Ligand Control of Copper-Mediated Cycloadditions of Acetylene to Azides: Chemo- and Regio-Selective Formation of Deutero- and Iodo-Substituted 1,2,3-Triazoles.

The participation of σ-monocopper and σ-bis-copper acetylide in mechanistic pathways for copper-catalyzed cycloaddition (CuAAC) reactions of acetylene with azides was probed by analysis of deuterium distributions in the 1,2,3-triazole product formed by deuterolysis of initially formed mono- and bis-copper triazoles. The results show that, when Cu(Phen)(PPh3)2NO3 is used as the catalyst for reactions of acetylene with azides in DMF/D2O, 1-substituted-5-deutero-1,2,3-triazoles are generated selectively. This finding demonstrates that the Cu(Phen)(PPh3)2NO3-catalyzed cycloadditions utilize monocopper acetylide as the substrate and produce 5-copper-1,2,3-triazoles initially. Conversely, when DBU or Et3N is the copper ligand, the process takes place through initial formation and cycloaddition of bis-copper acetylide to produce 4,5-bis-copper-triazole, which reacts with D2O to form the corresponding 4,5-bis-deutero-triazole. Moreover, when C2D2 is used as the substrate, Cu(Phen)(PPh3)2NO3 as the Cu ligand, and H2O/DMF as the solvent, mono-C4-deutreo 1,2,3-triazoles are generated in high yields and excellent levels of regioselectivity. Lastly, CuAAC reactions of acetylene with azides, promoted by CuCl2·2H2O and NaI, yield 4,5-diiodo-1,2,3-triazoles with moderate to high efficiencies.

Protocol for the synthesis of homoallenic alcohols via allenyl radical-mediated allenylation of alkenes.

Homoallenic alcohols are versatile building blocks to access complex molecules in synthetic chemistry. We present a protocol for accessing homoallenic alcohols by an allenyl radical-involved radical-polar crossover process. We describe steps for preparing solvents and the photoreactor and synthesizing 5-methyl-1-phenyl-3-tosylhexa-3,4-dien-1-ol 3 in 85% yield. In addition, 5-methyl-1-phenyl-3-tosylhexa-3,4-dien-1-ol 3 has been successfully synthesized in 2-mmol scale. This protocol is also applicable to the synthesis of homoallenic amides. For complete details on the use and execution of this protocol, please refer to Wei et al. (2023).1.

Ultrathin C3N4 nanosheets-based oxidase-like 2D fluorescence nanozyme for dual-mode detection of organophosphorus pesticides.

Engineering efficient dual-mode portable sensor with built-in cross reference correction is of great significance for onsite reliable and precise detection of organophosphorus pesticides (OPs) and evading the false-positive outputs, especially in emergency case. Currently, most nanozyme-based sensors for OPs monitoring primarily replied on the peroxidase-like activity, which involved unstable and toxic H2O2. In this scenario, a hybrid oxidase-like 2D fluorescence nanozyme (PtPdNPs@g-C3N4) was yielded by in situ growing PtPdNPs in the ultrathin two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanosheet. When acetylcholinesterase (AChE) hydrolyzed acetylthiocholine (ATCh) to thiocholine (TCh), it ablated O2-• from the dissolved O2 catalyzed by PtPdNPs@g-C3N4's oxidase-like activity, hampering the oxidation of o-phenylenediamine (OPD) into 2,3-diaminophenothiazine (DAP). Consequently, with the increasing concentration of OPs which inhibited the blocking effect by inactivating AChE, the produced DAP caused an apparent color change and a dual-color ratiometric fluorescence change in the response system. Through integrating into a smartphone, a H2O2-free 2D nanozyme-based onsite colorimetric and fluorescence dual-mode visual imaging sensor for OPs was proposed with acceptable results in real samples, which holds vast promise for further development of commercial point-of-care testing platform in early warning and controlling of OPs pollution for safeguarding environmental health and food safety.

Engineering an Enzymatic Cascade Catalytic Smartphone-Based Sensor for Onsite Visual Ratiometric Fluorescence-Colorimetric Dual-Mode Detection of Methyl Mercaptan.

