Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal‐free ...regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α‐branched, and α‐tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.
A straightforward and modular route to a wide variety of aliphatic primary amines from alkenes is presented based on a metal‐free hydroamination at room temperature. The use of cost‐effective and easily available ammonium carbonate allows for the efficient conversion of terminal and internal alkenes with diverse substitution patterns into highly functionalized linear, α‐branched, and α‐tertiary primary amines.
Lithium–sulfur (Li–S) batteries are regarded as promising high‐energy‐density energy storage devices. However, the cycling stability of Li–S batteries is restricted by the parasitic reactions between ...Li metal anodes and soluble lithium polysulfides (LiPSs). Encapsulating LiPS electrolyte (EPSE) can efficiently suppress the parasitic reactions but inevitably sacrifices the cathode sulfur redox kinetics. To address the above dilemma, a redox comediation strategy for EPSE is proposed to realize high‐energy‐density and long‐cycling Li–S batteries. Concretely, dimethyl diselenide (DMDSe) is employed as an efficient redox comediator to facilitate the sulfur redox kinetics in Li–S batteries with EPSE. DMDSe enhances the liquid–liquid and liquid–solid conversion kinetics of LiPS in EPSE while maintains the ability to alleviate the anode parasitic reactions from LiPSs. Consequently, a Li–S pouch cell with a high energy density of 359 Wh kg−1 at cell level and stable 37 cycles is realized. This work provides an effective redox comediation strategy for EPSE to simultaneously achieve high energy density and long cycling stability in Li–S batteries and inspires rational integration of multi‐strategies for practical working batteries.
A redox comediation strategy is proposed for promoting the cathode redox kinetics and simultaneously retaining the anode protection capability of lithium–sulfur batteries using encapsulating lithium polysulfide electrolyte. A 1.5 Ah lithium–sulfur pouch cell realizes a high initial energy density of 359 Wh kg−1 and 37 stable cycles following the above strategy.
Chiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate ...between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance.
Adding to the super-resolution arsenal
Structured illumination microscopy (SIM) uses light intensities that are orders of magnitude lower than other super-resolution methods. SIM is also far faster ...over cellular-sized fields of view. Li
et al.
used two approaches to improve the resolution of SIM to allow live cell imaging of dynamic cellular processes, including endocytosis and cytoskeleton remodeling. The contrast in performance between SIM and other techniques is due to a few key differences. Defining the practical resolution at the limited signal-to-noise ratios necessary for live cell imaging will require better imaging metrics.
Science
, this issue
10.1126/science.aab3500
Super-resolution imaging of fast dynamic processes in living cells is facilitated by improvements to structured illumination microscopy.
INTRODUCTION
Various methods of super-resolution (SR) fluorescence microscopy have the potential to follow the dynamic nanoscale interactions of specific macromolecular assemblies in living cells. However, this potential is often left unfulfilled, either owing to the method’s inability to follow these processes at the speeds dictated by nature or because they require intense light that can substantially perturb the very physiology one hopes to study. An exception is structured illumination microscopy (SIM), which can image live cells far faster and with orders of magnitude less light than required for other SR approaches. However, SIM’s resolution is usually limited to only a twofold gain beyond conventional optical microscopes, or ~100 nm with visible light.
RATIONALE
We endeavored to find ways to extend SIM to the sub-100-nm regime while retaining, to the greatest extent possible, the advantages that make it the preferred SR method for live-cell imaging. Our first solution used an ultrahigh numerical aperture (NA) lens and total internal reflection fluorescence (TIRF) to achieve 84-nm resolution at subsecond acquisition speeds over hundreds of time points in multiple colors near the basal plasma membrane. Our second exploited the spatially patterned activation of a recently developed, reversibly photoswitchable fluorescent protein to reach 45- to 62-nm resolution, also at subsecond acquisition, over ∼10 to 40 time points.
RESULTS
We used high-NA TIRF-SIM to image the dynamic associations of cortical filamentous actin with myosin IIA, paxillin, or clathrin, as well as paxillin with vinculin and clathrin with transferrin receptors. Thanks to the combination of high spatial and temporal resolution, we were able to measure the sizes of individual clathrin-coated pits through their initiation, growth, and internalization. We were also able to relate pit size to lifetime, identify and characterize localized hot spots of pit generation, and describe the interaction of actin with clathrin and its role in accelerating endocytosis. With nonlinear SIM by use of patterned activation (PA NL-SIM), we monitored the remodeling of the actin cytoskeleton and the dynamics of caveolae at the cell surface. By combining TIRF-SIM and PA NL-SIM for two-color imaging, we followed the dynamic association of actin with α-actinin in expanding filopodia and membrane ruffles and characterized shape changes in and the transport of early endosomes. Last, by combining PA NL-SIM with lattice light sheet microscopy, we observed, in three dimensions and across the entire volume of whole cells, the dynamics of the actin cytoskeleton, the fusion and fission of mitochondria, and the trafficking of vesicles to and from the Golgi apparatus, each at axial resolution fivefold better than that of conventional widefield microscopy.
