysis on model electrolyzers reveals the crucial role of the NiO/LCTN boundary in stabilizing oxidized carbon intermediates, raising the onset potential threshold of adventitious carbon as well as preventing its build-up.

Two contradictory theories, Clar’s sextet and resonance theory, explain the stability of conjugated macrocycles using localized and delocalized models, respectively. To reconcile these theories and gain better insights, PAH-containing porphyrinoids were chosen as a representative class of conjugated macrocycles. Two types of Clar’s sextets were identified and proposed for the first time based on their interaction with global conjugated pathways: (i) shared sextets that integrate with and perturb the global resonance pathway, and (ii) independent sextets that are separate from the pathway and potentially stabilize or do not perturb it. To test our hypothesis, we synthesized precise regioisomers with and without an independent sextet to exclude variables such as steric hindrance, different PAH characteristics, and other elements. This task is challenging due to the extensive synthetic efforts needed for regioisomeric PAH-containing porphyrinoids. We focused on 2,3-vinylnaphthiporphyrin, which features shared sextets, because its o-regioisomers are readily accessible. Two distinct regioisomers (1,2-vinylnaphthiporphyrins) with an independent sextet were synthesized along with unexpected nonaromatic N-fused porphyrinoids. Our analysis shows that 1,2-vinylnaphthiporphyrins with an independent sextet are more aromatic than 2,3-vinylnaphthiporphyrin (nonaromatic). This sextet analysis was also applied to other reported and yet-to-be-synthesized PAH-containing porphyrinoids, and these results are consistent with our current study.

Photostriction is a phenomenon that can potentially improve the precision of light-driven actuation, the sensitivity of photodetection, and the efficiency of optical energy harvesting. However, known materials with significant photostriction are limited, and effective guidelines to discover new photostrictive materials are lacking. In this study, we perform a high-throughput computational search for new photostrictive materials based on simple thermodynamic descriptors, namely, the band gap pressure and stress coefficients. Using the Δ-SCF method based on density functional theory, we establish that these descriptors can accurately predict intrinsic photostriction in a wide range of materials. Subsequently, we screened over 4770 stable semiconductors with a band gap below 2 eV from the Materials Project database to search for strongly photostrictive materials. This search identifies Te₂I as the most promising candidate, with photostriction along out-of-plane direction exceeding 8 × 10^–5 with a moderate photocarrier concentration of 10¹⁸ cm^–3. Furthermore, we provide a detailed analysis of factors contributing to strong photostriction, including bulk moduli and band-edge orbital interactions. Our results provide physical insights into the photostriction of materials and demonstrate the effectiveness of using simple descriptors in high-throughput searches for new functional materials.

Resolving the sequence and structure of flexible biomolecules such as DNA is crucial to understanding their biological mechanisms and functions. Traditional structural biology methods remain challenging for the analysis of small and disordered biomolecules, especially those that are difficult to label or crystallize. Recent development of single-molecule tip-enhanced Raman spectroscopy (TERS) offers a label-free approach to identifying nucleobases in a single DNA chain. However, a clear demonstration of sequencing both spatially and spectrally at single-base resolution is still elusive due to the challenges caused by weak Raman signals and the flexibility of DNA molecules. Here, we report a proof-of-principle demonstration to this end, spectrally resolving in real space individual nucleobases and their sequence structures within a short, single-stranded DNA molecule artificially designed. This breakthrough is achieved through the development of subnanometer-resolved low-temperature TERS methodology for such thermally unstable flexible biomolecules. Further TERS mapping over individual nucleobases provides additional structural information about the molecular configurations and even the locations of functional groups, offering a way to track modification types and binding sites in biomolecules.

A fine-tuning of enantioselective carbene insertion into primary C(sp³)–H bonds has been realized in challenging substrates, such as N-methyl unblocked aromatic and non-deactivated aliphatic tertiary amines, in which sterically demanding β-axially chiral iridium porphyrin catalysts play a crucial role. This primary C(sp³)–H alkylation with diazo compounds affords a series of β-chiral tertiary amines in high yields with excellent enantioselectivities. Notably, the protocol was successfully applied to the postmodification of chiral bicuculline, yielding the desired derivative with high diastereoselectivity. This approach paves a facile way for the stereodivergent derivation of chiral alkaloid natural products featuring an N-methyl handle. In addition, a mechanism for the reaction was proposed based on deuterium experiments and an identified cationic iridium species via HRMS analysis.

Cytochrome bc₁ (complex III) represents a significant target for the discovery of both drugs and fungicides. Metyltetraprole (MET) is commonly classified as a quinone site inhibitor (Q_oI) that combats the G143A mutated isolate, which confers high resistance to strobilurin fungicides such as pyraclostrobin (PYR). The binding mode and antiresistance mechanism of MET remain unclear. Here, we determined the high-resolution structures of inhibitor-bound S. cerevisiae complex III (MET, 2.52 Å; PYR, 2.42 Å) and inhibitor-bound porcine complex III (MET, 2.53 Å; PYR, 2,37 Å) by cryo-electron microscopy. The distinct binding modes of MET and PYR were observed for the first time. Notably, the MET exhibited different binding modes in the two species. In S. cerevisiae, the binding site of MET was the same as PYR, serving as a Pm-type inhibitor of the Q_o site. However, in porcine, MET acted as a dual-target inhibitor of both Q_o and Q_i. Based on the structural insights, a novel inhibitor (YF23694) was discovered and demonstrated excellent fungicidal activity against downy mildew and powdery mildew fungi. This work provides a new starting point for the design of the next generation of inhibitors to overcome the resistance.

