Long emission lifetime is the defining character of organic room-temperature phosphorescence (RTP) and afterglow materials. In the absence of heavy atom effect, organic localized excitation (LE) systems show small phosphorescence rates and exhibit potential to form long-lived phosphorescence materials. However, such LE systems usually have limited population of T1 states because of large singlet-triplet splitting energy (Delta EST, around 1 eV). Here we report ultralong RTP by balancing intramolecular charge transfer and localized excitation character of excited states. Aromatic functional groups of moderate electron-donating strength are selected to build difluoroboron beta-diketonate (BF2bdk) systems with moderate intramolecular charge transfer (ICT) character in their S1 states. Such molecular design gives rise to Delta EST around 0.5 eV and is enough to populate BF2bdk's T1 states. Significantly, the resultant BF2bdk's T1 states exhibit 85-90% 3LE character and display long phosphorescence lifetimes up to 1.38 s upon doping under ambient conditions. This study shows that simple design of organic system can also lead to high-performance RTP materials and provide an insight into the fundamental photophysics of organic triplet system.

9,10-Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10-secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase-like 3-ketosteroid 9 alpha-hydroxylase (KSH) as the biocatalyst to achieve efficient C9-C10 bond cleavage and A-ring aromatization of tetracyclic steroids through 9 alpha-hydroxylation and fragmentation. With synthesized 9,10-secosteroides, structure-activity relationship was evaluated based on bioassays in terms of previously unexplored anti-infective activity. This study provides experimental evidence to support the hypothesis that the biosynthetic pathway through which 9,10-secosteroids are formed in nature shares a similar 9 alpha-hydroxylation and fragmentation cascade. In addition to the development of a biomimetic approach for 9,10-secosteroid synthesis, this study highlights the great potential of chemoenzymatic strategies in chemical synthesis.

A Ni-catalyzed enantioselective hydroamination of vinylarenes has been developed, affording a wide variety of alpha-branched chiral alkylamines in good yields with exclusive Markovnikov regioselectivity and excellent enantioselectivity. The SKP ligand was found to be crucial to both the reactivity enhancement and enantiocontrol of the reaction. The synthetic utility of the protocol was exemplified in a gram-scale reaction and late-stage modification of medicinally relevant molecules. The deuterium-labeling experiment revealed that the irreversible hydronickelation of vinylarenes is most likely the enantioselectivity-determining step.

A catalyst-free intermolecular dearomatization reaction of beta-naphthols with hypervalent-iodine-based nitrooxylating reagent is reported. Various nitrooxylated beta-naphthalenones bearing a quaternary carbon stereogenic center were obtained smoothly in good to excellent yields (up to 87 %) under mild conditions. This method features mild conditions, broad substrate scope and excellent chemoselectivity.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry. This minireview article highlights the role of sulfur in enhancing sustainable carbon-carbon coupling reactions for emerging organic synthesis goals. A unique combination of sulfur properties is emphasized for initiating radical transformations and facilitating waste-free processes, offering significant advancements and new eco-friendly synthesis directions. image

We report here an asymmetric carboxylation reaction based on kinetic resolution of tertiary propargylic alcohols by identifying Pd((R)-DTBM-SEGphos)Cl2 as the pre-catalyst. A variety of optically active tertiary propargylic alcohols and tetrasubstituted 2,3-allenoic acids were obtained in good yields with excellent enantioselectivities. The salient features of this report include the use of readily available substrates, a readily available precatalyst, mild reaction conditions, remarkable functional group tolerance, gram-scale synthesis, and versatile synthetic transformations. Mass spectrometry experiments trapped some key intermediates, which revealed the mechanism.

The unprecedented copper-catalyzed asymmetric alkynylallylic monofluoroalkylation reaction is described via the use of 1,3-enynes and fluorinated malonates. A series of 1,4-enynes bearing a monofluoroalkyl unit are achieved in high yields, excellent regio- and enantioselectivity and high E/Z selectivity. The asymmetric propargylic monofluoroalkylation is also developed. The reliability and synthetic value of the work are highlighted by a gram-scale test and a couple of downstream transformations. Preliminary mechanistic studies unveil a negative nonlinear effect for the catalytic process. 1,4-Enyne bearing a monofluoroalkyl unit is achieved in a high yield and stereoselectivity via Cu-catalyzed asymmetric alkynylallylic monofluoroalkylation.

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9 alpha-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1 beta-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5 alpha-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol. Despite intensive investigation, stepwise reactions from diol to Taxol tetracyclic core skeleton remain unclear. Here, authors fill this gap by identifying two P450s and confirming the reaction order.

The development of semiconducting polymers (SPs) with simultaneous second near-infrared (NIR-II) absorption and multimodal phototheranostic functions is highly desired in the field of oncotherapy. Aggregation-induced emission luminogens (AIEgens) have been acknowledged to possess unique potential in integrating multiple diagnostic and therapeutic modalities into one organic molecule. Nevertheless, SPs are hard to achieve AIE activity due to their extended pi-conjugated skeletons as well as the large and planar configuration of commonly-used electrophilic acceptor moieties. Herein, an ingenious acceptor dimerization-based acceptor distortion strategy is proposed in current work by taking advantage of the sterically encumbered acceptors with large and planar structure for the successful construction of AIE-active SPs. Through further finely adjusting the molecular donor-acceptor interaction strength, one of the obtained AIE-active SPs named SP3 bearing the highest intramolecular charge transfer effect presented desired NIR-II absorption and aggregation-induced NIR-II fluorescence emission, good reactive oxygen species production ability, as well as superior photothermal conversion performance. Accordingly, SP3 is selected to fabricate into nanoparticles and successfully applied in the NIR-II laser-triggered fluorescence-photoacoustic imaging-guided photodynamic-photothermal therapy of tumors. This study represents the first NIR-II excitable AIE-active SP, and offers a new perspective on designing advanced multimodal phototheranostic polymers for efficient treatment of malignant tumor. A novel acceptor dimerization-based acceptor distortion strategy by taking advantage of the sterically encumbered acceptors with large volume and planar structure is proposed, through which the first NIR-II excitable and AIE-active SP with all of the phototheranostic features including NIR-II laser-triggered fluorescence-photoacoustic imaging and photodynamic-photothermal therapy is ingeniously reported. image

Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain-derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau-inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.

Ethylene/alpha-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/alpha-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and alpha-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and alpha-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces. Although several advances have been made in chemical Polyethylene (PE) re- and upcycling, energy-efficient and selective catalytic processes are still lacking. Here, the authors show coupling of an industrially relevant coordination copolymerization olefins with a functionalized chain-transfer agent, followed by modular assembly of the resulting telechelic polyolefin building blocks by polycondensation to afford ester-linked PE-based random and block copolymers which exhibit full chemical circularity.