Browse Articles

Synthesis of Chiral Triarylmethanes via Catalytic Asymmetric Skeletal Editing

Abstract Catalytic asymmetric skeletal editing (CASE) has emerged as a powerful strategy for accessing chiral organic molecules through enantioselective modification of parent molecular skeletons. Herein, we report an enantioselective Rh-catalyzed single-carbon insertion into indole rings with diazoesters via either desymmetrization or kinetic resolution, thereby enabling arene-to-arene transmutation and, for the first time, the construction of exocyclic carbon-centered stereocenters. Starting from indole-containing triarylmethanes, a broad range of optically active triarylmethanes bearing diverse arene/heteroarene combinations with distinct aromatic electronic properties were obtained in moderate to good yields and high enantioselectivities (up to 96% ee). The method was further extended to desymmetrizing skeletal editing of alkyl- and alkenyl-substituted bis(indolyl)methanes, indole-containing simple natural products and pharmaceutical motifs. Its potential for structural transmutation was further demonstrated by a 3-fold programmable skeletal editing sequence of an indene-substituted bis(indolyl)methane.

3D Electron Microscopy Reveals Evidence for Strong Electric Fields at Nanoconfined Air–Water Interfaces

Abstract Strong electric fields at air–water interfaces are widely invoked to explain accelerated interfacial chemistry, yet direct, probe-free evidence under evaporation-free conditions has remained challenging. Here, we confine aqueous solutions and air within ∼50 nm-diameter multiwalled carbon nanotubes to stabilize nanoscale air–water interfaces for three-dimensional transmission electron microscopy. Reconstructed multiphase structures reveal ∼10 nm gas domains separated from the nanotube walls by ultrathin water films spanning molecular to nanometer thicknesses. Curvature analysis yields Laplace and disjoining pressure distributions indicating a repulsive pressure of ∼10 MPa that prevents film collapse. This repulsion is consistent with an interfacial electric field on the order of several volts per nanometer, primarily associated with oriented water dipoles and potentially enhanced by the electric double layer. Consistent with this inferred field strength, the reduction of chloroauric acid (HAuCl4) to gold nanoparticles occurs exclusively within ∼2 nm of the interface. These results provide evidence for intense, spatially confined electric fields at air–water interfaces through the combined observations of strong non-Derjaguin–Landau–Verwey–Overbeek repulsive pressures and localized interfacial Au reduction and establish their fundamental role in nanoscale interfacial chemistry across chemical, environmental, and energy-relevant systems.

A Glimpse into the Initial Microsecond of Biomolecular Condensation

Abstract Biomolecular condensation is a key process for cells to maintain their normal physiological activities. However, the process of phase transition remains mysterious, especially for the initial moments of condensation. Herein, we investigated the first microsecond of peptide condensation through temperature jump infrared spectroscopy and molecular dynamics simulations. These techniques overcome the limited spatiotemporal resolution of traditional approaches, allowing us to capture the molecular events and kinetic information on the initial moment for phase transition. The results reveal that structural transitions and early assembly of intrinsically disordered proteins occur on ultrafast time scales. Unexpectedly, backbone hydrogen bonding emerges as the overlooked key mediator to stabilize the local structure for the ultrafast condensation of hydrophobic polypeptides compared to hydrophobicity. By locking local structures, hydrogen bonds help to form more stable interaction interfaces. These findings indicate that hydrogen bonding could enable hydrophobic disordered proteins to adopt preorganized conformations in response to environmental stimuli and serve as a key factor in mediating the assembly kinetics in complex cellular environments.