Hybrid organic–inorganic semiconductors with strong electron–phonon interactions provide a programmable platform for developing a variety of electronic, optoelectronic, and quantum materials by controlling these interactions. However, in current hybrid semiconductors such as halide perovskites, anharmonic vibrations with rapid dephasing hinder the ability to coherently manipulate phonons. Here, we report the observation of long-lived coherent phonons in lead organic chalcogenides (LOCs), a new family of hybrid two-dimensional semiconductors. These materials feature harmonic phonon dynamics despite distorted lattices, combining long phonon dephasing times with tunable semiconducting properties. A dephasing time -up to 75 ps at 10 K, with up to ∼500 cycles of phonon oscillation between scattering events, was observed, corresponding to a dimensionless harmonicity parameter that is more than an order of magnitude larger than that of halide perovskites. The phonon dephasing time is significantly influenced by anharmonicity and centrosymmetry, both of which can be tuned through the design of the organic ligands enabled by the direct bonding between the organic and inorganic motifs. This research opens new opportunities for the manipulation of electronic properties with coherent phonons in hybrid semiconductors.

The clinical translation of oligonucleotide-based therapeutics continues to encounter challenges in delivery. In this study, we introduce a novel class of delivery vehicles for oligonucleotides that are based on poly(ethylene glycol) (PEG) bottlebrush polymers with sequence-defined backbones. Using solid-phase synthesis and bespoke phosphoramidites, the oligonucleotide and the polymer backbone can be assembled on the solid support. The synthesis allows chemical modifiers such as carbon 18 (C₁₈) units to be incorporated into the backbone in specific patterns to modulate the cell–material interactions. Subsequently, PEG side chains were grafted onto the polymer segment of the resulting polymer–oligonucleotide conjugate, yielding bottlebrush polymers. We report an optimal pattern of the C₁₈ modifier that leads to improved cellular uptake, plasma pharmacokinetics, biodistribution, and antisense activity in vivo. Our results provide valuable insights into the structure–property relationship of polymer–oligonucleotide conjugates and suggest the possibility of tuning the polymer backbone to meet the specific delivery requirements of various diseases.

Although Fe–S clusters are privileged metallocofactors for the reduction of N₂, CO, and other π-acidic substrates, their constituent metal ions─high-spin Fe²⁺ and Fe³⁺─are typically not amenable to binding and activating strong π-acids. Here, we demonstrate that [Fe₄S₄]⁺ clusters can overcome this limitation by adopting a noncanonical electronic structure. Specifically, we report the synthesis and characterization of a series of 3:1 site-differentiated [Fe₄S₄]⁺ clusters in which the unique Fe site is bound by one of 10 electronically variable arylisocyanide ligands. Rather than being continuously tuned as a function of the arylisocyanides’ electronic properties (e.g., as quantified by linear free energy relationships), the structures of the clusters are divided into two groups: (i) those with moderately π-acidic isocyanides, which adopt a “typical” structure characterized by standard bond metrics and geometric distortions from tetrahedral symmetry, and (ii) those with more strongly π-acidic isocyanides, which adopt a “contracted” structure with an unusually symmetric geometry and a compressed cluster core. Computational studies revealed that although the “typical” structure has a canonical electronic structure, the “contracted” structure has a noncanonical arrangement of spin density, with a full complement of π-backbonding electrons and more substantial Fe–Fe delocalization. These features of the “contracted” structure enable substantial C≡N bond weakening of the strongest π-acceptors in the series. More generally, the experimental characterization of the “contracted” electronic isomer suggests that other noncanonical electronic structures of Fe–S clusters remain to be discovered.

Magnetic anisotropy slows down magnetic relaxation and plays a prominent role in the design of permanent magnets. Coordination compounds of Co(II) in particular exhibit large magnetic anisotropy in the presence of low-coordination environments and have been used as single-molecule magnet prototypes. However, only a limited sampling of cobalt’s vast chemical space has been performed, potentially obscuring alternative chemical routes toward large magnetic anisotropy. Here we perform a computational high-throughput exploration of Co(II)’s chemical space in search of new single-molecule magnets. We automatically assemble a diverse set of ∼15,000 novel complexes of Co(II) and fully characterize them with multireference ab initio methods. More than 100 compounds exhibit magnetic anisotropy comparable to or larger than leading known compounds. The analysis of these results shows that compounds with record-breaking magnetic anisotropy can also be achieved with coordination four or higher, going beyond the established paradigm of two-coordinated linear complexes.