Precise and reliable onsite detection of methyl mercaptan (CH3SH) is of great significance for environmental surveillance. Here, we synthesized a novel blue fluorescence nanozyme CeO2@TPE with high peroxidase-like activity by employing aggregation-induced emission (AIE) tetraphenylethene (TPE) to embed into hollow CeO2 nanospheres. In the presence of ethanol oxidase (AOX) and o-phenylenediamine (OPD), we engineered an enzymatic cascade activation ratiometric fluorescence-colorimetric dual-mode system AOX/CeO2@TPE + OPD toward CH3SH. In this design, CH3SH initiated AOX catalytic activity to convert it into H2O2 for activating the peroxidase-like activity of CeO2@TPE, producing •OH for oxidizing the naked-eye colorless OPD into deep yellow 2,3-diaminophenazine (DAP) with an absorption enhancement at ∼425 nm, companied by a new emission peak at ∼550 nm to match with the intrinsic emission at ∼441 nm for observing ratiometric fluorescence response, enabling a ratiometric fluorescence-colorimetric dual-mode analysis. Interestingly, both the ratiometric fluorescence and colorimetric signals could be gathered for being converted into the hue parameter on a smartphone-based sensor, achieving the onsite visual fluorescence-colorimetric dual-mode detection of CH3SH in real environmental media with acceptable results. This study gave a novel insight into designing target-responsive enzymatic cascade activation system-based efficient and reliable dual-mode point-of-care sensors for safeguarding environmental health.

High-Efficiency Utilization of Waste Tobacco Stems to Synthesize Novel Biomass-Based Carbon Dots for Precise Detection of Tetracycline Antibiotic Residues.

Recycling waste biomass into valuable products (e.g., nanomaterials) is of considerable theoretical and practical significance to achieve future sustainable development. Here, we propose a one-pot hydrothermal synthesis route to convert waste tobacco stems into biomass-based N, S-codoped carbon dots (C-dots) with the assistance of carbon black. Unlike most of the previously reported luminescent C-dots, these biomass-based C-dots showed a satisfactory stability, as well as an excitation-independent fluorescence emission at ~520 nm. Furthermore, they demonstrated a pH-dependent fluorescence emission ability, offering a scaffold to design pH-responsive assays. Moreover, these as-synthesized biomass-based C-dots exhibited a fluorescence response ability toward tetracycline antibiotics (TCs, e.g., TC, CTC, and OTC) through the inner filter effect (IFE), thereby allowing for the establishment a smart analytical platform to sensitively and selectively monitor residual TCs in real environmental water samples. In this study, we explored the conversion of waste tobacco stems into sustainable biomass-based C-dots to develop simple, efficient, label-free, reliable, low-cost, and eco-friendly analytical platforms for environmental pollution traceability analysis, which might provide a novel insight to resolve the ecological and environmental issues derived from waste tobacco stems.

Engineering of 2D artificial nanozyme-based blocking effect-triggered colorimetric sensor for onsite visual assay of residual tetracycline in milk.

Accurate and low-cost onsite assay of residual antibiotics in food and agriculture-related matrixes (e.g., milk) is of significant importance for evaluating and controlling food pollution risk. Herein, we employed hybrid Cu-doped-g-C3N4 nanozyme to engineer smartphone-assisted onsite visual sensor for reliable and precise reporting the levels of tetracycline (TC) residues in milk through π-π stacking-triggered blocking effect. Benefiting from the synergetic effects of Cu2+ and g-C3N4 nanosheet, Cu-doped-g-C3N4 nanocomposite exhibited an improved peroxidase-like activity, which could effectively catalyze H2O2 to oxidate colorless TMB into steel-blue product oxTMB. Interestingly, owing to the blocking effect caused by the π-π stacking interaction between TC tetraphenyl skeleton and Cu-doped-g-C3N4 nanozyme, the affinity of Cu-doped-g-C3N4 nanocomposite toward the catalytic substrates was remarkably blocked, resulting in a TC concentration-dependent fading of solution color. Using smartphone-assisted detection a simple, low-cost, reliable, and sensitive portable colorimetric sensor-based nanozyme for onsite visual monitoring the residual TC in milk was successfully developed with a detection limit of 86.27 nM. Of particular mention is that this detection limit is comparable to most other reported colorimetric methods and below most official allowable residue thresholds in milk matrixes. This work gave a novel insight to integrate two-dimensional (2D) artificial nanozymes-based π-π stacking-triggered blocking effect with smartphone-assisted detection for developing efficient and low-cost colorimetric point-of-care testing of the risk factors in food and agriculture-related matrixes.

Engineering of Portable Smartphone Integrated with Liposome-Encapsulated Curcumin for Onsite Visual Ratiometric Fluorescence Imaging of Hypochlorite.

Precisely onsite monitoring of hypochlorite (ClO- ) is of great significance to guide its rational use, reducing/avoiding its potential threat toward food safety and human health. Considering ClO- could quench fluorescence of curcumin (CCM) by oxidizing the o-methoxyphenol of CCM into benzoquinone, a portable ratiometric fluorescence sensor integrated with smartphone was designed for realizing the visual point-of-care testing (POCT) of ClO- . The amphiphilic phospholipid polymer was used as carrier to wrap curcumin, forming a novel liposome-encapsulated CCM, which provided a scaffold to bind with [Ru(bpy)3 ]2+ through electrostatic interaction, thus assembling [Ru(bpy)3 ]2+ -functionalized liposome-encapsulated CCM ([Ru(bpy)3 ]2+ @CCM-NPs). Further integrated with smartphone, visual imaging of [Ru(bpy)3 ]2+ @CCM-NPs could be achieved and the accurate onsite detection of ClO- could be realized with a detection limit of 66.31 nM and a linear range of 0.2210 to 80.0 µM. In addition, the sensor could monitor ClO- in real samples with an onsite detection time of ∼154.0 s.