Antiaromatic Cyclooctatetraene-Embedded, BODIPY-Fused Nanographene with an NIR-II Chiroptical Response

Abstract Chiral nanographenes exhibiting near-infrared (NIR) chiroptical responses are of growing interest due to their potential applications in bioimaging, sensing, and photodetectors. Nevertheless, realizing the chiroptical response in the NIR-II region (1000–1700 nm) remains a fundamental challenge. Herein, a BODIPY-fused anthracene (BNG1) and an unprecedented BODIPY-fused nanographene (BNG2) incorporating a cyclooctatetraene (COT) unit are synthesized. Single-crystal X-ray crystallography confirms their structures, revealing that BNG2 adopts an enantiomeric double-helical architecture. The embedded COT unit possesses a pronounced antiaromatic character, as supported by multiple theoretical analyses. Both compounds display strong absorption spanning the UV–visible–NIR regions, especially the π-extended BNG2, which shows broad absorption with a long tail reaching 1800 nm in toluene solution, attributed to the antiaromaticity and low C2-symmetry of COT. BNG1 and BNG2 have narrow optical energy gaps of 1.32 and 0.90 eV, H-aggregation behaviors, and excellent photothermal stability. Most importantly, enantiomers of BNG2 are successfully resolved by chiral high-performance liquid chromatography and exhibit mirror-image circular dichroism spectra with opposite Cotton effects extending from the UV region to the NIR-II region. This implies its potential applications in the detectors of wide-range circularly polarized light and chirality-based phototherapy. Our investigation provides important insights into developing purely organic materials with robust NIR chiroptical responses.

Machine Learning-Assisted Development of High-Performance Ethanol Synthesis Catalysts via CO2 Hydrogenation

Abstract The discovery and development of high-performance catalysts, which is crucial across all catalysis areas, requires advanced technologies and innovative approaches. Recently, machine learning (ML) has shown promise in accelerating this process, but its capability and examples of discovery of truly novel catalysts have remained limited. In this study, we describe an ML approach that goes beyond the traditional element pool, incorporating elements that have not been previously studied, to develop highly efficient catalysts for ethanol synthesis via CO2 hydrogenation. Starting with an initial data set of 58 catalysts (274 data points obtained at reaction temperatures ranging from 240–400 °C), we conducted 24 iterations of a closed-loop discovery system (ML predictions + experimental validation), testing a total of 555 catalysts (2477 data points), and building a large experimental data set. More than 50 catalysts with superior activity were discovered through this data-driven approach. The multielemental Pd(0.8)–Au(0.3)/K(2.5)–Sr(1)–Fe(20)–Zn(4)–Cd(2)–Yb(1)–Re(1)/CeO2(25%)-ZrO2 catalyst, where the numbers in parentheses represent weight percent (wt %), was identified as the most effective catalyst for ethanol synthesis (ethanol space–time yield: 8.2 mmol gcat–1 h–1 with a CO2 conversion of 57.6% and an ethanol selectivity of 23.2% under reaction conditions of 360 °C, 4 MPa, 12 L gcat–1 h–1, H2/CO2 = 3/1). Comprehensive characterizations, including in situ/operando techniques such as X-ray absorption spectroscopy (XAS), ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), enable us to highlight the critical roles of each constituting element in improving ethanol synthesis efficiency.

Miniaturized HOXB13 Mimetics Are Sequence-Specific, Methyl-Sensitive DNA Binders

Abstract Homeobox protein Hox-B13 (HOXB13) is an oncogenic transcription factor that is associated with prostate cancer risk. Unlike most transcription factors (TFs), HOXB13 is a methyl-plus TF and has been shown to be preferentially recruited to DNA prostate cancer risk loci. Here, we miniaturized HOXB13 to create metal-stapled mimetics that can target its cognate primary DNA-binding site in a sequence-specific, methyl-sensitive manner. Targeted profiling of 5-methylcytosine (5mC) recognition using V269X mimetic mutants revealed that leucine can further enhance both methyl sensitivity and methyl specificity through methyl–methyl contact with 5mC and decreased methyl–pi interactions with cytosine. Collectively, our study revealed novel insights into the molecular interactions of HOXB13 with methylated DNA and new tools that will provide a structural basis for future development of a new class of sequence-specific methylated DNA binders.