Radical coupling reactions are generally known to have a low selectivity due to the high reactivity of radicals. In this study, high regio and substrate selectivity was discovered in the dimerization of triarylimidazolyl radicals (TAIR), a versatile photochromic reaction. When two different radicals, 2-(4-cyanophenyl)-4,5-diphenyl-1H-imidazolyl radical (CN-TAIR) and 2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazolyl radical (OMe-TAIR), were simultaneously generated in situ, a hexaarylbiimidazole, formed by selective coupling at the nitrogen atom at position 1 of CN-TAIR and the carbon atom at position 2 of OMe-TAIR, was isolated with high selectivity as the main product among 24 possible radical dimer hexaarylbiimidazole derivatives. This high regio and substrate selectivity cannot be explained solely by the stability of the product and/or the electrophilicity and nucleophilicity of the radicals but originates from the aromaticity of the transition state in the radical–radical coupling reaction. To date, the selectivity of radical coupling reactions has been thought to be controlled by steric hindrance and radical spin density, but this study revealed a new factor for controlling radical coupling, that is, transition-state aromaticity. Aromaticity has been reported to have an important effect not only in the reactivity and structure of ground-state molecules but also on the electronically excited states and transition states in pericyclic reactions such as the Diels–Alder reaction and the Cope–Claisen rearrangement. This study demonstrated for the first time that radical coupling reactions can also be controlled by transition-state aromaticity.

Organic photofunctional materials exhibit properties that are highly dependent on their structural hierarchy. The variability in intermolecular interactions and molecular packing in both monomeric and aggregated states complicates the controllability and predictability of their photophysical and photochemical properties. To address this challenge, we developed three luminescent supramolecular [c2]daisy chains as simplified models. The rigid and mutually embedded linkers between the host and guests facilitate the formation of [c2]daisy chains with balanced stability and dynamics. Additionally, the close and tunable π–π interactions between the luminescent units provide a structural basis for fluorescence modulation and topochemical photoreactions. We performed two sets of comparisons to assess luminescence and photoreactivity: one comparison involves molecules with and without crown ethers, and the other contrasting their behavior under UV excitation in solution (diluted and concentrated) versus in the aggregated and crystalline states. Specifically, in the crystalline state, [c2]daisy chains effectively stabilize molecular packing, leading to highly efficient dimer-dependent emission. This unique structure remains in both solution (c > 1 mM) and aggregated states, which can direct the reaction pathway toward rapid and efficient intermolecular photocycloaddition upon UV irradiation. However, in highly diluted solution (10 μM), [c2]daisy chains dissociate into monomers, which further undergo intramolecular photocyclization. This study provides new insights into employing supramolecular strategies for controllable molecular aggregation and the fine-tuning of photoreaction pathways and kinetics.

Systems chemistry has emerged as a useful paradigm to access structures and phenomena typically exhibited by living systems, including complex molecular systems such as self-replicators and foldamers. As we progress further toward the noncovalent synthesis of life-like systems, and eventually life itself, it is necessary to gain control over assembly pathways. Dissipative chemical fueling has enabled access to stable populations of (self-assembled) structures that would normally form only transiently. Here, we report a synthetic dynamic combinatorial library, made from a single structurally simple building block, from which a self-replicator and a foldamer can emerge along two distinct and competing pathways through an inter- or intramolecular assembly process, respectively. A fueled chemical reaction cycle is then set up to generate the foldamer transiently, in the presence of the self-replicator. The partitioning of the building block between the folding and self-replication pathways and the duration of the fueled reaction cycles are controlled by adjusting the amount of the chemical fuel. An out-of-equilibrium steady state involving the two assemblies could also be achieved by using a continuous stirred tank reactor with inflow and outflow of material. This work connects the domains of folding and self-replication in synthetic systems through dissipative out-of-equilibrium chemistry. It demonstrates that foldamers and self-replicators, formed from the same building block, can stably coexist if the system is continuously supplied with energy, while at equilibrium, the Gibbs phase rule prohibits such coexistence.

Self-replicating molecules and well-defined folded macromolecules are of great significance in the emergence and evolution of life. How they may interconnect and affect each other remains largely elusive. Here, we demonstrate an abiotic system where a single building block can oligomerize to yield either a self-replicating molecule or a foldamer. Specifically, agitation of a disulfide-based dynamic combinatorial library at moderately elevated pH channels it selectively into a self-replicating hexamer assembled into fibers, after passing through a period where a 15-subunit macrocyclic foldamer existed transiently. Without mechanoagitation or at lower pH, the formation of hexamer fiber is suppressed, resulting in the accumulation of the 15mer foldamer. Foldamer and self-replicator can be interconverted in response to external stimuli, including agitation and a change in pH. Furthermore, upon the addition of a photoacid, the pH of the medium can be controlled by irradiation, driving the switching between replicator and foldamer and allowing a dissipative out-of-equilibrium state to be accessed, using light as a source of energy.

Pyroglutamate is a cyclic N-terminal post-translational modification that occurs in both proteins and peptide hormones. The prevalence and biological roles of pyroglutamate are little understood, in part due to limited tools to identify, quantify, and manipulate its pyrrolidinone structure. Selective modification of pyroglutamate residues in complex polypeptides may provide unique tools to better understand its biological roles and to allow late-stage diversification of biologically active pyroglutamate-containing sequences. This work describes a copper-catalyzed N–H cross-coupling of unprotected peptides that is selective for N-terminal pyroglutamate residues. The reaction is operationally simple under mild conditions and tolerates all canonical residues. Mechanistic studies point to a key role for a multidentate copper-binding mode of the extended polypeptide structure in delivering the observed reactivity. The reaction allows for direct labeling and identification of a pyroglutamate hormone present in porcine intestinal extracts.