In addition, through direct experimental comparisons, we demonstrated that the resolution for our methods is comparable with or better than other SR approaches yet allowed us to image at far higher speeds, and for far longer durations. To understand why this is so, we developed a detailed theoretical model showing that our methods transmit the information encoded in spatial frequencies beyond the diffraction limit with much greater strength than do other alternatives and hence require far fewer photons emitted from the specimen, using far less intense light.
CONCLUSION
High-NA TIRF-SIM and PA NL-SIM fill an unmet need for minimally invasive tools to image live cells in the gap between the 100-nm resolution traditionally associated with SIM and the sub-60-nm regime of protein-specific structural imaging served by single-molecule localization microscopy.
Two approaches for improved live-cell imaging at sub-100-nm resolution.
(
Left
) Association of cortical actin (purple) with clathrin-coated pits (green), the latter seen as rings (
inset
) at 84-nm resolution via a combination of total internal reflection fluorescence and structured illumination microscopy at ultrahigh numerical aperture (high-NA TIRF-SIM). (
Right
) Progression of resolution improvement across the actin cytoskeleton of a COS-7 cell, from conventional, diffraction-limited TIRF (220-nm resolution), to TIRF-SIM (97-nm resolution), and nonlinear SIM based on the patterned activation of a reversibly photoswitchable fluorescent protein (PA NL-SIM, 62 nm resolution). (Left and right represent single frames from time-lapse movies over 91 and 30 frames, respectively. Scale bars, 2 μm (left); 3 μm (right).
Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and α-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions.
Long cycling lifespan is a prerequisite for practical lithium–sulfur batteries yet is restricted by side reactions between soluble polysulfides and the lithium‐metal anode. The regulation on ...solvation structure of polysulfides renders encapsulating polysulfides electrolytes (EPSE) as a promising solution to suppress the parasitic reactions. The solvating power of the solvents in the outer solvent shell of lithium polysulfides is critical for the encapsulation effect of EPSE. Herein, 1,1,2,2‐tetrafluoroethyl‐2,2,3,3‐tetrafluoropropyl ether (HFE) is demonstrated as a superior outer‐shell solvent to construct EPSE. Based on the large steric hindrance of the fluorohydrocarbon chains, the electron‐withdrawing perfluoro segment (CF2 further endows HFE with prominently weak solvating power. The HFE‐EPSE improves the lifespan from 54 to 135 cycles for lithium–sulfur batteries with an ultrathin lithium‐metal anode (50 µm) and high‐areal‐loading sulfur cathode (4.4 mg cm−2). Furthermore, a 334 Wh kg−1 lithium–sulfur pouch cell (2.4 Ah level) with HFE‐EPSE stably undergoes 25 cycles. This work demonstrates the role of weakening solvating power of outer‐shell solvents to construct superior EPSE and inspires the significance of the solvation chemistry of polysulfides to achieve practical lithium–sulfur batteries.
The large steric hindrance of its fluorohydrocarbon chains and the electron‐withdrawing CF2 segments endow 1,1,2,2‐tetrafluoroethyl‐2,2,3,3‐tetrafluoropropyl ether with prominently weak solvating power and high reduction stability. The weakening solvating power of fluorohydrocarbon solvent leads the formation of encapsulating‐lithium polysulfide electrolyte for lithium–sulfur pouch cells with long cycling lifespan.
3D live imaging is important for a better understanding of biological processes, but it is challenging with current techniques such as spinning-disk confocal microscopy. Bessel beam plane ...illumination microscopy allows high-speed 3D live fluorescence imaging of living cellular and multicellular specimens with nearly isotropic spatial resolution, low photobleaching and low photodamage. Unlike conventional fluorescence imaging techniques that usually have a unique operation mode, Bessel plane illumination has several modes that offer different performance with different imaging metrics. To achieve optimal results from this technique, the appropriate operation mode needs to be selected and the experimental setting must be optimized for the specific application and associated sample properties. Here we explain the fundamental working principles of this technique, discuss the pros and cons of each operational mode and show through examples how to optimize experimental parameters. We also describe the procedures needed to construct, align and operate a Bessel beam plane illumination microscope by using our previously reported system as an example, and we list the necessary equipment to build such a microscope. Assuming all components are readily available, it would take a person skilled in optical instrumentation ∼1 month to assemble and operate a microscope according to this protocol.
Enhancer-binding pluripotency regulators (Sox2 and Oct4) play a seminal role in embryonic stem (ES) cell-specific gene regulation. Here, we combine in vivo and in vitro single-molecule imaging, ...transcription factor (TF) mutagenesis, and ChIP-exo mapping to determine how TFs dynamically search for and assemble on their cognate DNA target sites. We find that enhanceosome assembly is hierarchically ordered with kinetically favored Sox2 engaging the target DNA first, followed by assisted binding of Oct4. Sox2/Oct4 follow a trial-and-error sampling mechanism involving 84–97 events of 3D diffusion (3.3–3.7 s) interspersed with brief nonspecific collisions (0.75–0.9 s) before acquiring and dwelling at specific target DNA (12.0–14.6 s). Sox2 employs a 3D diffusion-dominated search mode facilitated by 1D sliding along open DNA to efficiently locate targets. Our findings also reveal fundamental aspects of gene and developmental regulation by fine-tuning TF dynamics and influence of the epigenome on target search parameters.