Photocatalytic Oxidative Coupling of Methane over SrTiO3 Overlayers on Au Nanoparticles

Abstract Photocatalytic oxidative coupling of methane (OCM) is a prevailing method to access multicarbon (C2+) hydrocarbons. However, the kinetically slow C–C coupling of the methyl radical hinders the overall methane coupling reaction and leads to overoxidation side reactions. Here we report photocatalytic OCM over SrTiO3 supported, SrTiO3 overlayer coated Au nanoparticles (Au@SrTiO3). The SrTiO3 support and overlayers capture photogenerated holes to activate the methane C–H bond. C–C coupling between the methyl radical intermediate is rate limiting and occurs with an improved selectivity of 93% over the SrTiO3 overlayers on Au nanoparticles (NPs). The Au@SrTiO3 catalyst is stable for more than 300 h, affording C2H6 with a formation rate of 155 μmol h–1, 7 times that of Au/SrTiO3 without SrTiO3 overlayers. The activity is improved to 1050 μmol h–1 with a C2+ selectivity of 94% by increasing Au@SrTiO3 loading to harvest more light. These figures of merits are comparable with the benchmarking photocatalysts for OCM by elucidating the chemistry of C–C coupling sites.

<i>In Situ</i> Construct of Zn–In Alloy Layer by In(BF4)3 Additive to Stabilize Zn Anode and Realize Ultra-High Reversible Zinc–Air Batteries

Abstract Aqueous zinc–air battery (ZAB) is considered as a promising long-term energy storage technology due to its low cost, high safety, and high theoretical energy density. However, the zinc (Zn) anode suffers from issues such as dendrite growth, hydrogen evolution reaction (HER), corrosion, passivation, and volume deformation during cycling. To enhance the interfacial stability and deposition/dissolution behavior of the Zn anode, this work introduces indium tetrafluoroborate (In(BF4)3) into the electrolyte as a functional additive. The results demonstrate that the incorporation of indium (In) effectively regulates Zn nucleation behavior, promotes uniform Zn deposition, and significantly suppresses dendrite formation. Moreover, the dynamic alloy interface formed with In participates in reversible redox reactions that enable local defect self-healing, thus improving interfacial integrity and the compactness of the deposited structure. After modification, the ZAB achieves an ultralong cycle life of over 400 h under a current density of 5 mA cm–2 and 20 min per cycle, and ultrahigh reversibility for 320 h at current density of 2 mA cm–2 and 4 h per cycle under high depth of discharge/charge. The ZABs with In(BF4)3 additive exhibit reduced voltage polarization and excellent rate capability at various current densities, exhibiting enhanced cycling stability and electrochemical performance significantly. This work shows clearly the strategy of in situ constructing a Zn–In alloy layer by electrolyte engineering, which can guide the design and preparation of a stable Zn anode for not only ZABs but also the other Zn-based batteries.

Controlled Synthesis of Chiral β-Chloramines and Aziridines via an Organo- and Biocatalytic Cascade

Abstract Chiral organochlorides bearing C–Cl stereocenters are highly desirable motifs in synthetic and medicinal chemistry, yet their direct asymmetric synthesis from simple starting materials via biocatalysis alone remains challenging. Here, we report an integrated organo- and biocatalytic cascade that converts readily available aldehydes into enantiomerically enriched β-chloramines. Under optimized near-neutral conditions, the method delivers a broad array of β-chloramines in high yield (up to 88%) with exceptional enantioselectivity (up to &amp;gt;99:1 enantiomeric ratio). Notably, by simply raising the pH to 9.5, the same cascade system diverges to directly generate chiral aziridines, enabling pH-controlled access to two valuable product classes from a unified platform. The utility of this strategy is further demonstrated by preparative-scale syntheses from inexpensive commercial substrates, followed by divergent linchpin transformations to diverse chiral building blocks, including aziridines, azido amines, and acetoxy amines. Mechanistic studies provide insight into the origins of stereoselectivity and the key factors governing stereochemical outcomes.

Beyond Dealumination: Does Fluorine Reshape Zeolitic Acidity?