The presence of inherent electronic unsaturation in aluminum predominantly results in the formation of aluminum clusters, with very few examples of compounds containing discrete chains of aluminum atoms in existence. In this work, we present the successful synthesis and structural authentication of a highly unusual trialane species with a near-linear chain of three Al atoms, alongside a carbene-stabilized aluminyl anion ([LAlR₂]⁻), an alternative product produced by varying the reaction conditions. Quantum-chemical calculations have been applied to elucidate the electronic structure and bonding of these novel compounds. Additionally, we successfully trapped a reaction intermediate using an alkyne, suggesting the intermediacy of a base-stabilized monomeric alumylene (LRAl:), which is also investigated through computational methods.

The unique properties and processability of conducting and semiconducting organic materials have fascinated scientists since their discovery. Of this broad class of materials, conductive coordination polymers are of immense recent interest due to their innate modularity and tunability. However, these materials are typically generated as powders and, in some cases, single crystals which significantly limits possible processing and many applications. Herein, we report a method that enables solution-phase processing of a previously reported highly conductive coordination polymer, NiTTFtt (TTFtt = tetrathiafulvalenetetrathiolate), into thin films and conductive textiles. Thin films of NiTTFtt show record-breaking conductivity for a coordination polymer and unusual physical behavior that sheds light on the transport mechanisms in this glassy metallic material. Textiles coated with NiTTFtt are conductive and durable to air, water, washing, acid, base, and mechanical cycles. The properties and processability of NiTTFtt reported here make it notable among coordination polymers and conducting organic materials more broadly.

Transition-metal-mediated splitting of N₂ to form metal nitride complexes could constitute a key step in electrocatalytic nitrogen fixation, if these nitrides can be electrochemically reduced to ammonia under mild conditions. The envisioned nitrogen fixation cycle involves several steps: N₂ binding to form a dinuclear end-on bridging complex with appropriate electronic structure to cleave the N₂ bridge followed by proton/electron transfer to release ammonia and bind another molecule of N₂. The nitride reduction and N₂ splitting steps in this cycle have differing electronic demands that a catalyst must satisfy. Rhenium systems have had limited success in meeting these demands, and studying them offers an opportunity to learn strategies for modulating reactivity. Here, we report a rhenium system in which the pincer supporting ligand is supplemented by an isocyanide ligand that can accept electron density, facilitating reduction and enabling the protonation/reduction of the nitride to ammonia under mild electrochemical conditions. The incorporation of isocyanide raises the N–H bond dissociation free energy of the first N–H bond by 10 kcal/mol, breaking the usual compensation between pK_a and redox potential; this is attributed to the separation of the protonation site (nitride) and the reduction site (delocalized between Re and isocyanide). Ammonia evolution is accompanied by formation of a terminal N₂ complex, which can be oxidized to yield bridging N₂ complexes including a rare mixed-valent complex. These rhenium species define the steps in a synthetic cycle that converts N₂ to NH₃ through an electrochemical N₂ splitting pathway, and show the utility of a second, tunable supporting ligand for enhancing nitride reactivity.

Biomolecular condensates provide a mechanism for compartmentalization of biomolecules in eukaryotic cells. These liquid-like condensates are formed via liquid–liquid phase separation, by a plethora of interactions, and can mediate several biological processes in healthy cells. Expansions of dipeptide repeat proteins, DPRs, in which arginine rich DPRs like poly-proline-arginine (PR), and poly-glycine-arginine (GR), partition RNA into condensates can however induce cell toxicity. Here, we use (GR)₂₀ as a model for biological poly-GR and condense it using either excluded volume interactions with polyethylene glycol (PEG) as a crowder or direct electrostatic interactions with RNA oligomers. Using two-dimensional infrared (2D IR) spectroscopy, we observe that (GR)₂₀ condensed through an excluded volume forms β-sheet structures, whereas (GR)₂₀ condensed with RNA forms loops. We also investigate local hydrogen-bond dynamics in the condensate and compare the measurements with molecular dynamics simulations. Hydrogen bond lifetimes undergo a marked slowdown compared to dynamics in the dilute phase. This is representative of confined water within the percolated networks inside the condensate due to the interaction present in the condensate disrupting H-bond networks. Overall, our results show that both protein structure and dynamics are inherently dependent on the type of interactions that stabilize the condensates.

