Rapid Click Research Articles

Algae-based self-driven microrobot for efficient removal of nanoplastics from water environment

Nanoplastics (NPs) have the characteristics of various species, wide distribution, low concentration and difficult degradation. In recent years, the researches of NPs have mainly focused on its toxicity, origin and migration, and the quantitative detection and removal technology of NPs is an urgent technical problem to be solved. Here, an active biohybrid microrobots (DPA-algae robots, diphenolic acids-alage robots) was designed and developed for dynamic removal of NPs in water environment. Firstly, diphenolic acids were functionalized on algae to realize the specific adsorption of nanoplastics through hydrophobic force, electrostatic attraction and van der Waals force between diphenolic acids and nanoplastic particles. Secondly, to realize the rapid identification of NPs, the functionalized algae were assembled into microrobots through rapid click chemistry reaction, thus the self-propulsion ability of algae can be utilized to accelerate the identification and enrichment of target objects. The removal rate of nanoplastics by microalgae robots has increased to 83.1 % at the concentration of 0.125 mg/mL within 2 h compared with the unmodified algae, which is a very significant improvement. In addition, the removal rate was 84.1 % to 87.7 % in different media, so the dynamic removal of NPs is expected to be applied into the filtration process of waterworks by preparing a large number of algae-based microrobots. This multi-functional microrobot is cost-effective and biocompatible, providing a new solution to the global “plastic crisis”.

A Bioorthogonal Antidote Against the Photosensitivity after Photodynamic Therapy.

As an effective and non-invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber-optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post-PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black-hole quencher BHQ-3 conjugated with a bicyclo[6.1.0]non-4-yne (BCN) moiety and a tetrazine-substituted boron dipyrromethene-based photosensitizer. By using tumor-bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ-3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT.

Chemical Tailoring of Aptamer Glues with Significantly Enhanced Recognition Ability for Targeted Membrane Protein Degradation.

Cell membrane proteins play a crucial role in the development of early cancer diagnosis strategies and precision medicine techniques. However, the application of aptamers in cell membrane protein-based biomedical research is limited by their inherent drawbacks, such as sensitivity to the recognition environment and susceptibility to enzymatic degradation, which leads to the loss of recognition ability. To address these challenges, this study presents a subzero-temperature-enabled molecule stacking strategy for the on-demand tailoring of aptamer glues for the precision recognition and efficient degradation of membrane protein. Mechanistic studies revealed that nucleic acid molecule stacking occurred during the freezing and melting processes, facilitating a rapid click reaction by bringing two reactive groups together. In vitro investigations demonstrated that the strategy confers aptamer glues with significantly enhanced specific recognition ability and binding affinity, allowing the distinction of a targeted cell line from a nontargeted cell line. Moreover, the engineered aptamer glue exhibited impressive targeted cell membrane protein degradation ability; around 74% of the c-Met protein was degraded in 24 h. These findings hold great potential for advancing cancer diagnosis and targeted therapy through the development of more stable and reliable aptamer probes.

Sleep-like changes in neural processing emerge during sleep deprivation in early auditory cortex.

Insufficient sleep is commonplace in modern lifestyle and can lead to grave outcomes, yet the changes in neuronal activity accumulating over hours of extended wakefulness remain poorly understood. Specifically, which aspects of cortical processing are affected by sleep deprivation (SD), and whether they also affect early sensory regions, remain unclear. Here, we recorded spiking activity in the rat auditory cortex along with polysomnography while presenting sounds during SD followed by recovery sleep. We found that frequency tuning, onset responses, and spontaneous firing rates were largely unaffected by SD. By contrast, SD decreased entrainment to rapid (≥20Hz) click trains, increased population synchrony, and increased the prevalence of sleep-like stimulus-induced silent periods, even when ongoing activity was similar. Recovery NREM sleep was associated with similar effects as SD with even greater magnitude, while auditory processing during REM sleep was similar to vigilant wakefulness. Our results show that processes akin to those in NREM sleep invade the activity of cortical circuits during SD, even in the early sensory cortex.

High Rates of Quinone-Alkyne Cycloaddition Reactions are Dictated by Entropic Factors.