Abstract Fluoride-containing media have been widely adopted in the post-treatment of ZSM-5 zeolites for heterogeneous catalysis. Their effects have predominantly been discussed in terms of the well-established dealumination process. However, comparatively little attention has been paid to the influence of residual fluorine on the local chemical environment, which governs zeolitic acidity and catalytic performance. In this work, mild fluorination of ZSM-5 was achieved by controlling the ammonium fluoride (NH4F) content during hydrothermal treatment. Our findings reveal that fluorine induces significant perturbations in the acidic properties of ZSM-5, distinct from the conventional dealumination effect. To elucidate these effects at the atomic level, we employed 27Al, 19F, 27Si, and 1H solid-state magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, which provided detailed chemical and structural insights. The correlated incorporation of fluorine within the zeolite framework leads to strong local polarization, thereby enabling the protons to exhibit Brønsted acid site (BAS)-like behavior. Comparative analysis with nonaluminum-containing silicalite-1 further confirmed the fluorine-induced acidity, as supported by two-dimensional (2D) 1H double-quantum single-quantum (DQ–SQ) MAS NMR results. Catalytic testing in the methanol-to-hydrocarbon (MTH) reaction demonstrated that such fluorinated ZSM-5 exhibits an extended catalytic lifetime along with enhanced aromatic selectivity, underscoring the pivotal electronic influence of fluorine beyond its classic role in dealumination.

Bis-Tetrazine Fluorogenic (Silicon)-Rhodamine Dyes for Live-Cell Labeling

Abstract Fluorogenic click dyes are valuable tools for biorthogonal labeling, enabling real-time visualization of biomolecules and cellular processes in their native environments. However, achieving efficient quenching and high fluorescence turn-on within a single dye scaffold remains a significant challenge. Herein, we report a class of fluorogenic click dyes based on a structural modification of (silicon)-rhodamines at the amino groups of the xanthene scaffold, resulting in a particularly short linker and a highly optimized quenched state. This modification enables the synthesis of both mono- and bis-functional derivatives. The monofunctional dyes are fully compatible with established click-labeling strategies and display exceptional fluorogenic responses, with fluorescence enhancements of up to 2 orders of magnitude. Notably, the bis-functional derivatives are fluorogenic dyes that exhibit fluorescence turn-on ratios approaching 3 orders of magnitude upon biorthogonal reaction, making them particularly suitable for live-cell applications. We show that the short bis-linker has high potential for anisotropy measurements that can report on protein size and dynamics. We further demonstrate the unique utility of these bis-functional dyes for peptide cyclization, enhancing cellular uptake while enabling real-time visualization. Together, this work introduces a versatile dye class that substantially expands the scope of click chemistry and will advance applications in live-cell imaging as well as studies of protein structure and dynamics.

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Issue Editorial Masthead

Photoinduced Enhancement of Chemical Shift Sensitivity to Local Vibrations

Abstract The advent of novel free-electron laser sources enabling time-resolved X-ray photoelectron spectroscopy (tr-XPS) provides a unique opportunity to monitor local chemical environments in real time by measuring sub-eV shifts in core-electron binding energies. These shifts reflect the interplay between electronic excitation and nuclear motion, an interplay that remains largely unexplored. In our combined theoretical and experimental study of fluoropyridine (C5H4FN), we investigate this link by monitoring the evolving chemical environment at the N and F atomic sites as the photoexcited S1 state relaxes to the ground state via a conical intersection. We find that the F site responds primarily to vibrational relaxation, showing minimal sensitivity to the electronic excited state. In contrast, excitation to S1 induces a measurable energy shift at the N site and significantly enhances its sensitivity to local vibrations within the ring. This behavior arises from a photoinduced redistribution of charge, which also increases the Coulomb interaction between the 1s electron at the N atom and the atomic partial charge at an adjacent C atom. This insight opens new avenues for exploring ultrafast dynamics and conical intersection pathways in more complex systems, from photostable DNA bases to light-harvesting materials.