Display omitted
•Single-cell, single-molecule imaging shows Sox2/Oct4 dynamics in live ES cells•Sox2 locates target via a 3D diffusion-dominated search and 1D sliding along DNA•Sox2/Oct4 enhanceosome forms in a hierarchical binding order•Temporal patterns of target site occupancy are modulated by TF dynamics
A single-cell, single-molecule approach provides a quantitative, real-time view of transcription factors’ search for target sites, revealing a 3D diffusion-dominated search, involving multiple collisions with nonspecific sites, as well as 1D sliding along DNA.
Practical lithium–sulfur (Li−S) batteries are severely plagued by the instability of solid electrolyte interphase (SEI) formed in routine ether electrolytes. Herein, an electrolyte with ...1,3,5‐trioxane (TO) and 1,2‐dimethoxyethane (DME) as co‐solvents is proposed to construct a high‐mechanical‐stability SEI by enriching organic components in Li−S batteries. The high‐mechanical‐stability SEI works compatibly in Li−S batteries. TO with high polymerization capability can preferentially decompose and form organic‐rich SEI, strengthening mechanical stability of SEI, which mitigates crack and regeneration of SEI and reduces the consumption rate of active Li, Li polysulfides, and electrolytes. Meanwhile, DME ensures high specific capacity of S cathodes. Accordingly, the lifespan of Li−S batteries increases from 75 cycles in routine ether electrolyte to 216 cycles in TO‐based electrolyte. Furthermore, a 417 Wh kg−1 Li−S pouch cell undergoes 20 cycles. This work provides an emerging electrolyte design for practical Li−S batteries.
An emerging electrolyte design, which can construct high‐mechanical‐stability solid electrolyte interphase (SEI) on lithium metal anodes, is proposed for practical lithium–sulfur batteries. High‐mechanical‐stability SEI effectively restricts its fracture and ongoing reactions of electrolytes on lithium metal anodes, which notably improves the stability of practical lithium–sulfur coin and pouch cells.
Direct alkylation of the C−H bond arenes in a selective manner is a long‐standing challenge. Herein, a metal‐free photocatalytic regioselective C−H alkylation method for electron‐rich arenes with ...both activated and unactivated alkenes was developed. The reaction tolerates a wide range of aromatic rings with diverse substitution patterns, as well as terminal and internal alkenes, providing a general and straightforward metal‐free method for C−C bond formation from inert C−H bonds. Moreover, alkynes are also compatible to give the C−H vinylation of electron‐rich arenes.
Herein, a metal‐free photocatalyzed site‐ and regioselective C−H alkylation of electron‐rich arenes at room temperature using alkenes as the alkylating reagents is described for the first time. The alkylation proceeds in the absence of any directing groups, and tolerates both activated and unactivated alkenes to deliver alkylated arenes with broad functional‐group tolerance, providing an alternative to the classical Friedel–Crafts alkylation reaction.
The cycle life of high‐energy‐density lithium−sulfur (Li−S) batteries is severely plagued by the incessant parasitic reactions between Li metal anodes and reactive Li polysulfides (LiPSs). ...Encapsulating Li‐polysulfide electrolyte (EPSE) emerges as an effective electrolyte design to mitigate the parasitic reactions kinetically. Nevertheless, the rate performance of Li−S batteries with EPSE is synchronously suppressed. Herein, the sacrifice in rate performance by EPSE is circumvented while mitigating parasitic reactions by employing hexyl methyl ether (HME) as a co‐solvent. The specific capacity of Li−S batteries with HME‐based EPSE is nearly not decreased at 0.1 C compared with conventional ether electrolytes. With an ultrathin Li metal anode (50 μm) and a high‐areal‐loading sulfur cathode (4.4 mgS cm−2), a longer cycle life of 113 cycles was achieved in HME‐based EPSE compared with that of 65 cycles in conventional ether electrolytes at 0.1 C. Furthermore, both high energy density of 387 Wh kg−1 and stable cycle life of 27 cycles were achieved in a Li−S pouch cell (2.7 Ah). This work inspires the feasibility of regulating the solvation structure of LiPSs in EPSE for Li−S batteries with balanced performance.
Hexyl methyl ether (HME) is proposed as a co‐solvent to formulate encapsulating lithium‐polysulfide electrolyte (EPSE). The sacrifice in specific capacity of S cathodes at a high rate in common EPSEs is circumvented in HME‐EPSE while mitigating parasitic reactions of lithium polysulfides with lithium metal anodes. Both high energy density of 387 Wh kg−1 and stable cycle life of 27 cycles were achieved in a lithium−sulfur pouch cell.
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