Enantioenriched phosphorus(V)-stereogenic compounds, featuring a pentavalent phosphorus atom as the stereogenic center, are crucial in various natural products, drugs, bioactive molecules, and catalysts/ligands. While a handful of stereoselective synthetic approaches have been developed, achieving direct stereocontrol at the phosphorus atom through catalytic generation of phosphorus(V)-heteroatom bonds continues to be a formidable challenge. Here, we disclose an organocatalytic asymmetric condensation strategy that employs a novel activation mode of stable feedstock phosphinic acids by the formation of mixed phosphinic anhydride as the reactive species to facilitate further catalyst-controlled asymmetric P–O bond formations, involving a dynamic kinetic asymmetric transformation (DYKAT) process with alcohol nucleophiles via a cinchonidine-derived bifunctional catalyst. The resulting H-phosphinate intermediates allow further stereospecific derivatizations, affording modular access to a diverse library of chiral phosphonates and phosphonamidates with notable antibacterial activity. Furthermore, this synthetic platform facilitates P–O/N coupling with various natural products and drugs, presenting a valuable tool for medicine and agrochemical discovery.

Transition metal dichalcogenide (TMDC) nanowires have practical applications in 1D electron channels, spintronics, optoelectronics, and catalysis due to their authentic subnanometer width (<1 nm) and intrinsic metallicity. Although narrowing of a TMDC nanoribbon into a nanowire under electron irradiation has been frequently observed in the synthesis of TMDC nanowires, the mechanism underlying this unexpected structural transformation remains a mystery. Here, to reveal the underlying mechanism, we combine first-principles calculations with a global structure search of 1D nanowires and show that a nanoribbon of 1H-phase MoS₂ with a width narrower than 6 rings is energetically unfavorable compared with its nanowire counterpart due to the edge–edge interaction. The bending effect induced by S defects under electron irradiation is the major driving force for the transition of MoS₂ nanoribbon into a nanowire. We predict that the precursor of the Mo₆S₆ nanowire is a well-defined Mo₁₁S₁₁-i nanowire with an unexpected stoichiometry. The intrinsic local compressive strain triggers a phase transition from Mo₁₁S₁₁-i to its slightly modified sister nanowire, Mo₁₁S₁₁-ii, which is characterized by the configuration (Mo₁S₁)₅&Mo₆S₆. Triggered by electron irradiation, the nanoribbon undergoes a step-by-step narrowing process with sequential peeling of a Mo₁S₁ fragment in each step to form a robust Mo₆S₆ nanowire. This unique narrowing mechanism is universal for the nanoribbon-to-nanowire transformation of other TMDCs under electron irradiation. Our study highlights a hitherto unexplored mechanism for creating individual M₆X₆ nanowires and contributes to an in-depth understanding of the narrowing of TMDC nanoribbons under electron irradiation.

Chirality is a ubiquitous feature in biological systems and occurs even in certain inorganic crystals. Interestingly, some inorganic nanocrystals have been shown to possess chirality, despite their achiral bulk forms. However, the mechanism of chirality formation and chiroptical responses in such nanocrystals is still ambiguous due to the presence of chiral organic ligands used to passivate such nanocrystals. Here, we recognize intrinsic chiroptical responses from lead halide perovskite nanowires with different length scales. Cube-connected nanowires with minimum interfacial contacts make their arrangement chiral for chiroptical responses even in the absence of chiral ligands. The chiral nanowires with varying lengths serve as a systematic platform for improving dissymmetric factors significantly with increasing lengths. The dissymmetric factor of the longest nanowires reaches 1.4 × 10^–2, which is the highest among the intrinsic chiral perovskite nanocrystals at present. The nanowires generate circularly polarized luminescence, which has been seldom reported in halide perovskite nanocrystals in the absence of any chiral ligands. Furthermore, we find that chirality exists in the basic unit consisting of two corner-connected cubes in the form of a dimer. The intrinsic chirality of the nanowires is determined by the lattice rotation of connected cubes along the interfacial boundaries, which is different from the commonly observed chirality induced by chiral ligands. Such chiral lead halide perovskite nanocrystals with robust chiroptical properties provide an ideal platform for understanding the origin of intrinsic chirality and the rational design of anisotropic chiral nanostructures.

Desymmetrization of meso diols is an important strategy for the synthesis of chiral oxygen-containing building blocks. Oxidative desymmetrization is an important subclass, but existing methods are often constrained by the need for activated alcohol substrates. We disclose a conceptually distinct strategy toward oxidative diol desymmetrization that is enabled by catalytic enantioselective hydrogen atom abstraction. Following single electron oxidation of a cinchona alkaloid-derived catalyst, enantiodetermining hydrogen atom abstraction generates a desymmetrized ketyl radical intermediate which reacts with either DIAD or O₂ before in situ elimination to form valuable hydroxyketone products. A range of cyclic and acyclic meso diols are competent, defining the absolute configuration of up to four stereocenters in a single operation. As well as providing rapid access to complex hydroxyketones, this work emphasizes the broad synthetic potential of harnessing hydrogen atom abstraction in an enantioselective manner.

