Catalytic asymmetric cycloadditions of reactive ketene intermediates provide new opportunities for the production of chiral heterocyclic molecules. Though known for over 100 years, ketenes still ...remain underexplored in the field of transition-metal (TM)-catalyzed asymmetric cycloadditions because (1) ketenes, as highly electron-deficient species, are possibly unstable to low-valence TMs (i.e., decarbonylation or aggregation) and (2) the conventional thermal synthesis of ketenes from acyl chlorides and amines may be incompatible with TM catalysis (i.e., reactive acyl chloride and amine hydrochloride byproducts). Herein, we detail the unprecedented asymmetric 4+2 cycloaddition of vinyl benzoxazinanones with a variety of ketene intermediates via sequential visible-light photoactivation and palladium catalysis. It is well demonstrated that the traceless and transient generation of ketenes from α-diazoketones through visible-light-induced Wolff rearrangement is important for the success of present cycloaddition. Furthermore, chiral palladium catalysts with a new, chiral hybrid P, S ligand enable asymmetric cycloaddition with high reaction selectivity and enantiocontrol.
Vinylcyclopropanes (VCPs) are commonly used in transition‐metal‐catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great ...significance in modern synthetic chemistry. Herein, a palladium‐catalyzed, visible‐light‐driven, asymmetric 5+2 cycloaddition of VCPs with α‐diazoketones is accomplished by switching the reactivity of the Pd‐containing dipolar intermediate from an all‐carbon 1,3‐dipole to an oxo‐1,5‐dipole. Enantioenriched seven‐membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52–92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo‐ and periselectivities.
By switching the reactivity of Pd‐containing dipolar intermediates from all‐carbon 1,3‐dipoles to oxo‐1,5‐dipoles, Pd‐catalyzed asymmetric 5+2 cycloadditions of vinylcyclopropanes (VCPs) with photogenerated ketenes are achieved. A variety of chiral seven‐membered lactone‐fused polycyclic molecules are produced with good reaction efficiency and selectivity.
Higher‐order cycloadditions, particularly 8+2 cycloadditions, are a straightforward and efficient strategy for constructing significant medium‐sized architectures. Typically, configuration‐restrained ...conjugated systems are utilized as 8π‐components for higher‐order concerted cycloadditions. However, for this reason, 10‐membered monocyclic skeletons have never been constructed via catalytic asymmetric 8+2 cycloaddition with high peri‐ and stereoselectivity. Here, we accomplished an enantioselective 8+2 dipolar cycloaddition via the merger of visible‐light activation and asymmetric palladium catalysis. This protocol provides a new route to 10‐membered monocyclic architectures bearing chiral quaternary stereocenters with high chemo‐, peri‐, and enantioselectivity. The success of this strategy relied on the facile in situ generation of Pd‐containing 1,8‐dipoles and their enantioselective trapping by ketene dipolarophiles, which were formed in situ via a photo‐Wolff rearrangement.
With the help of visible‐light irradiation and a chiral palladium catalyst, enantioselective 8+2 cycloaddition of vinyl carbomates and α‐diazoketones has been accomplished with high peri‐, chemo‐ and stereoselectivity. This protocol provides an unprecedented and straightforward route to 10‐membered monocyclic products bearing chiral quaternary stereocenters under extremely mild conditions (i.e., room temperature and 6 W blue LEDs).
Our field needs research simultaneously driven by theory and context that is both rigorous and relevant. This commentary has sought to propose a viable road map to explore the interplay between ...context and concept toward theory building in an applied area of research such as ours. This commentary discusses a three-step approach of conceptualizing the context, contextualizing the concept, and cross-fertilizing the context and concept to systematically explore the interaction between context and concept in the interest of theory building. Specific steps at each stage of the process are also discussed.
Galactic outflows are observed everywhere in star-forming disk galaxies and are critical for galaxy formation. Supernovae (SNe) play the key role in driving the outflows, but there is no consensus as ...to how much energy, mass, and metal they can launch out of the disk. We perform 3D, high-resolution hydrodynamic simulations to study SNe-driven outflows from stratified media. Assuming the SN rate scales with gas surface density gas as in the Kennicutt-Schmidt relation, we find that the mass loading factor, m, defined as the mass outflow flux divided by the star formation surface density, decreases with increasing gas as . Approximately gas 50 M pc−2 marks when m 1. About 10%-50% of the energy and 40%-80% of the metals produced by SNe end up in the outflows. The tenuous hot phase (T > 3 × 105 K), which fills 60%-80% of the volume at the midplane, carries the majority of the energy and metals in the outflows. We discuss how various physical processes, including the vertical distribution of SNe, photoelectric heating, external gravitational field, and SN rate, affect the loading efficiencies. The relative scale height of gas and SNe is a very important factor in determining the loading efficiencies.
Ring‐opening transformations of donor‐acceptor (D‐A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using ...substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium‐catalyzed highly diastereo‐ and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron‐withdrawing groups, a subset of D‐A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five‐membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In‐depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H‐bonding in stereocontrol.
