Pd-NHC (NHC = N-Heterocyclic Carbene)-Catalyzed B-Alkyl Suzuki Cross-Coupling of 2-Pyridyl Ammonium Salts by N-C Activation: Application to the Discovery of Agrochemical Molecular Hybrids.

2-Alkylpyridines are a privileged scaffold throughout the realm of organic synthesis and play a key role in natural products, pharmaceuticals, and agrochemicals. Herein, we report the first B-alkyl Suzuki cross-coupling of 2-pyridyl ammonium salts to access functionalized 2-alkylpyridines. The use of well-defined, operationally simple Pd-NHCs permits for an exceptionally broad scope of the challenging B-alkyl C-N cross-coupling with organoboranes containing ß-hydrogen, representing a novel method for the discovery of highly sought-after molecules for plant protection.

Coenzyme Q10 Stimulate Reproductive Vatality.

Female infertility and pregnancy maintenance are associate with various factors, including quantity and quality of oocytes, genital inflammation, endometriosis, and other diseases. Women are even diagnosed as unexplained infertility or unexplained recurrent spontaneous abortion when failed to achieve pregnancy with current treatment, which are urgent clinical issues need to be addressed. Coenzyme Q10 (CoQ10) is a lipid-soluble electron carrier in the mitochondrial electron transport chain. It is not only essential for the mitochondria to produce energy, but also function as an antioxidant to maintain redox homeostasis in the body. Recently, the capacity of CoQ10 to reduce oxidative stress (OS), enhance mitochondrial activity, regulate gene expression and inhibit inflammatory responses, has been discovered as a novel adjuvant in male reproductive performance enhancing in both animal and human studies. Furthermore, CoQ10 is also proved to regulate immune balance, antioxidant, promote glucose and lipid metabolism. These properties will bring highlight for ovarian dysfunction reversing, ovulation ameliorating, oocyte maturation/fertilization promoting, and embryonic development optimizing. In this review, we systematically discuss the pleiotropic effects of CoQ10 in female reproductive disorders to investigate the mechanism and therapeutic potential to provide a reference in subsequent studies.

Suzuki-Miyaura Cross-Coupling of 2-Pyridyl Trimethylammonium Salts by N-C Activation Catalyzed by Air- and Moisture-Stable Pd-NHC Precatalysts: Application to the Discovery of Agrochemicals.

We report the first Suzuki-Miyaura cross-coupling of 2-pyridyl ammonium salts by highly selective N-C activation catalyzed by air- and moisture-stable Pd(II)-NHC (NHC = N-heterocyclic carbene) precatalysts. The use of well-defined and highly reactive [Pd(IPr)(3-CF3-An)Cl2] (An = aniline) or [Pd(IPr)(cin)Cl] (cin = cinnamyl) Pd(II)-NHC catalysts permits an exceptionally broad scope of the cross-coupling to furnish valuable biaryl and heterobiarylpyridines that are ubiquitous in medicinal chemistry and agrochemistry research. The overall process leverages the Chichibabin C-H amination of pyridines with N-C activation to enable an attractive strategy to the 2-pyridyl problem. The utility of the method to the discovery of potent agrochemicals is presented. Considering the importance of 2-pyridines and the versatility of N-C activation methods, we envision that this new C-H/N-C activation strategy will find broad application.

Structural Diversity Design, Synthesis, and Insecticidal Activity Analysis of Ester-Containing Isoxazoline Derivatives Acting on the GABA Receptor.

To explore insecticides targeting the γ-aminobutyric acid (GABA) receptor, two series of novel isoxazoline derivatives containing sulfonic and carboxylic esters were designed and synthesized. Their insecticidal activities against Plutella xylostella, Mythimna separata, and Aedes aegypti larvae and their structure-activity relationship were investigated. The sulfonate-containing isoxazoline derivatives (10k-q) exhibited promising insecticidal activities against the three insect larvae. Compound 10o displayed excellent activities with LC50 values of 8.32, 5.23, and 0.35 µg/mL at 48 h against P. xylostella, M. separata, and A. aegypti larvae, respectively, which were better than or similar to those of avermectin. Furthermore, compound 10o exhibited a faster insecticidal effect than avermectin against M. separata. The mode of action of 10o was preliminarily verified by molecular docking, theoretical calculations, and measurement of glutamate decarboxylase and glutamic pyruvic transaminase activities. Compound 10o is a novel insecticidal candidate acting on GABA receptors, which could guide the discovery of isoxazoline insecticides.

Determination of bacterial toxin toxoflavin and fervenulin in food and identification of their degradation products.

