Stereogenic-at-P(V) skeletons exist ubiquitously in drugs, agrochemicals, organocatalysts, ligands and materials. Conventional synthetic methods mainly rely on chromatographic resolution, chiral auxiliary induction and optically active substrate control. Catalytic asymmetric transformation as an economic pathway has received much progress via racemic substrate resolution and desymmetrization of prochiral precursors. Among them, catalytic desymmetric substitution strategy has recently emerged as a new and powerful route to construct P(V) stereocenter, particularly witnessed a series of achievements in preparing seldom studied fully heteroatom-substituted P(V) scaffolds in the past one year. This minireview aims to provide a timely summary and highlight on this rapidly developing field, including reaction design, synthesis, mechanism and applications, and also perspective on the potential limitations and future trend.

Metal carbenes have long been recognized as a pivotal reactive intermediate in organometallic chemistry. Recently catalytic reductive processes with gem-dichloroalkanes have emerged as a promising strategy to generate nonstabilized donor carbenes for alkene cyclopropanation. However, the catalytic cycle remains challenging to study largely due to the inherent instability of metal carbene intermediates. In this study, we elucidated an ECEC mechanism for the (PNN)Co-catalyzed (PNN = bipyridyl phosphine) reductive cyclopropanation of alkenes through an integrated experimental-computational approach combining electroanalytical techniques and density functional theory (DFT) calculations. Initiated by ZnCl2-assisted one-electron reduction of (PNN)CoIICl2 (1) to [(PNN)center dot-]CoIICl (2) featuring a reduced pi-radical anion, activation of aryl gem-dichloromethanes by 2 proceeds via outer-sphere electron transfer (OSET) as determined by Hammett linear free-energy relationship (LFER) analysis, producing a cationic benzyl Co(III) species [(PNN)CoIIICl(benzyl)]+ZnCl3 - (A). Following the first EC, cyclic voltammetry studies, controlled potential electrolysis, and reactivity comparison experiments collectively established the second EC process involving one-electron reduction of A to a cationic Co(II) carbene [(PNN)CoIICl(carbene)]+ZnCl3 - (C) that is effective for the following carbene transfer. LFER analysis and computational data support the assignment of intermediate C as an electrophilic Co(II) carbene, rationalizing a concerted, nonradical addition pathway for cis-selective alkene cyclopropanation. This work provides a multielectron, multistep mechanistic framework, which could be valuable for developing sustainable catalytic transformations that employ base metals.

Natural products continue to play a pioneering role in drug discovery due to their extraordinary chemical and biological diversity. However, their full therapeutic potential remains largely underutilized, hindered by the fragmented documentation of biological origins in existing data resources. Here, we present natural product and biological source atlas (NPBS Atlas), a data resource covers over 218,000 natural products fully annotated with comprehensive biological sources, bioactivities, and references. The database established through systematic text mining and expert manual curation, places special emphasis on curating source organism data through the information of scientific nomenclature, taxonomic classification, source parts, and the source of Traditional Chinese Medicines. NPBS Atlas represents significant advancement in natural product data resources through its unique content, specialized annotations, and featured data, thereby enabling unprecedented exploration of nature-derived chemical diversity through biological context. The web interface of NPBS Atlas is freely available at https://biochemai.cstspace.cn/npbs/.

Two supramolecular organic frameworks (SOFs) have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water. Dynamic light scattering and 1 H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature. One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice, which improves by 40 % compared with the highest value of the reported SOFs. In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery, leading to enhanced antitumor efficacy. Moreover, it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism. As the first examples that undergo room-temperature reversible assembly and disassembly, the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The sulfenylative N-glycosylation of glycals, which exhibits high beta-stereoselectivity, has been successfully developed for the first time under the facilitating effect of hexafluoroisopropanol (HFIP). This method is broadly applicable to four classes of nitrogen nucleophiles, including sulfamides, carbamates, ureas, and azoles. Furthermore, various glycal derivatives, such as D-galactal, D-arabinal, L-fucal, and D-glucal, can be effectively employed in this reaction system. A range of 2-phenylthio-N-glycosides were obtained in moderate to good yields with consistently high beta-selectivity (beta:alpha > 20:1). Density functional theory (DFT) calculations reveal the origin of the observed stereoselectivity and highlight the critical role of HFIP in promoting the glycosylation process.

Inactivation of cyclin-dependent kinase 12 (CDK12) defines an immunogenic molecular subtype of prostate cancer characterized by genomic instability and increased intratumoral T cell infiltration. This study revealed that genetic or pharmacologic inactivation of CDK12 and its paralog CDK13 robustly activates stimulator of interferon genes (STING) signaling across multiple cancer types. Clinical cohort analysis showed that reduced CDK12/13 expression correlates with improved survival and response to immune checkpoint blockade (ICB). Mechanistically, CDK12/13 depletion or targeted degradation induced cytosolic nucleic acid release, triggering STING pathway activation. CDK12/13 degradation delayed tumor growth and synergized with anti-PD-1 therapy in syngeneic tumor models, enhancing STING activity and promoting CD8+ T cell infiltration and activation within tumors. Notably, the antitumor effects of this combination required STING signaling and functional CD8+ T cells. These findings establish STING activation as the key driver of T cell infiltration and the immune-hot tumor microenvironment in CDK12-mutant cancers, suggesting that dual CDK12/13 inhibitors and degraders activate antitumor immunity and potentiate responses to immunotherapies.

Polymer nanostructures with controlled morphology and tunable chiroptical activities of circular dichroism (CD) and circularly polarized luminescence (CPL), showing promising applications ranging from information encryption to display, have attracted growing interest. However, their facile and precise preparation remains a great challenge. In this contribution, we report a chiral bisammonium-directed crystallization-driven self-assembly strategy to generate uniform ribbon-like micelles of controlled length and tunable CD and CPL spectra. By a heating-cooling protocol, the CDSA of crown ether-terminated OPV4 and OPV5 (OPV = oligo(p-phenylenevinylene), where the subscript represents the number of repeat units) gave ribbon-like micelles with lengths up to tens of micrometers and widths up to hundreds of nanometers. The bisammonium was supposed to act as a bridge and form a sandwich-like complex with two crown ethers at two adjacent OPV chain ends. Owing to the chiral structure of bisammonium and the ordered packing of OPV units, chiral bisammonium with a relatively rigid conformation would induce slight twisting of OPV units, which endowed the resulting ribbon-like micelles with tunable CD and CPL properties, with a high g lum (dissymmetry factor) value up to the order of 10-2. More importantly, it was found that the chiral bisammonium can serve as a bridge between two adjacent crown ether chain ends of two separate OPV units to enhance the affinity of free unimers to the ends of seed micelles. This bridge effect not only promoted the efficiency of seeded growth to give uniform fiber-like micelles in a controlled way but also directed the packing of OPV4-18C6 to endow the resulting micelles with chiroptical properties. Since the CPL property of the resulting OPV4-18C6-based nanostructures can be regulated by the chirality of bisammoniums, proof-of-concept anticounterfeiting materials can be fabricated from the CDSA of OPV4-18C6 with different chiral bisammoniums. Given the robustness of (living) CDSA and the great variety of noncovalent interactions, the concept of noncovalent-interaction-directed CDSA can be extended to other polymer systems to create diverse nanostructures with controlled dimensions and tunable CD and CPL properties.