Electrochemical Trifluoromethylation and Sulfonylation of N-Allylamides: Synthesis of Oxazoline Derivatives.

We report a new method for the synthesis of trifluoromethylated and sulfonylated oxazolines by electrochemical radical cascade cyclizations of N-allylamides with sodium trifluoromethanesulfinate or sulfonylhydrazines. This protocol provides a green and useful strategy to synthesize trifluoromethylated and sulfonylated oxazolines with a broad substrate scope under ambient conditions.

Annulation Reaction of Quinoxalin-2(1H)-ones Initiated by Electrochemical Decarboxylation of N-Arylglycines.

A new methodology for the synthesis of tetrahydroimidazo[1,5-a]quinoxalin-4(5H)-ones has been accomplished through annulation of quinoxalin-2(1H)-ones initiated by electrochemical decarboxylation of N-arylglycines catalyzed by ferrocene. With a pair of oxidative and reductive processes occurring among the substrates and intermediates instead of on the electrodes, the electricity consumption was decreased.

Hydropyridylation of α,ß-Unsaturated Esters through Electroreduction of 4-Cyanopyridine.

A mild and highly efficient method for the hydropyridylation of α,ß-unsaturated esters has been developed. This protocol provides the products smoothly with a wide substrate scope in an undivided cell under ambient conditions. Moreover, studies showed that the scope could be extended to other unsaturated compounds, including enones and aldehydes.

Monitoring and mechanisms of insecticide resistance in Spodoptera exigua (Lepidoptera: Noctuidae), with special reference to diamides.

The beet armyworm, Spodoptera exigua, is a major lepidopteran pest of global importance in cultivation of numerous crops including cotton, maize, soybean, onion, cabbage, and ornamentals. It has evolved resistance to different insecticides. However, the current status of insecticide resistance in S. exigua has not been well examined in China. In this study, concentration-mortality responses of S. exigua to seven insecticides, including chlorantraniliprole, tetraniliprole, methoxyfenozide, indoxacarb, chlorfenapyr, emamectin benzoate and beta-cypermethrin were evaluated. The results showed that most of the tested populations had developed moderate to high resistance to chlorantraniliprole, with resistance ratios ranging from 6.3 to 2477.3-fold. Our results also showed that chlorantraniliprole have cross-resistance with tetraniliprole in S. exigua. The AY19 population collected from Anyang in Henan Province in 2019 exhibited a high resistance level to beta-cypermethrin (RR = 277.5). Methoxyfenozide and chlorfenapyr were highly effective against all of the tested populations with resistance ratios (RR) ranging from 0.1 to 2.2-fold. One of the tested populations showed moderate resistance to indoxacarb and emamectin benzoate. We detected the known ryanodine receptor target site resistance mutation, I4743M, in the field populations of S. exigua with different levels of diamide resistance.

Susceptibility of fall armyworm, Spodoptera frugiperda (J.E.Smmith), to eight insecticides in China, with special reference to lambda-cyhalothrin.

Fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is the main destructive insect pest of grain crops that occurs in all maize growing regions of the Americas. It has rapidly invaded the Southern China since January 2019. However, the current status of insecticide resistance in S. frugiperda has not been reported in China. In this study, we determined the susceptibility of eight populations of FAW to eight insecticides by an artificial diet incorporation method. The results showed that among eight insecticides, emamectin benzoate, spinetoram, chlorantraniliprole, chlorfenapyr, and lufenuron showed higher toxicity to this pest, while lambda-cyhalothrin and azadirachtin exhibited lower toxicity. Susceptibility of S. frugiperda to indoxacarb was significantly different (10.0-fold for LC50) across the various geographic populations. To investigate the biochemical mechanism of FAW to lambda-cyhalothrin, we performed the synergism tests and the results showed that piperonyl butoxide (PBO) and triphenyl phosphate (TPP) produced a high synergism of lambda-cyhalothrin effects in the two field populations. Sequencing of the gene encoding the acetylcholinesterase (AChE) gene in the two field populations identified two amino acid mutations, all of which have been shown previously to confer resistance to organophosphates (OPs) in several arthropod species. The results of this study provided valuable information for choosing alternative insecticides and for insecticide resistance management of S. frugiperda.

Superoxide dismutase from venom of the ectoparasitoid Scleroderma guani inhibits melanization of hemolymph.