Reaction rates of strained cycloalkynes and cycloalkenes with 1,2-quinone were quantified by stopped flow UV-Vis spectroscopy and computational analysis. We found that the strained alkyne BCN-OH 3 (k2 1824 M-1s-1) reacts >150 times faster than the strained alkene TCO-OH 5 (k2 11.56 M-1s-1). Also, the 8-membered strained alkyne BCN-OH 3 reacts 16 times faster than the more strained 7-membered THS 2 (k2 110.6 M-1s-1). Using the linearized Eyring equation we determined the thermodynamic activation parameters of these two strained alkynes, revealing that the SPOCQ reaction of quinone 1 with THS 2 is associated with ΔH‡ of 0.80 kcal/mol, ΔS‡ = -46.8 cal/K·mol, and ΔG‡ = 14.8 kcal/mol (at 25 °C), whereas the same reaction with BCN-OH 3 is associated with, ΔH‡ = 2.25 kcal/mol, ΔS‡ = -36.3 cal/K·mol, and ΔG‡ = 13.1 kcal/mol (at 25 °C). Computational analysis supported the values obtained by the stopped-flow measurements, with calculated ΔG‡ of 15.6 kcal/mol (in H2O) for the SPOCQ reaction with THS 2, and with ΔG‡ of 14.7 kcal/mol (in H2O) for the SPOCQ reaction with BCN-OH 3. With these empirically determined thermodynamic parameters, we set an important step towards a more fundamental understanding of this set of rapid biogenic click reactions.

Engineering of M2 Macrophages-Derived Exosomes via Click Chemistry for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is one of the most common causes of death and disability. The effective modulation of complicated microenvironment, regeneration of injured spinal cord tissue, and the functional recovery after SCI are still clinical challenges. Recently, macrophages-derived exosomes have shown great potential for various diseases due to their inflammation-targeting property. However, further modifications are needed to endow exosomes with the neural regenerative potential for SCI recovery. In the current study, a novel nanoagent (MEXI) is designed for SCI treatment by conjugating bioactive IKVAV peptides to the surface of M2macrophages-derived exosomes via an easy and rapid click chemistry method. In vitro, MEXI inhibits the inflammation by reprograming macrophages and promotes neuronal differentiation of neural stem cells. In vivo, engineered exosomes target the injured site of the spinal cord after tail vein injection. Furthermore, histological analysis reveals that MEXI improves motor functional recovery of SCI mice by reducing infiltration of macrophages, downregulating pro-inflammatory factors, and improving the regeneration of injured nervous tissues. Taken together, this study provides strong evidence for the significance of MEXI in SCI recovery.

In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.

Relative changes in the cochlear summating potentials to paired-clicks predict speech-in-noise perception and subjective hearing acuity.

Objective assays of human cochlear synaptopathy (CS) have been challenging to develop. It is suspected that relative summating potential (SP) changes are different in listeners with CS. In this proof-of-concept study, young, normal-hearing adults were recruited and assigned to a low/high-risk group for having CS based on their extended audiograms (9-16 kHz). SPs to paired-clicks with varying inter-click intervals isolated non-refractory receptor components of cochlear activity. Abrupt increases in SPs to paired- vs single-clicks were observed in high-risk listeners. Critically, exaggerated SPs predicted speech-in-noise and subjective hearing abilities, suggesting relative SP changes to rapid clicks might help identify putative synaptopathic listeners.

Spatiotemporal trends in bottlenose dolphin foraging behavior and relationship to environmental variables in a highly urbanized estuary

Marine predator foraging influences community structure and ecosystem functions, which are all linked with environmental variables. Determining variables that are associated with foraging can facilitate the identification of important habitats, which is particularly important in heavily urbanized systems. In the New York-New Jersey Harbor Estuary, bottlenose dolphinsTursiops truncatusare exposed to various stressors, including vessel activity and forthcoming offshore wind development. Here, we used passive acoustic monitoring to identify foraging conditions for dolphins from April-October of 2018-2020. When foraging, dolphins produce a series of rapid clicks (‘foraging buzzes’) which can be used as a proxy for foraging activity. We analyzed the relationship between acoustic detections of dolphins and environmental variables using a generalized additive modeling framework. The variables week, sea surface temperature (SST), and chlorophylla(chla) concentration were significantly associated with foraging activity at seasonal timescales. Foraging increased with increasing SST and water levels, with the peak of foraging occurring in autumn. The relationship between chlaconcentration and foraging was not straightforward and warrants further research. Diel foraging trends varied seasonally and annually. These results suggest that passive acoustic monitoring and environmental variables may be used to investigate marine mammal behavior and assess seasonal foraging habitat for marine predators within dynamic, heterogenous, and human-dominated environments. Baseline data on dolphin habitat use is vital given the continued expansion of anthropogenic activities and climate-driven shifts in oceanographic conditions that are occurring in this region.

