Aqueous foams featuring near-zero calory properties not only form the basic textural matrix of fluffy textured foods but also create substantial emotional and esthetic excitement. However, edible aqueous foams stabilized by food-grade biomolecules typically have a lifetime of less than several minutes due to capillary pressure-driven disproportionation and coalescence with water drainage. In this study, we propose a complex of protein nanoparticles and starch nanocrystals synergistically diffusing to the air-water interface and reinforcing the interface film. The regulated amphiphilicity of the protein-nanocrystal complexes enabled preferential absorption and stabilization of the interface, while the hydrophilic nature of starch nanocrystals promoted water trapping amongst the bubble interspace. As a result, the half-lifetime of the aqueous foams was greatly lengthened by 23 times, i.e., from 30 min to 12 h. This study advanced the stabilization of aqueous foams toward food-oriented applications with fundamental implications for producing next-generation low-calory and fluffy textured foods.

We present the synthesis and host-guest complexation of endo-functionalized shape-persistent hexa(ethynylpyridine) macrocycles (Py6 MCs). The challenging macrocyclization of linear hexapyridine precursors was achieved by using catalytic amount of PdCl2 (PPh3 )2 and stoichiometric CuI in the Sonogashira reaction, or with K2 CO3 as an additive under copper-free conditions. Single-crystal X-ray diffraction revealed that Py6 MCs with different side chains all feature a near-planar framework, with notable flexibility to adopt chair-like or boat-like conformations. The polar and electron-rich cavities of Py6 MCs render them attractive hosts for cationic guests. 1 H NMR and fluorescence titrations showed that Py6 MC1 and Py6 MC2 formed 1:1 complexes with N -methyl pyridinium and quaternary ammonium cations, and high affinity (up to 3.1 & times; 105 L/mol) was achieved for cations of distinct shapes and sizes. Density functional theory (DFT) calculations showed that Py6 MC readily deforms to complement the structures of different guests, demonstrating a high level of adaptivity. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

We developed a photoredox–cobalt synergistic biomimetic reaction, constructing an unsaturated molecular library. Remarkably, we demonstrate the synthesis of a series of polysubstituted cinnamaldehydes. Furthermore, reported an unprecedented property of α‑fluoroalkyl compounds, defluorination was absent in the presence of a cobaloxime catalyst or vitamin B12, but pronounced without cobalt catalyst. This revealed the catalytic commonality

Energy transfer (EnT) photocatalysis provides access to excited-state reactivity beyond thermal processes, yet highly enantioselective cycloadditions of sulfonamide-containing substrates remain challenging. Here we report a cofactor engineering strategy that reprograms glutathione S-transferases (GSTs) into artificial photoenzymes for enantioselective intramolecular [2 + 2] photocycloadditions to furnish chiral bicyclic sultam scaffolds. A photoactive glutathione-derived cofactor bearing a benzophenone photosensitizer (GS-Bp1) is prepared and reversibly assembled within GST scaffolds through native cofactor-like molecule-protein interactions. Screening and directed evolution of human GST A1-1 yield an optimized artificial photoenzyme that delivers a range of bicyclic sultams with moderate to excellent yields and enantioselectivities (up to 99% ee and up to 480 TONs), surpassing small-molecule benzophenone photocatalysts by more than 2 orders of magnitude in efficiency. Combined spectroscopic and computational studies reveal that directed evolution enhances stereocontrol by rebalancing π-π stacking and dispersion interactions in the transition state. Together with our previous NAD+-derived artificial cofactor systems, this work establishes cofactor engineering as a general strategy for reprogramming native protein families using canonical cofactors or cofactor-like molecules, enabling enantioselective photochemical transformations beyond those found in nature.

Selective activation of aliphatic C-H bonds in polycyclic terpenoids offers a potent strategy for exploring diverse chemical space in drug design, yet challenges persist in achieving site- and diastereoselectivity, especially with increasing structural complexity. Here we report a bioinformatics-driven terpene-P450 discovery strategy to develop bacterial cytochrome P450s for selective activation of aliphatic C-H bonds in structurally intricate pentacyclic triterpenoids (PTs). The identified ApPT demonstrated elegant diastereoselectivity and broad substrate tolerance, facilitating a chemo-enzymatic platform to explore the chemical space of PTs at previously inaccessible sites. Protein crystallization and computational analysis reveal the mechanism of the preliminary C-H bond activation selectivity of ApPT towards various PTs, particularly an example of enzymatic C7-to-C15 relay oxidation mediated by 1,5-hydrogen atom transfer. This work offers ApPT as a valuable biocatalyst to explore the chemical space of PTs via aliphatic C-H bond activation, demonstrating the advantage of our biocatalyst-discovery strategy for the late-stage diversification of polycyclic terpenoids.

