Harnessing Radical-Based Dynamic Covalent Chemistry and Supramolecular Synthon for Directional Self-Assembly.

The discovery of new weak supramolecular interactions and supramolecular synthons is essential for directing self-assembly processes with enhanced precision, diversity, and functionality in complex molecular architectures. Here, we report the controlled self-assembly of diverse supramolecular architectures by a new directional bonding approach through the integration of radical-based dynamic covalent chemistry and supramolecular synthons. A novel macrocyclic synthon, , with a linear direction is constructed via radical-based dynamic covalent bonds from the phenothiazine building block substituted with two dicyanomethyl radicals.

Real-Space Quantitative Molecular Analysis at Single-Molecule Resolution.

Advances in molecular analysis and characterization techniques should revolutionize the methods for scientific exploration across physics, chemistry, and biology, fundamentally overturning our understanding of interactions and processes that govern molecular behavior at the microscopic level. Currently, the absence of a molecular analysis method that can both quantify molecules and achieve single-molecule spatial resolution hinders our study of complex molecular systems in sorption and catalysis. Here, we propose a quantitative analysis strategy for small molecules confined in ZSM-5, a zeolite material extensively used in catalysis and gas separation, based on low-dose transmission electron microscopy.

A sequence-activated near-infrared fluorescence probe for precisely tracking senescence.

Real-time monitoring of senescent cells is of great significance for understanding and intervening in aging. Since overexpression of endogenous β-galactosidase (β-gal) is not unique to senescent cells, probes relying solely on β-gal activity could yield inaccurate senescent cell detection. Herein, we designed a dual-mode sequential response AND logic NIR probe MFB-βgal, which contains a β-gal-cleavable unit and a morpholine unit, serving as an enzymatic activity trigger and a lysosomal targeting moiety, respectively.

Identification of a Novel Core Structure of Apo-Ido1 Inhibitors Through Virtual Screening and Preliminary Hit Optimization.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme considered as a potential therapeutic target for neurodegenerative diseases and cancer. However, the further development of traditional IDO1 inhibitors has been hindered by their limited clinical efficacy. Recently, type IV apo-IDO1 inhibitors offer a new strategy for developing IDO1 inhibitors due to their highly selective and durable inhibition.

Albumin Binding Enhances the Lysosomal β-Galactosidase Sensitivity of Fluorogenic Probes Characteristic of Intramolecular Charge Transfer.

Glycosidases generally function in specific organelles to hydrolyze glycoconjugates. Thus, the in situ visualization of glycosidase activities in an organelle-targeted manner can help to better delineate their biological functions. Lysosomal β-galactosidase (β-Gal) is reported to be a biomarker for ovarian cancer and cellular senescence.

Metal-Organic Framework (MOF)-Based Catalysts for Sustainable Energy Technologies: A Review.

The demand for sustainable energy technologies is high due to the depletion and risks linked to fossil fuel usage. Diverse energy technologies, such as regenerative fuel cells, zinc-air batteries, and comprehensive water-splitting devices, possess significant potential for the advancement of green energy. MOFs hold a prominent position among the various kinds of materials utilized in renewable energy technologies.

Ambient-Pressure C-C Coupling of CO Hydrogenation by NiFe/TiO Bimetallic Catalyst.

Catalytic upgrading of CO to value-added C products offers promising solutions to trim carbon emissions with additional economic benefits. Herein, we report a NiFe bimetallic catalyst showing efficient ambient-pressure C-C coupling performance subject to H pretreatment temperature. An optimal performance was achieved after reducing NiFe/TiO at 350 °C (NiFe-350/TiO), yielding 27.

Structure-Based Discovery of Active Pan-KRas Inhibitors Targeting G12D Mutants by Enhanced Sampling Simulations.

Ras is a node protein in the classic tumor signaling pathway known as RAS-RAF-MEK. Mutations in Ras are reported to occur in approximately 19% of human cancers. Among them, the G12D mutation is one of the most prevalent mutations found in Ras.

Thiazolothiazole as a Multimonomer Adapting Organic Catalyst for Atom Transfer Radical Polymerization (ATRP) with Oxygen Tolerance.

Light-controlled organic atom transfer radical polymerization (O-ATRP) has emerged as a mature and advanced method for synthesizing well-defined macromolecules. However, developing a high-performance, low-loading, and oxygen-tolerant O-ATRP catalyst system remains an urgent challenge. Herein, we developed a new O-ATRP catalyst based on 2,5-bis(4-pyridinium) thiazolo[5,4-]thiazole.