A Facile, Efficient Step-Wise and Alternative Synthesis of Indolyl Triazoles via “Click” Chemistry

series of new 1,2,3 triazoles hybrids were synthesized using a Cu-catalysed azide-alkyne cycloaddition reaction. Thus, a remarkable rapid click reaction of aryl azides with terminal alkynes at room temperature in DMF afforded new 4-((1-((1-(4-methoxy-3-nitrophenyl)-1H-1,2,3-triazol-4- yl)methyl)-1H-indol-3-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-ones in good to excellent yields. The reaction provides a safe, efficient and economic approach for the synthesis of various 1,2,3 triazoles. The reaction has many advantages like shorter reaction times, good yields of products and isolation of the products without the need for column chromatography. By using knoevenagel reaction under physical grinding with alkylating agents prepared various 1,2,3 triazoles.

Behavioral context of echolocation and prey-handling sounds produced by killer whales (Orcinus orca) during pursuit and capture of Pacific salmon (Oncorhynchus spp.).

Availability of preferred salmonid prey and a sufficiently quiet acoustic environment in which to forage are critical to the survival of resident killer whales (Orcinus orca) in the northeastern Pacific. Although piscivorous killer whales rely on echolocation to locate and track prey, the relationship between echolocation, movement, and prey capture during foraging by wild individuals is poorly understood. We used acoustic biologging tags to relate echolocation behavior to prey pursuit and capture during successful feeding dives by fish‐eating killer whales in coastal British Columbia, Canada. The significantly higher incidence and rate of echolocation prior to fish captures compared to afterward confirms its importance in prey detection and tracking. Extremely rapid click sequences (buzzes) were produced before or concurrent with captures of salmon at depths typically exceeding 50 m, and were likely used by killer whales for close‐range prey targeting, as in other odontocetes. Distinctive crunching and tearing sounds indicative of prey‐handling behavior occurred at relatively shallow depths following fish captures, matching concurrent observations that whales surfaced with fish prior to consumption and often shared prey. Buzzes and prey‐handling sounds are potentially useful acoustic signals for estimating foraging efficiency and determining if resident killer whales are meeting their energetic requirements.

Multifunctional Clickable Reagents for Rapid Bioorthogonal Astatination and Radio-Crosslinking.

Invited for this month's cover is the group of Dr. Hannes Mikula at Vienna University of Technology (TU Wien), Austria. The cover picture shows immobilized astatine-labeled reagents that have been sterically shielded with polyethylene chains by rapid bioorthogonal ligation leading to increased stability of the radiolabel in biological media. These multifunctional and bioorthogonal 211 At reagents can be efficiently prepared by rapid click assembly and simultaneous astatination. Read the full text of the article at 10.1002/cplu.201900114.

Catalyst-free cycloaddition of 1,3-diene-1-carbamates with azodicarboxylates: A rapid click reaction.

Novel click reactions are of continued interest in many scientific research areas and applications. Herein, we report a novel practical, catalyst-free, azo-Diels-Alder reaction between dienecarbamates and azodicarboxylates exhibiting a remarkable functional group tolerance. The availability of starting materials, mild reaction conditions, chemoselectivity and scalability make this cycloaddition a viable supplement to the other reactions in "click" chemistry.

One‐Pot Preparation of Macroporous Organic‐Silica Monolith for the Organics‐/Oil‐Water Separation

AbstractThree‐dimensional porous monoliths have been considered as attractive candidates for the organics‐/oil‐water separation due to their high porosity, low density and hydrophobic/oleophilic property. To simplify the preparation process, one‐pot method based on thiol‐methacrylate click polymerization was developed to fabricate macroporous organic‐silica monolith by using octakis(3‐mercaptopropyl)octasilsesquioxane, ethylene glycol dimethacrylate and heptadecafluorodecyl methacrylate as starting monomers. The rapid click polymerization was carried out at room temperature under air atmosphere, which made it possible for preparation of monolith with desired scale and geometry. The hybrid monolith with good thermal stability and compressibility generated through‐pores with diameter ranging from several microns to tens of microns. As a result of the flexible organic linkages and fluorocarbon groups, the hybrid monolith showed hydrophobic feature, and could be fast swollen in organic liquids. Particularly, a cylindrical hybrid monolith (15 mm in diameter × 11 mm in height) supported by a modified syringe, which exhibited excellent recyclability and swelling‐squeezing performance, has been applied to selectively absorb organic liquids located on the upper or under water layer.