In drug discovery, the pursuit of concise and specific synthetic methods is driving the development of new strategies. Particularly during the late stages of a synthetic sequence, when the substrate molecule contains multiple highly similar C-H bonds, the ability to achieve selective "molecular editing" using mild and precise transformations has become a crucial capability. Here, we report Rh-catalyzed molecular editing of indoline derivatives at different positions via a single, oxidant-tunable catalytic system. Using Ag3PO4 as the oxidant, Rh promotes the formation of indoline radical cations stabilized by SbF6 -, enabling remote C5 thiolation via a single-electron transfer (SET) mechanism, as supported by the Fukui function. In contrast, Ag2O suppresses the SET pathway, as confirmed by the ABTS assay, and enables C7-selective thiolation through a concerted metalation-deprotonation (CMD) process mediated by a Rh(III)/MPAA ligand system. Mechanistic experiments and Fukui indices calculation elucidate the origin of the observed regiodivergence, highlighting the dual reactivity of Rh(III) and offering new conceptual insights into oxidant-controlled C-H functionalization.

Precise control of cell-surface glycosylation remains challenging due to the dynamic and spatially complex nature of glycans. Here, we present GLOBE, a platform for optical regulation of glycoenzyme activity via site-specific incorporation of photocaged unnatural amino acids. Using galactose oxidase (GAO) as a model, o-nitrobenzyl-tyrosine (ONBY) installed at a proximal tyrosine suppresses activity until photoactivation, enabling rapid cell-surface glycan oxidation with micrometer-scale spatial and temporal resolution. Coupling GAO with MUC1-targeting aptamer produces binding-gated, protein-selective glycan oxidation, achieving precise control in mixed cellular populations. GLOBE is further extended to in situ suppression of a sialidase catalytic domain, and integrated into an orthogonal photoresponsive cascade, where sialic acid removal exposes substrates for subsequent GAO oxidation, enhancing labeling efficiency. Finally, upconversion nanoparticle-assisted photoactivation enables in vivo glycan editing in a murine tumor model, overcoming UV tissue penetration limits. Together, GLOBE provides a modular, spatiotemporally programmable framework for probing and manipulating dynamic glycosylation at single-cell and tissue levels, offering a versatile strategy to interrogate and engineer the complex sugar code underlying biological and pathological processes.

Controlling the regioselectivity in C-H functionalization is a challenging issue in organic synthesis. Typically, the specific electronic and/or steric character of the substrate leads to intrinsic site selectivity in C-H functionalization. While enhancing intrinsic site selectivity is relatively straightforward, altering and reversing high selectivity is challenging. By the use of a designed ligand for an iridium catalyst, the normally preferred para-selective C-H borylation of sulfated phenol and aniline derivatives has been completely inverted to strong meta-selectivity. This protocol affords a variety of meta-borylated phenols, anilines, and related compounds with excellent regioselectivity under mild reaction conditions. Mechanistic experiments and density functional theory calculations elucidate the origins of this conversion from para- to meta-selectivity.

Despite the inherent competition between cyclization and linear polymerization, we report the exclusive synthesis of a macrocyclic trimer from 1,2,3,4-tetramethoxybenzene and paraformaldehyde. Dynamic Friedel-Crafts alkylation proceeds solely through linear oligomeric intermediates, which ultimately convert to the cyclic trimer without polymer formation. NMR monitoring tracks this stepwise conversion, and DFT studies identify the cyclic trimer as the thermodynamically favored product among accessible species. This system circumvents the cyclization-polymerization equilibrium, providing insight into the competition mechanism under macrocycle synthesis.