Molecular imaging with analyte-responsive probes offers a powerful chemical approach to studying biological processes. Many reagents for bioimaging employ a fluorescence readout, but the relatively broad emission bands of this modality and the need to alter the chemical structure of the fluorophore for different signal colors can potentially limit multiplex imaging. Here, we report a generalizable approach to multiplex analyte imaging by leveraging the comparably narrow spectral signatures of stimulated Raman scattering (SRS) in activity-based sensing (ABS) mode. We illustrate this concept with two copper Raman probes (CRPs), CRP2181 and CRP2153.2, that react selectively with loosely bound Cu(I/II) and Cu(II) ions, respectively, termed the labile copper pool, through copper-directed acyl imidazole (CDAI) chemistry. These reagents label proximal proteins in a copper-dependent manner using a dye scaffold bearing a ¹³C≡N or ¹³C≡¹⁵N isotopic SRS tag with nearly identical physiochemical properties in terms of shape and size. SRS imaging with the CRP reagents enables duplex monitoring of changes in intracellular labile Cu(I) and Cu(II) pools upon exogenous copper supplementation or copper depletion or genetic perturbations to copper transport proteins. Moreover, CRP imaging reveals reciprocal increases in labile Cu(II) pools upon decreases in activity of the antioxidant response nuclear factor-erythroid 2-related factor 2 (NRF2) in cellular models of lung adenocarcinoma. By showcasing the use of narrow-bandwidth ABS probes for multiplex imaging of copper pools in different oxidation states and identifying alterations in labile metal nutrient pools in cancer, this work establishes a foundation for broader SRS applications in analyte-responsive imaging in biological systems.

Halide oxidation plays a fundamental role in halide segregation and the degradation of halide perovskites, yet quantitative measurement of halide oxidation in solid-state perovskite samples remains challenging. Herein, we demonstrate that in situ opto-gravimetric measurements based on a quartz crystal microbalance can quantify the photolysis kinetics of solid-state perovskites. By investigating a series of mixed bromide/iodide perovskites with varying halide ratios, we demonstrate identical compositional thresholds (x ∼ 0.4 in the CsPb(Br_xI_1–x)₃ system) for iodide oxidation, light-induced halide segregation, and photolysis. Our findings reveal the correlation between these light-induced instabilities and unambiguously explain the photolysis mechanism of mixed-halide perovskites. We also show that photolysis renders the perovskite film more n-type without involving lead reduction. This study introduces a powerful methodology for quantitatively analyzing the mass loss kinetics of halide perovskites under both practical operational and accelerated aging conditions, offering deeper insights into the mechanisms of perovskite degradation.

C–H···π interactions, a prevalent intermolecular force, play a pivotal role in chemistry, materials science, and life sciences. Despite extensive studies of their influence on intermolecular binding configurations and energetics, their impact on intermolecular coupling and charge transport remains unexplored. Here, we investigate the charge transport within supramolecular junctions connected by C–H···π and π–π interactions, respectively, and find that C–H···π interactions exhibit conductances that are 3.5 times those of π–π interactions. Angstrom-scale distance-dependent experiments indicate that the conductance of C–H···π supramolecular junctions experiences initial decay under stretching, followed by gradual convergence, in contrast with the periodic fluctuations in π–π stacked supramolecular junctions. Theoretical calculations show that charge transport within C–H···π interactions transitions from destructive to constructive quantum interference under stretching, with a larger range of constructive quantum interference compared with π–π stacking. This study establishes that C–H···π interactions facilitate efficient intermolecular charge transport and elucidates the evolution of quantum interference effects with assembly configuration, offering critical insights for the design of supramolecular materials and devices.

Properties of layered superconductors can vary drastically when thinned down from bulk to monolayer owing to the reduced dimensionality and weakened interlayer coupling. In transition metal dichalcogenides (TMDs), the inherent symmetry breaking effect in atomically thin crystals prompts novel states of matter such as Ising superconductivity with an extraordinary in-plane upper critical field. Here, we demonstrate that two-dimensional (2D) superconductivity resembling those in atomic layers but with more fascinating behaviors can be realized in the bulk crystals of two new TMD-based superconductors Ba_0.75ClTaS₂ and Ba_0.75ClTaSe₂ with superconducting transition temperatures 2.75 and 1.75 K, respectively. They comprise an alternating stack of H-type TMD layers and Ba–Cl layers. In both materials, intrinsic 2D superconductivity develops below a Berezinskii–Kosterlitz–Thouless transition. The upper critical field along the ab plane (Hc2||ab) exceeds the Pauli limit (μ₀H_p); in particular, Ba_0.75ClTaSe₂ exhibits an extremely high μ0Hc2||ab≈ 14 μ₀H_p and a colossal superconducting anisotropy (Hc2||ab/Hc2⊥ab) of ∼150. Moreover, the temperature-field phase diagram of Ba_0.75ClTaSe₂ under an in-plane magnetic field contains a large phase regime of vortex dissipation, which can be ascribed to the Josephson vortex motion, signifying an unprecedentedly strong fluctuation effect in TMD-based superconductors. Our results provide a new path toward the establishment of 2D superconductivity and novel exotic quantum phases in bulk crystals of TMD-based superconductors.