An Engineered Supramolecular Fluorescent Chemosensor for Multiscale Visualization of Glutamate Dynamics in Living Systems.

Glutamate (Glu) plays a critical role in the brain, and the ability to directly measure glutamate activity is essential for understanding its physiological functions and pathological processes. Herein, we engineered a family of Glu sensors () based on host-guest interactions through the indicator displacement method (IDA) strategy. The optimized supramolecular chemosensor exhibited specificity, sensitivity, signal-to-noise ratio, rapid kinetics (∼145 ms), and photostability, enabling it to be suitable for monitoring Glu dynamics in neuronal organelles, brain tissues, and zebrafish.

Beyond Density: Unveiling the Trade-Off in Catalytic Site Optimization Using Defect-Engineered UiO-66.

Enhancing intrinsic activity and increasing catalytic site density are two widely employed strategies to improve catalytic performance. Although typically considered independently, their interplay remains poorly understood. Here, two UiO-66 metal-organic frameworks (MOFs) with distinct catalytic site densities-linker-defective UiO-66L and cluster-defective UiO-66C-are synthesized and systematically compared.

Significantly enhancing human antibody affinity via deep learning and computational biology-guided single-point mutations.

Enhancing antibody affinity is a critical goal in antibody design, as it improves therapeutic efficacy, specificity, and safety while reducing dosage requirements. Traditional methods, such as single-point mutations or combinatorial mutagenesis, are limited by the impracticality of exhaustively exploring the vast mutational space. To address this challenge, we developed a novel computational pipeline that integrates evolutionary constraints, antibody-antigen-specific statistical potentials, molecular dynamics simulations, metadynamics, and a suite of deep learning models to identify affinity-enhancing mutations.

Rational Design of Antimony-Based Zintl Clusters: Unveiling Unconventional Bonding and Architectures.

ConspectusThe past decade has witnessed rapid growth in the synthesis of main-group element clusters, driven by advances in the design of Zintl phase precursors and their integration with organometallic reagents. These strategies have unlocked unprecedented structural motifs and bonding patterns, greatly enriching the landscape of main-group cluster chemistry. Among them, antimony-based clusters stand out for their diverse architectures and unique electronic properties, serving as ideal models to explore metalloid aromaticity, multicenter bonding, and unconventional Sb-Sb or Sb-metal interactions.

Divergent Synthesis of -Difluoro-2-oxabicyclo[2.1.1]hexanes Enabled by 1,3-Oxygen Rearrangement.

We present a visible light photocatalytic strategy for efficient synthesis of -difluoro-2-oxabicyclo[2.1.1]hexanes through cross [2 + 2] cyclization of γ,γ- and α,α-difluoroallyl vinyl ethers, which represent a class of novel hybrid bioisosteres.

A Deep Learning-Augmented Density Functional Framework for Reaction Modeling with Chemical Accuracy.

Accurate prediction of reaction energetics remains a fundamental challenge in computational chemistry, as conventional density functional theory (DFT) often fails to reconcile high accuracy with computational efficiency. Here, we introduce Deep post-Hartree-Fock (DeePHF), a machine learning framework that integrates neural networks with quantum mechanical descriptors to achieve CCSD-(T)-level precision while retaining the efficiency of DFT to solve the reaction problems. By establishing a direct mapping between the eigenvalues of local density matrices and high-level correlation energies, DeePHF circumvents the traditional accuracy-scalability tradeoff.

Dynamic construction of a durable epitaxial catalytic layer for industrial alkaline water splitting.

Optimizing the catalyst-electrolyte interface structure is crucial for enhancing the performance of electrochemical alkaline hydrogen evolution reaction. Traditional approaches typically focus on regulating the thermodynamic barriers of adsorption and desorption for reactants, intermediates, and ions at active sites on the solid electrode surface. However, the structure of the electrical double layer influences the concentration of intermediates, adsorption energy, and surface reaction kinetics.

Control Over S(VI) Stereogenicity for the Asymmetric Synthesis of Sulfonimidoyl Derivatives by Isothiourea-Catalyzed Covalent Activation of Sulfur(VI) Atoms.

In contrast to the notable advancements focusing on the preparation of optically enriched S(IV) frameworks in recent years, achieving catalyst stereocontrol over S(VI) stereogenicity to generate chiral S(VI) scaffolds remains a largely underexplored challenge. Herein, we document a new activation mode of isothiourea organocatalysis for the highly enantioselective synthesis of S(VI)-chiral sulfonimidates. This method involves the covalent activation of racemic S(VI) sulfonimidoyl chlorides through the formation of a pivotal isothiourea-bound sulfonimidoyl intermediate.