ABSTRACT Achieving regioselective C–H functionalization is a particularly difficult issue in organic chemistry when these C–H bonds have similar reactivity. Although significant progress has been made in regioselective C–H functionalization at one specific site, the tunable version of such processes is rarely documented. Here we describe a tunable meta ‐ and para ‐selective C–H borylation of aryl and benzyl phosphonates, in which the regioselectivity can be switched by bifunctional ligands. A broad range of substrates are compatible and exhibit good to excellent regioselectivity under mild reaction conditions. Benzyl phosphonates can be conveniently transformed into styrene derivatives via Horner–Wadsworth–Emmons olefination. Gram‐scale preparation and derivatization of borylated products demonstrate the important application of our method in synthetic chemistry. The orthogonality of two functional Bpin and phosphorylmethyl groups provides ample opportunity for increasing the diversity of styrene derivatives with precise site‐control.

The synthesis of nitrogen heteroarenes has a rich history, including many illustrious name reactions. These reactions often involve complex oxidative processes or the need for transition metal catalysts, and the synthesis of different N-heteroarenes typically requires a case-by-case approach. Here, we have discovered the conversion of vicinal alkyl and nitro groups on arenes or alkenes into an array of N-heteroarenes, including indoles and pyrroles. Moreover, our approach also facilitates the synthesis of benzimidazoles from ortho NH-alkyl nitroarenes. This versatile method leverages a redox-neutral aromatization and CO reduction sequence, uniquely utilizing Cs2CO3, and is remarkable for its omission of any transition metals. Our strategy is particularly noteworthy for its exceptional atom, step, and redox efficiency, offering significant advantages for the synthesis of alkaloids that are important in pharmaceutical applications. Extensive experimental and computational studies have allowed us to understand the preferred mechanistic pathways for these heteroarene formations.

The synthetic utility of alkyne metathesis remains underdeveloped compared to olefin metathesis, its mechanistic analogue. Advancement in tridentate molybdenum alkylidyne catalysts led to an expanded substrate scope and enhanced stability. However, the systematic tuning of their steric and electronic properties has not yet been realized. Here, we report a library of adaptive tridentate ligands with a tris(biphenyl)methane backbone. A total of 35 ligands were prepared using a modular synthetic strategy, all of which were active in metathesis upon ligand exchange with a precatalyst cat-II, and 12 of them demonstrated activity surpassing that of the fastest monodentate and tridentate ligands in literature. Density functional theory (DFT) calculations suggested that their reactivity originated from the highly adaptive ligand backbone, which could accommodate different coordination geometries with minimal strain. A systematic survey established that steric factors outweigh electronic properties, and the highest reaction rates were achieved for ligands with medium-sized meta-substituents or bulky para-substituents. The catalysts demonstrated moderate stability and retained full activity after 2 h of open vial storage in air. Anthraquinone-bearing L-CP21 features a rather broad substrate scope, promoting the metathesis of challenging substrates bearing cyano, nitro, aldehyde, aniline, pyridine, and pyrimidine groups with excellent isolated yields.

Chiral rotaxanes have attracted considerable attention due to their distinctive properties resulting from their unique mechanically interlocked structures. However, the construction of chiral rotaxanes based on the dynamic racemic pillar[5]arene (DMP5A) by induction remains uncharted territory. In this study, we provide a method for synthesizing chiral rotaxanes based on DMP5A via an axle-cycle induction strategy. Amino acid derivatives serve as both chiral axles and chiral inducers for DMP5A, enabling the diastereoselective construction of chiral [2]rotaxanes. This axle-cycle induction strategy not only offers a synthetic method for DMP5A-based chiral rotaxanes with stereochemical control but also provides a foundation for chiral stationary-phase high-performance liquid chromatography (HPLC)-free (CSP-free) synthesis of mechanically interlocked molecules.

Terpenoids represent the most structurally diverse class of natural products on Earth. Terpene synthases are key enzymes for constructing the complex and varied terpene skeletons by catalyzing the formation of multiple carbon-carbon bonds. Phomactatriene and verticillene family natural products are both classified as bicyclic diterpenoids, sharing a unique bicyclo[9.3.1]pentadecane skeleton. In this study, we used genome mining to identify the phomactatriene synthase SiPS from bacteria, together with two verticillene synthases, LxVS and AxVS. Our DFT calculations revealed that the rearrangement pathways for compounds in the phomactatriene and verticillene families follow a shared biosynthetic route. Furthermore, through comparative structural model analyses of the phomactatriene and verticillene synthases, we employed molecular modelling and site-directed mutagenesis to facilitate functional interconversion between these distinct terpene synthases. This work enhances our understanding of terpene biosynthesis and the potential for engineering terpene synthases for biotechnological applications.