Adsorption capacity prediction, which needs to be based on the precise structure–capacity relationship, is important for better adsorbent design. However, the precise adsorption contribution coefficients of pores of different sizes for volatile organic compound (VOC) adsorption remain unclear. Herein, a control variable method is employed as a generative model to realize the numerization of the precise structure–capacity relationship. For the first time, a concise equation is proposed that can predict the adsorption capacities/isotherms of unknown adsorbents through their pore structure parameters. Interestingly, practical VOC adsorption amounts aligned with predicted values obtained by simultaneously considering pore volume (which undergoes volume-filling adsorption) and surface area (which undergoes surface-covering adsorption) as input variables. Derivation of the equation is based on classical adsorption theories and mathematical expression of the precise structure–capacity relationship obtained from actual experimental results. Each parameter in the equation has a specific physical meaning. This unprecedented VOC adsorption capacity/isotherm prediction method provides in-depth insight for accurate quantification of VOC adsorption, with great potential for gas adsorption prediction and guidance in the development of adsorption materials and technologies.

Metal-oxide aqueous interfaces are important in areas as varied as photocatalysis and mineral reforming. Crucial to the chemistry at these interfaces is the structure of the electrical double layer formed when anions or cations compensate for the charge arising from adsorbed H⁺ or OH^–. This has proven extremely challenging to determine at the atomic level. In this work, we use a surface science approach, involving atomic level characterization, to determine the structure of pH-dependent model electrified interfaces of TiO₂(110) with HCl and NaOH using surface X-ray diffraction (SXRD). A comparison with ab initio molecular dynamics calculations reveals the formation of surprisingly compact double layers. These involve inner-sphere bound Cl and Na ions, with respectively H⁺ and O^–/OH^– in the contact layer. Their exceptionally high electric fields will play a key role in determining the chemical reactivity.

The key to controlling the fabrication process of transition metal sulfide nanocrystals is to understand the reaction mechanism, especially the coordination of ligands and solvents during their synthesis. We utilize in situ high-energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) as well as in situ valence-to-core X-ray emission spectroscopy (vtc-XES) combined with density functional theory (DFT) calculations to identify the formation of a tetrahedral [Zn(OA)₄]²⁺ and an octahedral [Zn(OA)₆]²⁺ complex, and the ligand exchange to a tetrahedral [Zn(SOA)₄]²⁺ complex (OA = oleylamine, OAS = oleylthioamide), during the synthesis of ZnS nanorods in oleylamine. We observe in situ the transition of the electronic structure of [Zn(SOA)₄]²⁺ with a HOMO/LUMO gap of 5.0 eV toward an electronic band gap of 4.3 and 3.8 eV for 1.9 nm large ZnS wurtzite nanospheres and 2 × 7 nm sphalerite nanorods, respectively. Thus, we demonstrate how in situ multimodal X-ray spectroscopy and scattering studies can not only resolve structure, size, and shape during the growth and synthesis of NPs in organic solvents and at high temperature but also give direct information about their electronic structure, which is not readily accessible through other techniques.

The synthetic toolbox for stimuli-responsive polymers has broadened to include many tunable variables, making these materials applicable in diverse technologies. However, unraveling the key composition–structure–function relationships to facilitate ground-up design remains a challenge due to the inherent dispersity in sequence and conformations for synthetic polymers. We here present a systematic study of these relationships using a model system of copolymers with a thermoresponsive (N-isopropylacrylamide) backbone in addition to metal-chelating (acrylic acid) and hydrophobic structural comonomers and evaluate their efficiency at isolating technologically critical lanthanide ions. The efficiency of lanthanide ion extraction by precipitation was quantitated with a metallochromic dye to reveal trends relating copolymer hydrophobicity to improved separations. Further, we examined the role of different hydrophobic comonomers in dictating the solution-phase conformation of the polymer in the presence and absence of lanthanide ions, and we correlated key features of the hydrophobic comonomer to extraction efficiency. Finally, we identified how the local proximity of thermoresponsive, chelating, and hydrophobic subunits facilitates metal extraction by manipulating the copolymer sequence with multiblock polymerization. Through mechanistic analysis, we propose a binding-then-assembly process through which metal ions are coprecipitated with macromolecular chelators.

Defects in two-dimensional materials profoundly impact the physicochemical properties of the systems, whose characterization is highly desirable at the atomic scale. Here, using spectroscopic imaging scanning tunneling microscopy, we elucidate the vibrational and magnetic states of Mo_Se antisite and V_Mo vacancy with different charge states embedded in ultrathin MoSe₂ bilayers supported on graphene substrate. Stringent vibronic states with multimode coupling are resolved on the defects. The spectral intensities are tunable with the electron tunneling rates and well-reproduced by theoretical modeling. Moreover, first-principles calculations suggest that the defects host a local magnetic moment of 2 μ_B in their neutral state, which is directly confirmed by our spin-flip inelastic electron tunneling spectroscopy. Our study deepens the understanding of defect properties and paves the way of defect-engineering material functionalities and spin-catalytic applications.