Engineering of an Upconversion Luminescence Sensing Platform Based on the Competition Effect for Mercury-Ion Monitoring in Green Tea.

Accurately monitoring mercury ions (Hg2+) in food and agriculture-related matrixes (e.g., green tea) is of great significance to safeguard food safety. Here, we employed upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) to engineer a cysteine (Cys)-assisted anti-Stokes luminescence sensing platform (UCNPs-AuNPs) for precisely detecting residual Hg2+ in green tea through the competition effect. Initially, AuNPs could effectively quench the luminescence of UCNPs through the luminescence resonance energy transfer process, which was then interrupted by Cys-triggered AuNP aggregation via Au-S, thereby restoring UCNP luminescence. Interestingly, owing to the competition effect with AuNPs toward Cys, Hg2+ could weaken the luminescence restoring efficiency, achieving a Hg2+ concentration-dependent luminescence change. On this basis, a facile, reliable, and sensitive upconversion luminescence sensing platform for monitoring residual Hg2+ in green tea was successfully established. This study offers a novel insight into integrating the competition effect and anti-Stokes luminescence for food- and agriculture-related contaminant monitoring.

Alkene Difunctionalization Triggered by a Stabilized Allenyl Radical: Concomitant Installation of Two Unsaturated C-C Bonds.

Radical-mediated difunctionalization of alkenes provides a promising approach to introduce one alkenyl or alkynyl group to target compounds. However, simultaneous installation of two unsaturated C-C bonds via alkene difunctionalization remains elusive, attributable to the high instability and transient lifetimes of alkenyl and alkynyl radicals. Herein, we report the photocatalytic 1,2-alkynylalkenylation and 1,2-enynylalkenylation of alkenes for the first time, triggered by the intermolecular addition of a stabilized allenyl radical to an alkene. A portfolio of strategically designed, easily accessible dual-function reagents are applied to a radical docking-migration cascade. The protocol has broad substrate scope and efficiently increases the degree of unsaturation.

Evaluating the potential risk by probing the site-selective binding of rutin-Pr(III) complex to human serum albumin.

Having reported that rare earth elements displayed potential toxicity in vivo, often be found in soil, plants and etc., which might be easily chelated with the natural functional molecule rutin to form rutin metal complexes, ultimately entering the human body by means of food chain. However, few reports paid the attention on the toxicology of the complexes consisting of rutin with rare earth ions. Here, we focused on the potential toxicity by probing the site-selective binding of the rutin-rare earth ions complexes to human serum albumin (HSA). As a proof-of-concept, we selected Pr3+ as the representative to conjugate with rutin to form rutin-Pr(III) complex, which was further applied to interact with HSA in aqueous solution. The results exhibited that the rutin-Pr(III) complex primary bound to the hydrophobic cavity at site II (subdomain IIIA) of HSA through hydrogen bonding and van der Waals force. Through the thermomechanical analysis, we found this binding process was spontaneous because of the negative ΔG. We believe that this work may offer a new insight into understanding the physiological effects (e.g. toxicology) of rutin and rare earth ions, which could be helpful to guide their rational use in the agriculture and environment-related industries.

Enantiospecific Generation and Trapping Reactions of Aryne Atropisomers.

Enantioenriched aryne atropisomers having a biaryl stereogenic axis vicinal to the reactive triple bond are demonstrated to exist. These reaction intermediates are easily produced in situ and can undergo the standard aryne cycloaddition chemistry in an enantiospecific manner. Notably, the aryne atropisomers herein have allowed the practical syntheses of a small nanographene as well as some triptycene and anthracene derivatives that embed stereogenic axes of controlled absolute configurations.

Radical-Mediated Heck-Type Alkylation: Stereoconvergent Synthesis of Functionalized Polyenes.

The stereospecific synthesis of polyenes is of great synthetic value. Disclosed herein is a new, efficient, stereoconvergent approach for the synthesis of functionalized polyenes via a radical-mediated Heck-type alkylation. The easily accessed Z- and E-mixed alkenes are harnessed as starting material, leading to a unique stereoisomer of polyenes. In addition, the transformation features mild reaction conditions and broad functional group compatibility. A variety of valuable 1,3-dienes and 1,3,5-trienes are afforded in useful yields.