Phase 3 Trial of Weekly Oral Islatravir–Lenacapavir for HIV-1 Treatment

Pregnancies in Patients with Autoimmune Disease Receiving CAR T-Cell Therapy

The Inequality–Pandemic Cycle — Rethinking Preparedness

iEvac-Z, an Inactivated Ebola Vaccine — Phase 1 Study in Japan

How antiretroviral data cleaning reshaped Mozambique’s progress to reaching HIV epidemic control

Quality data is fundamental for any public health program, especially for long-term care programs that rely on longitudinal data for decision making. In Mozambique, there had been a growing discrepancy between the number of people living with HIV (PLHIV) on antiretroviral treatment (ART) reported in the national system when compared to pharmacy and electronic medical records. A national ART data cleaning exercise was conducted in the first semester of 2024 to improve the accuracy and reliability of the nationally reported data. All health facilities with ART services (n = 1,757) compared their nationally reported data between the clinical data available at the health facility and the pharmacy medication pick-up data. The records that were successfully validated were marked as active, while the others were non-active. Upon completion of the review, the nationally reported data were revised. There was a 9.9% decrease (2,166,941–1,951,724) in the number of PLHIV considered currently on ART between December 2023 and June 2024. Among age groups, there was a 28.7% decrease among those less than 10 years of age, 26.4% among those between 10 and 19 years, and 8.0% for those 20 years or more. Cabo Delgado was the province with the largest percentage difference (21.1%, −28,799 PLHIV currently on treatment), while Zambezia had the largest absolute decline, of 41,445 (−8.9%). The notable decreases in PLHIV on ART resulted in an increase in Mozambique’s estimates for new infections, AIDS-related deaths, and vertical transmission. These updates allowed for a more realistic understanding of the HIV epidemic in Mozambique, including highlighting provinces with large data quality issues evidenced by substantial changes in PLHIV on ART numbers. This activity highlighted challenges that exist in paper-based reporting systems and provides evidence for a renewed focus on improving data quality for decision making.

A designathon to collaboratively develop sustainable HIV prevention services for youth with community-based organizations in Nigeria

Introduction The engagement of youth in the design of services that promote and increase the uptake of essential services to reduce HIV and other sexually transmitted infections is vital to sustaining these preventive services. The study objective is to identify strategies for sustaining HIV prevention services among Nigerian youth, in partnership with community-based organizations, through a crowdsourced open call and designathon in Nigeria. Materials and methods From February to March 2024, Nigerian youth (ages 14–24) submitted ideas to an open crowdsourcing call on how community-based organizations in Nigeria might sustain HIV self-testing and youth-friendly preventive services for at-risk youth. The submissions were scored in each domain: relevance, novelty, scalability, replicability, potential for sustainability, and promotion of equity and fairness, with an integer score of 1 (low) to 3 (high)(S1). Ten teams were selected to participate in the 72-hour designathon. Both quantitative and qualitative analysis was conducted. The study used thematic analysis and the PEN 3-Cultural Model to categorize qualitative data into six themes. Descriptive statistics were used to calculate participants’ demographic characteristics. Results One hundred and seventy-eight participants submitted entries; 161 were online entries, and 17 were received via WhatsApp. The majority of participants were female (57.1%) and aged 19–23 years (55.0%), with a mean age of 21.7 (±4.1). Most participants were from the southwest of Nigeria (53.8%), had secondary education (68.9%), and were students (67.9%). About one-third of teams (31.1%) indicated collaborating with non-governmental organizations as a promising way to sustain preventive services. Six themes emerged: Adapted Intervention Design and Delivery, Youth Engagement and Education, Organization Setting, Socio-cultural and Community Context, Community Leadership Through Training and Financial Resources, and Sustainment Through Community Collaboration. Conclusion The crowdsourcing contest open call and designathon engaged youth from diverse backgrounds, and it is a practical way to generate solutions from key stakeholders affected by the community’s prevailing health issues. Developing service delivery strategies that engage, educate, and collaborate with youth on HIV prevention could be sustainable. However, this will not be conclusive without implementing them over time to test their feasibility and sustainability.