Superoxide dismutase (SOD) known as an important antioxidative stress protein has been recently found in venoms of several parasitoid wasps. However, its functions and characteristics as a virulent factor remain scarcely described. Here, we report the characterization of two venomous SOD genes (SguaSOD1 and SguaSOD3) from the ectoparasitoid, Scleroderma guani. The metal binding sites, cysteine amino acid positions and signature sequences of the SOD family were conserved within SguaSOD1 and SguaSOD3. Relatively high levels of their transcripts were observed in pupae followed a decrease in early adults, after which they had the highest transcriptions, indicating that their productions would be regulated in venom apparatus. Although the two genes showed lower expression in venom apparatus compared to head and thorax, the enzymatic assay revealed that SOD indeed had activity in venom. Further, we showed that recombinant SguaSOD3 suppressed melanization of host hemolymph, implying that this protein used as a virulent factor uniquely impacts the prophenoloxidase cascade.

Molecular characterization and expression profiling of ryanodine receptor gene in the pink stem borer, Sesamia inferens (Walker).

The susceptibilities of three field populations of pink stem borer (PSB), Sesamia inferens (walker) to diamide insecticides, chlorantraniliprole and flubendiamide, were evaluated in this study. The results showed that these PSB field populations were still sensitive to the two diamide insecticides after many years of exposure. To further understand PSB and diamide insecticide, the full-length ryanodine receptor (RyR) cDNA (named as SiRyR), the molecular target of diamide insecticides was cloned from PSB and characterized. The SiRyR gene contains an open reading frame of 15,420 nucleotides, encoding 5140 amino acid residues, which shares 77% to 98% sequence identity with RyR homologous of other insects. All hallmarks of RyR proteins are conserved in the SiRyR protein, including the conserved C-terminal domain with the consensus calcium-biding EF-hands (calcium-binding motif), the six transmembrane domains, as well as mannosyltransferase, IP3R and RyR (pfam02815) (MIR) domains. Real-time qPCR analysis revealed that the highest mRNA expression levels of SiRyR were observed in pupa and adults, especially in males. SiRyR was expressed at the highest level in thorax, and the lowest level in wing. The full genetic characterization of SiRyR could provide useful information for future functional expression studies and for discovery of new insecticides with selective insecticidal activity.

Copper-Catalyzed Decarboxylative Difluoroalkylation and Perfluoroalkylation of α,ß-Unsaturated Carboxylic Acids.

Copper-catalyzed decarboxylative difluoroalkylation and perfluoroalkylation of α,ß-unsaturated carboxylic acids is described. Promoted by dialkyl phosphite, this novel reaction affords fluoroalkylated motifs with excellent stereoselectivity and broad substrate scope under mild reaction conditions from readily available fluoroalkyl iodides and bromides. Preliminary mechanism study suggests that radical pathway was involved in the catalytic cycle and dialkyl phosphite had played an indispensable role in this reaction.

Electrochemical Decarboxylative Sulfonylation of Cinnamic Acids with Aromatic Sulfonylhydrazides to Vinyl Sulfones.

A stereoselective synthesis of (E)-vinyl sulfones has been developed via electrochemical oxidative N-S bond cleavage of aromatic sulfonylhydrazides, followed by cross-coupling reactions with cinnamic acids to form the C-S bond. The protocol proceeded smoothly to afford (E)-vinyl sulfones in good yields with wide substrate scope under metal-free and halogen-free conditions.

Electrochemical Oxidative C-H/N-H Coupling between γ-Lactams and Anilines.

A mild method for the direct C-H/N-H coupling between γ-lactams and anilines through electrochemical oxidation has been developed. The protocol proceeded smoothly without metal catalysts at room temperature to afford γ-substituted γ-lactams in good yields. It has been revealed that the quasi-divided cell which provided high current density on the anode was crucial for this reaction.

Electrochemical Synthesis of Benzazoles from Alcohols and o-Substituted Anilines with a Catalytic Amount of Co(II) Salt.

An electrochemical synthesis of benzazoles directly from alcohols and o-substituted anilines has been developed. The reaction conditions have been optimized by varying the composition of the electrolyte and the metal salt used as catalyst. The cyclization proceeds smoothly with a catalytic amount of a cobalt salt under air at room temperature to afford 2-substituted benzimidazoles, benzothiazoles, and benzoxazoles in good to excellent yields with a wide substrate scope.