Two palladium‐catalyzed asymmetric (3+2) cycloadditions of donor‐acceptor (D‐A) cyclopropenes bearing two different electron‐withdrawing groups were reported. Various chiral five‐membered oxa‐ and aza‐heterocycles were produced, and good yields and high stereoselectivities were obtained. The key to the success of this reaction is the remote stereoinduction through H‐bonding from chiral ligands.
DNA double-strand breaks （DSBs） are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced ...small RNAs （diRNAs） is produced from sequences around DSB sites. DiRNAs are associated with Argonaute （Ago） proteins and play an im- portant role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination （HR） and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with RadS1 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that RadS1 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mrell loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating RadS1 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote RadS1 recruitment and/or retention at DSBs to facilitate repair by HR.
PS microplastic particle (<5 mm) is an emerging contaminant of concern in aquatic and sediment systems with reported negative impacts on environmental and human health. TCS is a broad-spectrum ...antimicrobial which can affect ecosystems and result in long-term human health risks. The interaction between TCS and PS microplastic, partly determines the behavior and dispersion of TCS in the environment. In this study, the sorption kinetics and isotherms for TCS and PS microplastic were investigated. The influences of temperature, pH, ionic strength and coexisting heavy metals were assessed in batch experiments. The pseudo-second-order model (PSOM) was found to effectively describe the sorption kinetics of TCS on PS. TCS sorption on PS was found to be higher within the pH range of 3.0–6.0, while a decrease occurred at pH > 6.0. This result indicates that TCS0 was the major species contributing to the sorption process through hydrophobic interaction. Temperature did not affect the sorption of TCS on polystyrene, with sorption Kd values of 0.15, 0.16, 0.18 and 0.17 L/g at 288, 298, 308 and 318 K, respectively. Furthermore, the sorption amount of TCS showed no obvious variation with NaCl concentrations varying between 0.001 and 0.1 M. Finally, the coexistence of Cu(II)/Zn(II) had no significant influence on TCS sorption on PS, as Cu(II)/Zn(II) and TCS had different mechanisms of sorption on PS.
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•Triclosan (TCS) sorption on Polystyrene (PS) microplastic was assessed.•The sorption capacity of TCS increased with decreasing particle size of PS.•pH value plays an important role in the sorption of TCS on PS microplastic.•Hydrophobic interaction is the main mechanism of TCS sorption on PS.•Temperature, ionic strength and Cu(II)/Zn(II) had no effect on TCS sorption.
An enantioselective 5+2 cycloaddition of vinylethylene carbonates and α-diazoketones was achieved for the first time by merging photoactivation and asymmetric Pd catalysis. The key to the success of ...this method is the enantioselective trapping of Pd-containing, 1,5-dipolar intermediates by ketenes, a class of reactive C2 synthons, which were generated in an in situ and traceless manner under visible light irradiation. Through this trapping, a variety of 7-membered lactones bearing challenging chiral quaternary stereocenters can be accessed in a facile manner with good efficiency and high enantioselectivity (up to 99% yield and 96:4 er).
Conspectus Fluorescent probes have become powerful tools in detection, imaging and disease diagnosis due to their high sensitivity, specificity, fast response, and technical simplicity. In the last ...decades, researchers have made remarkable progress in developing signaling mechanisms to design fluorescent probes such as photoinduced electron transfer (PET), intramolecular charge transfer (ICT), and fluorescence resonance energy transfer (FRET). Typical PET is composed of a multicomponent system in which a fluorophore (electron acceptor) is separately linked with a recognition group (electron donor) via a short spacer. PET probes normally feature a low fluorescence background and significant fluorescence enhancement in response to targets. Recent research revealed that PET probes have also been used as theranostic agents, whose fluorescence and toxicity can be simultaneously activated by cancer-specific parameters. In this Account, we highlight the recent advances of rational design and applications of PET probes, focusing primarily on studies from our research group. For example, different from the case of the traditional single-atom electron donor (O, S, N, Se, Te, etc.) in typical PET, we used more a electron-rich pyrrole ring to “switch off” the fluorescence of the fluorophore more efficiently through an “enhanced PET” effect which provided a lower background fluorescence and higher signal-to-noise ratio. Furthermore, normal PET represents the main principle behind the design of small molecule “off–on” fluorescent sensors. We developed new PET platform through intramolecular space folding (folding PET) to overcome the difficulty of designing PET enzyme-targeting probes. Therefore, based on typical PET and these new PET concepts, we, for instance, reported PET probes for the detection of Zn2+ without proton interference, a BODIPY-based d-PET probe for reporting local hydrophilicity within lysosomes, and an “enhanced PET” fluorescent probe for imaging HClO in cancer cells. We also developed COX-2-specific probe for identifying cancer cells and quantifying cancer-related events, and a KIAA1363-sensitive probe for tracking solid tumors in living mice. Furthermore, we first applied an aminopeptidase N (APN)-sensitive probe based on PET for cancer diagnosis and therapy. We anticipate that further development of PET fluorescent probes providing more sensitivity and selectivity to analytes of interest will be equipped with more functions and play indispensable roles in the studies of pathology, diagnostics, and cancer therapies.
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