Through DFT and NCI analysis, we designed a bulky tertiary phosphine directing group, enabling an iridium-catalyzed C6-selective borylation of indoles with a simple and commercially available ligand, 1,10-phenanthroline. The directing group has dual dispersive interactions with both phenanthroline and a Bpin group, which enhance selectivity and reactivity.

Co‐catalyzed C─H borylation of arenes has drawn great attention in organic chemistry, in which the system using terpyridine (tpy) ligands stands out due to its bench stability and synthetic accessibility. However, despite its experimental breakthrough, it remained largely unexplored from a theoretical standpoint. In this work, we present a comprehensive theoretical investigation into the cobalt‐catalyzed C─H borylation of arenes using terpyridine as ligand. Our computational analysis reveals the overall mechanism involving stages as C─H activation, C─B formation, and catalyst regeneration, with C─H activation identified as the rate‐determining step. Furthermore, we attempt to address the reactivity issue, the key challenges faced by this system, including potential catalyst deactivation mechanisms and comparative analysis with other related catalytic systems.

Anthracyclines featuring a tetracyclic (A-D rings) scaffold, such as clinically approved doxorubicin and aclarubicin, are essential natural products. The D-ring presents an intriguing structural puzzle: while predominantly nonaromatic and typically decorated with one or two alpha-oriented oxygenated substituents, its aromatization constitutes a critical biosynthetic prerequisite for the conversion of resomycin C into chartreusin, a promising antitumor drug candidate. Given the intriguing and biologically significant nature of the "D-ring state", we elucidate here the mechanism of D-ring aromatization during resomycin C biosynthesis. This process features an unprecedented dehydration pattern mediated by the collaborative catalysis of two enzymes, ChaU and ChaX. Combining gene inactivation, biochemical assays, isotope labeling, protein crystallography, and site-directed mutagenesis, we demonstrated that ChaU facilitates the stereoselective C2-C19 cyclization and plays a critical role in prompting the attack of water on C17 from the pro-R face, followed by the 17-dehydroxylation mediated by ChaX, thereby triggering the aromatization of the D-ring. Furthermore, molecular dynamics simulations and density functional theory calculations elucidated the stepwise catalytic mechanism of the ChaU/ChaX-mediated cascade reactions that drive D-ring aromatization, uncovering a previously unrecognized dehydration pathway. Collectively, this work reveals sophisticated enzymatic strategies for anthracycline biosynthesis, enabling a more rational biotechnological production of valuable anthracyclines.

The C-H bond functionalization has been widely used in chemical synthesis over the past decade. However, regio- and stereoselectivity still remain a significant challenge, especially for inert aliphatic C-H bonds. Here we report the mechanism of three Fe(II)/α-ketoglutarate-dependent dioxygenases in bicyclomycin synthesis, which depicts the natural tactic to sequentially hydroxylate specific C-H bonds of similar substrates (cyclodipeptides). Molecular basis by crystallographic studies, computational simulations, and site-directed mutagenesis reveals the exquisite arrangement of three enzymes using mutually orthogonal strategies to realize three different regio-selectivities. Moreover, this programmable selective hydroxylation can be extended to other cyclodipeptides. This evidence not only provides a naturally occurring showcase corresponding to the widely used methods in chemical catalysis but also expands the toolbox of biocatalysts to address the regioselective functionalization of C-H bonds.

Bioorthogonal chemistry has emerged as a powerful tool for the development of controllable drug delivery systems. Bioactive sulfur species, which participate in complex sulfur signaling pathways, play crucial roles in various physiological and pathological processes. However, achieving precise and controlled administration of these sulfur species remains challenging due to their unique physicochemical properties. Over the past few years, a growing number of delivery strategies, which are triggered by different stimuli, have been developed to enhance our understanding of sulfur signaling. Bioorthogonal triggers not only offer excellent controllability but also provide advantages such as tunability, targeted delivery, and spatiotemporal feedback. This review highlights representative donors that can be activated through bioorthogonal reactions and their applications in studying the biological mechanisms and therapeutic functions of the bioactive sulfur species.