Electrochemical cleavage of aryl ethers promoted by sodium borohydride.

The NaBH4 (or TBABH4)-promoted electrochemically reductive cleavage of aryl C-O bonds in diaryl ethers to produce phenols and arenes with high yields and excellent selectivities at room temperature was reported. Air- and water-tolerable, this process also works on the cleavage of aryl alkyl and benzyl ethers. The application to break the ß-O-4, α-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion.

Multimodal Imaging-Guided Synergistic Photodynamic Therapy Using Carbonized Zn/Co Metal-Organic Framework Loaded with Cytotoxin Against Liver Cancer.

Purpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.

A metal-organic framework (MOF) built on surface-modified Cu nanoparticles eliminates tumors via multiple cascading synergistic therapeutic effects.

Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl-d-tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8+ and CD4+ T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen (1O2) upon specific laser irradiation to effectively kill tumor cells. CaO2 on the outer layer generated oxygen (O2) and hydrogen peroxide (H2O2) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H2O2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment.

Electrochemical technique and copper-promoted transformations: selective hydroxylation and amination of arylboronic acids.

An efficient and selective electrosynthesis of phenols and anilines from arylboronic acids in aqueous ammonia is achieved in an undivided cell. By simply changing the concentration of aqueous ammonia and the anode potential, good yields of phenols and anilines can be obtained chemoselectively with high reaction rates. We propose that anodic oxidation could have played an important role in these transformations.

Electrochemical Decarboxylative Silylation of α,ß-Unsaturated Carboxylic Acids.

An electrochemical method for the decarboxylative silylation of α,ß-unsaturated carboxylic acids was developed. A variety of alkenylsilanes could be obtained in satisfactory yields and excellent selectivities under external oxidant- and metal-free conditions. Mechanistic studies showed that the formation of the silyl radical was mediated by NHPI, which produces the hydrogen atom transfer (HAT) reagent phthalimide N-oxyl (PINO) via multiple-site concerted proton-electron transfer (MS-CPET).

Characterization of Six Diamide Insecticides on Ryanodine Receptor: Resistance and Species Selectivity.

Ryanodine receptor (RyR) has been used as an insecticide target to control many destructive agricultural pests. The effectiveness of these insecticides has been limited by the spread of resistance mutations identified in pest RyRs, but the detailed molecular impacts of the individual mutations on the activity of different diamide compounds have not been fully explored. We created five HEK293 cell lines stably expressing wild type rabbit RyR1, wild type Spodoptera frugiperda RyR (Sf RyR), or Sf RyR carrying different resistance mutations, including G4891E, G4891E/I4734M, and Y4867F, respectively. R-CEPIA1er, a genetically encoded fluorescent protein, was also introduced in these cell lines to report the Ca2+ concentration in the endoplasmic reticulum. We systematically characterized the activities of six commercial diamide insecticides against different RyRs using the time-lapse fluorescence assay. Among them, cyantraniliprole (CYAN) displayed the highest activity against all three resistant Sf RyRs. The good performance of CYAN was confirmed by the toxicity assay using gene-edited Drosophila expressing the mutant RyRs, in which CYAN showed the lowest LD50 value for the double resistant mutant. In addition, we compared their acitivty between mammalian and insect RyRs and found that flubendiamide has the best insect-selectivity. The mechanism of the anti-resistance property and selectivity of the compounds was proposed based on the structural models generated by homology modeling and molecular docking. Our findings provide insights into the mechanism of insect resistance and guidance for developing effective RyR agonists that can selectively target resistant pests.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

Iodine mediated/Brønsted acid-catalyzed dimerization of vinylarenes: a tandem reaction through Ritter trapping to produce N-(4-iodo-1,3-diarylbutyl) acetamides.

In the presence of p-toluenesulfonic acid and iodine, styrene derivatives undergo head-to-tail dimerization followed by trapping with nitriles to yield the corresponding Ritter-type products.

Electrosynthesis of (hetero)aryl nitriles from α-imino-oxy acids via oxidative decarboxylation/N-O cleavage.

A new method for the synthesis of (hetero)aryl nitriles via iminyl radicals has been developed through the electrochemical oxidative decarboxylation of α-imino-oxy acids. This protocol provides an efficient approach to nitriles with a broad range of functional-group tolerance under ambient conditions and can be applied for one-pot gram-scale synthesis.