Click chemistry reaches a new dimension

In 2014, K. Barry Sharpless and coworkers at Scripps Research Institute California developed sulfur fluoride exchange (SuFEx), a simple and rapid click chemistry reaction that uses sulfuryl fluoride (SO2F2) to make carbon-sulfate links. They used the technique to synthesize disulfates, polysulfate polymers, and other linear products. Suhua Li, Sharpless, and coworkers have now devised a variation that kicks SuFEx click chemistry into another dimension. Using thionyl tetrafluoride (SOF4) instead of SO2F2 as a SuFEx reagent enables them to make up to three tetrahedrally oriented connections to each sulfur hub molecule instead of two linear linkages (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201611048). Thionyl tetrafluoride reacts initially with a primary amino group, forming a tetrahedral iminosulfur product with two fluoride “handles.” One fluoride or both can then react with aryl alcohols or alkyl amines to create products that are doubly or triply substituted along the sulfur hub’s tetrahedral axes. Potential applications

An injectable and fast-degradable poly(ethylene glycol) hydrogel fabricated via bioorthogonal strain-promoted azide-alkyne cycloaddition click chemistry.

Biocompatible and degradable injectable materials prepared via bioorthogonal reactions are highly promising for biomedical applications because they can be formed in situ and administered in a minimally invasive way. In this work, a PEG-based injectable hydrogel was fabricated via a copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Azide and cyclooctyne moieties on the PEG backbones underwent a rapid click reaction to trigger the formation of the hydrogel within several minutes. Resulting from the introduction of ester groups into the cross-linked network, the hydrogel presented pH-dependent hydrolysis and biological fast degradability. Good biocompatibility of the hydrogel was verified by in vitro cytotoxicity assay and in vivo studies. The hydrogel formed in situ after subcutaneously injecting the gel precursors into Kungming (KM) mice. The implanted hydrogel caused a mild inflammatory response in vivo, and the surrounding tissues fully recovered a week after the injection. The injectable and fast-degradable hydrogel fabricated by the bioorthogonal click reaction may be useful as biomaterials such as embolic agents for interventional therapy.

The nitrilimine–alkene cycloaddition is an ultra rapid click reaction

The transient formation of nitrilimine in aqueous conditions is greatly influenced by pH and chloride. In basic conditions (pH 10) with no chloride, a diarylnitrilimine precursor readily ionizes to form diarylnitrilimine that reacts almost instantly with an acrylamide-containing protein and fluorescently labels it.

Modified Brain Stem Auditory Evoked Potentials in Patients With Intracranial Mass Lesions

The authors report their experience utilizing a recently described rapid rate, binaural click and 1000-Hz tone burst modification of the brain stem auditory evoked potentials (BAEP), modified (MBP), in 27 symptomatic patients with non-brain stem compressive space-taking cerebral lesions (22), hydrocephalus (4), and pseudotumor cerebri (1). Many presented with clinical signs suggestive of increased intracranial pressure (ICP) and focal neurological deficits. The cerebral lesions, mostly large tumors with edema, had very substantial radiological signs of mass effect. Fourteen patients were also studied following surgical decompression. A number of significant changes in the wave V and Vn latency/intensity and less so amplitude/intensity function was found in the 27 patients, compared to normal volunteers, as well as those studied pre- and postoperatively. Similar MBP changes had been noted in normal volunteers placed in a dependent head position. Possible mechanisms to explain these findings are discussed. The MBP methodology shows promise and further development could make neuro-intensive care unit monitoring practical.

A rapid synthesis of lavendustin-mimetic small molecules by click fragment assembly

Lavendustin-mimetic small molecules modifying the linker –CH 2–NH– with an 1,2,3-triazole ring have been synthesized via a click chemistry. Two pharmacophoric fragments of lavendustin were varied to investigate chemical space and the auxophoric –CH 2–NH– was altered to an 1,2,3-triazole for rapid click conjugation. The small molecules were evaluated against HCT116 colon cancer and CCRF-CEM leukemia cell lines. Among 28 analogues, 3-phenylpropyl ester 26b inhibited CCRF-CEM leukemia cell growth with GI 50 value of 0.9 μM.

How toothed whales echolocate to find and capture prey in the deep ocean

Sperm and beaked whales dive to feed on squid and deepwater fish. We have attached sound‐and‐orientation recording tags to study how these whales use echolocation to forage at depth. Tagged whales are usually silent when starting a dive, but start producing echolocation clicks at a few hundred meters depth, shallower than the depth at which they feed, suggesting that descending whales scan the deep layers where they will feed. Once sperm or beaked whales encounter prey, they switch from regular search clicks to a buzz of rapid clicks. Tags on beaked whales not only record outgoing clicks, but also echoes from prey at ranges out to 10‐20 m. Beaked whales produce clicks every 0.2‐0.4 sec when searching. Echoes from several targets are often detected after each beaked whale click. Beaked whales will pass by many targets before selecting one. Whales may switch from the search clicks to a buzz as they close within a body length of the prey. Sperm and beaked whales have an angular acceleration at the end of the buzz, which probably indicates turning to catch the prey.