Facile access to multi-substituted trifluoromethyl alkenes dehydroxyfluorination of 3,3-difluoroallyl alcohols.

The dehydroxyfluorination of allylic alcohols stands as one of the most direct and effective methods for synthesizing versatile allylic fluorides. However, regioselectivity control in this transformation remains challenging. Herein, we demonstrate a fluorine effect-induced regiospecific dehydroxyfluorination of 3,3-difluoroallyl alcohols using Olah's reagent under mild reaction conditions.

Visible-Light-Induced sp C-H Functionalization of Alkyl Amines toward Tetrahydroquinoline Spiro[5.6] Compounds.

An efficient and green methodology for the synthesis of tetrahydroquinoline spiro[5.6] compounds by visible-light-induced sp C-H functionalization reactions of alkyl amines has been developed. The advantages of this protocol include inexpensive photocatalysts, high diastereoselectivity, transition-metal-free properties, and wide-scope substrates.

Radial-Hierarchical Chromatomimetic E-Nose for Spatiotemporal VOC Diffusion Mapping.

This study introduces a radial-hierarchical, diffusion-enhanced spatiotemporal sensing paradigm for volatile organic compound (VOC) analysis via an integrated microchamber paper-based chromatomimetic e-nose. The proposed system synergizes interlayer spatiotemporal dynamics with planar spatial variance by employing a radially symmetric electrode array and a hierarchical porous chemoresistive ink (CuP@G). This design leverages molecular diffusion gradients across the sensing plane, enabling precise discrimination of complex VOC mixtures through multidimensional "spatiotemporal fingerprints".

In-ex site selectivity: a novel mechanism for the controlled fabrication of hollow multi-shelled nanostructures.

Site selectivity is fundamental to fabricating complex nanostructures. Herein, we introduce "In-Ex site selectivity," a novel mechanism for regulating deposition on a liquid template containing internal solid particles. The selectivity dictates whether deposition occurs on the interior (In) solid surface or the exterior (Ex) surface of the liquid template.

Anode-Electrolyte Interfacial Fluorine-Hydrogen Bonding Engineering for Boosted Electrocatalytic Oxidation of Small Organic Molecules.

Ions are essential components in the anode-electrolyte interfacial microenvironment that significantly influence both the activity and the pathway of electrocatalytic molecular oxidation reactions. Nevertheless, most anions are generally considered inhibitory on electrocatalytic molecular (such as alcohols and amines) oxidation reactions due to their specific adsorption at the inner Helmholtz layer, negatively impacting the electrocatalytic performance. In contrast, we have found herein that fluorine ion (F) at the outer Helmholtz layer is capable of largely elevating the electrocatalytic activity and promoting the transformation of glyceric acid to lactic acid as the main product by fluorine-hydrogen bonding with water molecules, glycerol reactants, and glyceraldehyde intermediate during the glycerol oxidation reaction.

Iron-Catalyzed Radical Addition Reaction of Dehydroglycine with Aliphatic Carboxylic Acids.

Iron-catalyzed ligand-to-metal charge transfer (LMCT) processes have emerged as robust strategies for diverse organic transformations. Despite this potential, their application to addition reactions of C═N unsaturated bonds remains underexplored. Herein, we report an LMCT-enabled, photoredox/iron-catalyzed radical addition to dehydroglycine derivatives.

-Substituted Diaryliodonium Salts Enabled Aryne 1,2,4'-Trifunctionalization.

A novel 1,2,4'-trifunctionalization of arynes was accomplished using -substituted diaryliodonium salts through a unique [5,5]-sigmatropic shift followed by a thia-Fries rearrangement. This cascade transformation enables the sequential formation of both C-N and C-S bonds, while also achieving the synthetically challenging -selective C-C bond on the non-aryne aromatic ring.

Site-Specific Chemoselective Cyclization and Fluorogenic Modification of Protein Cysteine Residues: From Side-Chain to Backbone.

The selective modification of natural protein templates has emerged as a powerful tool for investigating the protein structure and function as well as for designing therapeutic bioconjugates. While significant progress has been made in modifying protein side chains and terminal groups, backbone modifications remain underexplored due to the inherent inertness of amide bonds and the challenge of achieving site specificity. Despite the critical role of the backbone in the protein function, its selective chemical modification under physiological conditions has proven to be difficult.