Engineering microstructures of Pt and understanding the related catalytic mechanism are critical to optimizing the performance for hydrogen evolution reaction (HER). Herein, Pt dispersion and coordination are precisely regulated on hierarchical nitrogen-doped carbon nanocages (hNCNCs) by a thermal-driven Pt migration, from edge-hosted Pt–N₂Cl₂ single sites in the initial Pt₁/hNCNC-70 °C catalyst to Pt clusters/nanoparticles and back to in-plane Pt–N_xC_4–x single sites. Thereinto, Pt–N₂Cl₂ presents the optimal HER activity (6 mV@10 mA cm^–2) while Pt–N_xC_4–x shows poor HER activity (321 mV@10 mA cm^–2) due to their different Pt coordination. Operando characterizations demonstrate that the low-coordinated Pt–N₂ intermediates derived from Pt–N₂Cl₂ under the working condition are the real active sites for HER, which enable the multi-H adsorption mechanism with an ideal H* adsorption energy of nearly 0 eV, thereby the high activity, as revealed by theoretical calculations. In contrast, the high-coordinated Pt–N_xC_4–x sites only allow the single-H adsorption with a positive adsorption energy and thereby the low HER activity. Accordingly, with an ultralow Pt loading of only 25 μg_Pt cm^–2, the proton exchange membrane water electrolyzer assembled using Pt₁/hNCNC-70 °C as the cathodic catalyst achieves an industrial-level current density of 1.0 A cm^–2 at a low cell voltage of 1.66 V and high durability, showing great potential applications.

Proton exchange membrane water electrolyzers powered by sustainable energy represent a cutting-edge technology for renewable hydrogen generation, while slow anodic oxygen evolution reaction (OER) kinetics still remains a formidable obstacle that necessitates basic comprehension for facilitating electrocatalysts’ design. Here, we report a low-iridium complex oxide La_1.2Sr_2.7IrO_7.33 with a unique hexagonal structure consisting of isolated Ir(V)O₆ octahedra and true peroxide O₂^2– groups as a highly active and stable OER electrocatalyst under acidic conditions. Remarkably, La_1.2Sr_2.7IrO_7.33, containing 59 wt % less iridium relative to the benchmark IrO₂, shows about an order of magnitude higher mass activity, 6-folds higher intrinsic activity than the latter, and also surpasses the state-of-the-art Ir-based oxides ever reported. Combined electrochemical, spectroscopic, and density functional theory investigations reveal that La_1.2Sr_2.7IrO_7.33 follows the peroxide-ion participation mechanism under the OER condition, where the inherent peroxide ions with accessible nonbonded oxygen states are responsible for the high OER activity. This discovery offers an innovative strategy for designing advanced catalysts for various catalytic applications.

Complex physical barriers and the nanomaterial’s clearance mechanism in the liver greatly hinder the feasibility of using a conventional liver-targeting nanoplatform to deliver antifibrotic drugs to pathological sites for the treatment of liver fibrosis. Here, a novel drug delivery strategy was designed to overcome drug penetration barriers in a fibrotic liver and cooperated with oral nattokinase (NKase)-mediated antifibrosis therapy as a proof of concept, which relies on the coadministration of a nanosized iron-locked drug generator (named Pro-HAase) and orally absorbed iron chelator deferasirox (DFX). Such a strategy starts from the rapid accumulation of intravenously injected Pro-HAase in the microcapillaries of the fibrotic liver followed by disrupting the polyphenol-iron coordination inside Pro-HAase by DFX, liberating antifibrotic components, including procyanidine (PA) and hyaluronidase (HAase). Attractively, absorption of DFX requires the sequential processes of traversing the intestinal mucosa and targeting the liver, which enable DFX to preferentially disassemble Pro-HAase accumulated in the liver sinusoid rather than in systemic circulation or other organs, thus avoiding the off-target activation of Pro-HAase and depletion of the normal iron pool. The in situ disassembly process decreases the sequestration of Pro-HAase by cells of the mononuclear phagocyte system and promotes gradient-driven permeation of therapeutic components to surrounding liver tissues within 2 h, accompanied by biliary excretion of the inactive iron-DFX complex. As a result, the cooperation of Pro-HAase and DFX not only allows NKase-mediated therapy to completely reverse liver fibrosis but also suppresses the chronic hepatotoxicity of residual liver iron after multiple doses of Pro-HAase. The high spatiotemporal precision, unique barrier-penetration mechanism, and self-detoxification ability of this strategy will inspire the rational design of analogous iron-locked nanosystems to improve the therapeutic outcomes of liver fibrosis or other liver diseases.

Crown ethers are central to supramolecular chemistry, recognizing and binding specific ions in solution. The most well-known, 18-Crown-6 (18C6), preferentially captures K⁺ in an aqueous solution, while gas phase binding of 18C6 with alkali metal ions decreases linearly with an increasing ionic radius. Why the high affinity for Li⁺ and Na⁺ in the gas phase is dramatically reduced with hydration remains an open question in understanding the K⁺ selectivity in the aqueous phase. A combined spectroscopic and computational study of M⁺18C6(H₂O)_n=0–3 (M = Li, Na, and K) in the CH stretch region has revealed how stepwise hydration unbuckles the crown ether belt from Li⁺ and Na⁺, substantially changing the backbone structure of 18C6. In contrast, the structure of the K⁺18C6 complex is unbuckled and is unaffected by hydration. Combined with new measurements of the OH stretch, a direct connection is provided between the stepwise hydration of M⁺18C6 and the selectivity for K⁺ in an aqueous solution. It demonstrates and validates at the molecular level the application of gas-phase measurements to condensed-phase studies.