A method using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of toxoflavin and fervenulin in 6 types of food.The limits of detection (LODs, S/N ≥ 3) of toxoflavin and fervenulin reached 12 µg/kg and 24 µg/kg, respectively.The recoveries ranged from 70.1 % to 108.7 %.Intra-day RSDs (n = 5) and inter-day RSDs (n = 3) ranged from 0.9 % to 9.5 %.The method was successfully applied to analyse 36 samples, and one Tremella fuciformis Berk. sample was found with 7.5 mg/kg toxoflavin and 3.2 mg/kg fervenulin. Toxoflavin and fervenulin were acidic compounds and easily degraded in 0.1 % ammonia solution (v/v),degradation products were identified by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS).

Sonogashira Cross-Coupling of Aryl Ammonium Salts by Selective C-N Activation Catalyzed by Air- and Moisture-Stable, Highly Active [Pd(NHC)(3-CF3-An)Cl2] (An = Aniline) Precatalysts.

We report the Sonogashira cross-coupling of aryl ammonium salts catalyzed by air- and moisture-stable [Pd(NHC)(3-CF3-An)Cl2] (An = aniline). This highly active Pd(II)-NHC complex features broad scope and excellent C-N activation selectivity in the challenging alkynylative cross-coupling of aryl ammonium salts. Full structural characterization and computational studies demonstrate the effect of pyridine to aniline replacement as highly effective stabilizing ancillary ligand in well-defined Pd(II)-NHCs. Considering the high reactivity and the recent commercialization of [Pd(NHC)(3-CF3-An)Cl2] (Millipore Sigma, no. 915165), this catalyst represents an attractive approach to the activation of C-N bonds of broad synthetic interest.

CL6mN: Rationally Designed Optogenetic Photoswitches with Tunable Dissociation Dynamics.

The field of optogenetics uses genetically encoded photoswitches to modulate biological phenomena with high spatiotemporal resolution. We report a set of rationally designed optogenetic photoswitches that use the photolyase homology region of A. thaliana cryptochrome 2 (Cry2PHR) as a building block and exhibit highly efficient and tunable clustering in a blue-light dependent manner. CL6mN (Cry2-mCherry-LRP6c with N mutated PPPAP motifs) proteins were designed by mutating and/or truncating five crucial PPP(S/T)P motifs near the C-terminus of the optogenetic Wnt activator Cry2-mCherry-LRP6c, thus eliminating its Wnt activity. Light-induced CL6mN clusters have significantly greater dissociation half-lives than clusters of wild-type Cry2PHR. Moreover, the dissociation half-lives can be tuned by varying the number of PPPAP motifs, with the half-life increasing as much as 6-fold for a variant with five motifs (CL6m5) relative to Cry2PHR. Finally, we demonstrate the compatibility of CL6mN with previously reported Cry2-based photoswitches by optogenetically activating RhoA in mammalian cells.

One-pot synthesis of heterodimeric agonists that activate the canonical Wnt signaling pathway.

Fragment antigen-binding domains (Fabs) from anti-Frizzled and anti-LRP6 monoclonal antibodies were conjugated using SpyTag-SpyCatcher chemistry via a one-pot reaction. The resulting synthetic heterodimeric agonist outperformed the natural ligand, Wnt-3a, in activating canonical Wnt signaling in mammalian cells. This approach should be broadly applicable to activate receptor-mediated cellular signaling.

Individual High-Quality N-Doped Carbon Nanotubes Embedded with Nonprecious Metal Nanoparticles toward Electrochemical Reaction.

Developing highly active and stable nonprecious metal catalysts for electrochemical reactions is desirable but remains a great challenge. Herein, we report a novel metal-ion adsorption-pyrolysis strategy for the controllable zeolitic imidazolate framework-8 derived synthesis of individual high-quality N-doped carbon nanotubes embedded with well-dispersed nonprecious metal nanoparticles, which exhibit superior electrocatalytic activity and stability for electrochemical CO2 reduction reaction, oxygen reduction reaction, and oxygen evolution reaction. Experimental analysis and density functional theory calculations indicate that the remarkable electrocatalytic activities are mainly attributed to the interface effects for the efficient electron transfer from metal nanoparticles to the N-doped carbon shell, as well as the large specific areas, unique tube structures, appropriate doping, high graphitization degree, and robust frameworks. The high reaction stability is attributed to the multiwalled graphitic carbon shells efficiently preventing metal nanoparticles from aggregation, corrosion, and oxidation. This novel synthetic strategy presents a facile universality for synthesizing N-doped carbon nanotube structures and will provide a guideline for developing low-cost, highly active, and stable electrocatalytic materials for sustainable energy conversion.