Synthesis of indolo[2,1-a]isoquinoline derivatives via visible-light-induced radical cascade cyclization reactions.

We describe a photocatalyzed transformation for the synthesis of the indolo[2,1-a]isoquinoline core structure. This redox neutral reaction features mild reaction conditions and exceptional functional group tolerance. A series of valuable indolo[2,1-a]isoquinoline derivatives bearing various functional groups were synthesized using this method in good to excellent yields.

Enantioselective Organocatalytic Four-Atom Ring Expansion of Cyclobutanones: Synthesis of Benzazocinones.

An enantioselective Michael addition- four-atom ring expansion cascade reaction involving cyclobutanones activated by a N-aryl secondary amide group and ortho-amino nitrostyrenes has been developed for the preparation of functionalized eight-membered benzolactams using bifunctional aminocatalysts. Taking advantage of the secondary amide activating group, the eight-membered cyclic products could be further rearranged into their six-membered isomers having a glutarimide core under base catalysis conditions without erosion of optical purity, featuring an overall ring expansion- ring contraction strategy.

Unusual ent-atisane type diterpenoids with 2-oxopropyl skeleton from the roots of Euphorbia ebracteolata and their antiviral activity against human rhinovirus 3 and enterovirus 71.

Two novel ent-atisane type diterpenoids possessing the extra unusal 2-oxopropyl moiety (1 and 2) and four known analogues have been isolated from the roots of Euphorbia ebracteolata. The structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography, 13C NMR calculation, and electronic circular dichroism spectra calculation. Compounds 1 and 2 are the first examples of natural products with ent-atisane type diterpenoids possessing 2-oxopropyl skeleton. Compounds 2, 3, 5, and 6 show antiviral activities against human rhinovirus 3, with IC50 values of 25.27-90.35 µM. Compounds 5 and 6 showed moderate antiviral activities against EV71 at a concentration of 100 µM.

Diterpenoids from the roots of Euphorbia ebracteolata and their anti-tuberculosis effects.

Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis. The present work has performed the investigation of bioactive chemical substances from the roots of E. ebracteolata. Using various chromatographic techniques, 15 compounds were obtained from the roots of E. ebracteolata. On the basis of widely spectroscopic data analyses, the isolated compounds were determined to be diterpenoids, including rosane derivatives (1-12), isopimarane (13), abietane (14), and lathyrane (15), among which compounds 1-4, and 9 were undescribed previously. The inhibitory effects of isolated diterpenoids against Mycobacterium tuberculosis were evaluated using an Alamar blue cell viability assay. And two rosane-type diterpenoids 3 and 8 displayed moderate inhibitory effects on with the MIC values of 18 µg/mL and 25 µg/mL, respectively. For the potential inhibitor 3, the inhibitory effect against the target enzyme GlmU was evaluated, which displayed a moderate inhibitory effect with the IC50 12.5 µg/mL. Therefore, the diterpenoids from the roots of E. ebracteolata displayed anti-tuberculosis effects, which would be pay more attentions for the anti-tuberculosis agents.

Alkene functionalization for the stereospecific synthesis of substituted aziridines by visible-light photoredox catalysis.

A novel strategy involving visible-light-induced functionalization of alkenes for the synthesis of substituted aziridines was developed. The readily prepared N-protected 1-aminopyridinium salts were used for the generation of N-centered radicals. This approach allowed the synthesis of aziridines bearing various functional groups with excellent diastereoselectivity under mild conditions. Moreover, this protocol was successfully applied to prepare structurally diverse nitrogen-containing frameworks.

Chemical characteristics of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesterase.

The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 µM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE.

Diterpenoids from the roots of Euphorbia fischeriana and their inhibitory effects on α-glucosidase.

Chemical investigation has been performed on the roots of Euphorbia fischeriana, a traditional Chinese medicine. Three diterpenoids were obtained using various chromatographic techniques, and their structures were determined by spectroscopic data including HRESIMS, 1D NMR, 2D NMR, ECD, and calculated ECD, which gave two new diterpenoids, daphnane type (1) and ent-pimarene type (3). Additionally, the isolated compounds (1-3) displayed moderate inhibitory effects against α-glucosidase in an in vitro bioassay.

Direct Decarboxylative-Decarbonylative Alkylation of α-Oxo Acids with Electrophilic Olefins via Visible-Light Photoredox Catalysis.

The decarbonylation of primary, secondary, and tertiary alkyl-substituted acyl radicals has been investigated through photoredox catalysis. A series of quaternary carbons and γ-ketoesters have been directly constructed by the photoredox 1,4-conjugate addition of the corresponding alkyl ketoacids with electrophilic alkenes. And, the tertiary alkyl ketoacids have proved to be good precursors of tertiary alkyl radicals.