Separation and detection of cyproconazole enantiomers and its stereospecific recognition with chiral stationary phase by high-performance liquid chromatography.

Cyproconazole, a chiral triazole fungicide, has been diffusely used and analyzed. The development of an effective analytical method for cyproconazole enantiomers can support their residual monitoring and risk assessment. In the present study, the absolute configuration of the cyproconazole enantiomers was confirmed by electronic circular dichroism and time-dependent density functional theory. The enantioseparation parameters were optimized by the response surface methodology using the Box-Behnken design on Lux Cellulose-2. The elution order of (2S,3R)-(+)-, (2S,3S)-(+)-, (2R,3S)-(-)-, and (2R,3R)-(-)-cyproconazole was simulated with molecular docking. The enantiomers were completely separated primarily via halogen bond and hydrogen bond interactions with the chiral stationary phases. The mean recoveries of the cyproconazole enantiomers in the four matrices were 71.8-102.0% with intraday relative standard deviations (RSDs) of 0.3-11.9% and interday RSDs of 0.9-10.6%. The results showed the chiral recognition mechanism clearly and confirmed that the method was accurate and convenient for the simultaneous detection of cyproconazole enantiomers in environmental and food matrices.

Stereoselective bioactivity of the chiral triazole fungicide prothioconazole and its metabolite.

Chiral triazole fungicides have played a significant role in plant pathogen control. Although their enantiomers often exhibit different bioactivity, the mechanism of the stereoselectivity has not been well studied. The stereoselective bioactivity and mechanisms of prothioconazole and its chiral metabolite against plant pathogenic fungi were investigated. The results indicated that the metabolite exerted more fungicidal activities than the activities of the parent compound. R-Prothioconazole and R-prothioconazole-desthio were 6-262 and 19-954 times more potent against pathogenic fungi than the S-enantiomers, respectively. The R-enantiomers were more effective than in inhibiting the biosynthesis of ergosterol and deoxynivalenol the S-enantiomer. Homology modeling and molecular docking suggested that the R-enantiomers of prothioconazole and prothioconazole-desthio possessed better binding modes than S-enantiomers to CYP51B. Moreover, exposure to prothioconazole and its metabolite enantiomers significantly changed the transcription levels of the CYP51 (CYP 51A, CYP51B, CYP 51C) and Tri (Tri5, Tri6, Tri12) genes. The results showed that application of the R-prothioconazole could require a smaller application amount to eliminate the carcinogenic mycotoxins and any environmental risks.

Effects of Exposure to Different Types of Metal-Organic Framework Nanoparticles on the Gut Microbiota and Liver Metabolism of Adult Zebrafish.

Metal-organic framework nanoparticles (MOF NPs) have received much attention for their potential use in nanopesticides. However, little is known about the potential health and environmental risks associated with these materials. In this study, the toxicological responses of zebrafish exposed to five MOF NPs for short and long periods of time were evaluated. The acute toxicity results showed that the toxicity of the five MOF NPs to zebrafish embryos and adult zebrafish was in the order of Cu-MOF > ZIF-90 > ZIF-8 > Fe-MOF > Zr-MOF. Histopathological analysis revealed that ZIF-8, ZIF-90, and Cu-MOF NPs caused liver swelling and vacuolization in zebrafish. The cellular ultrastructure showed that ZIF-8, ZIF-90, and Cu-MOF NPs severely damaged the mitochondrial structure in intestinal epithelial cells and liver cells. The 16S rDNA sequencing data showed that all five MOF NPs significantly altered the dominant microorganisms in the zebrafish intestine. The microbial markers of intestinal inflammation, Proteobacteria (Aeromonas, Plesiomonas, and Legionella), were significantly increased in the Fe-MOF, ZIF-8, Zr-MOF, and Cu-MOF treatment groups. Metabolomics results indicated that the levels of inflammatory promoting factors (Leukotriene E4, 20-hydroxyeicosatetraenoic acid) in arachidonic acid metabolism were decreased, and the levels of inflammatory suppressing factors (8,9-epoxyeicosatrienoic acid) were increased. Metabolites related to oxidative stress, such as glutamine, pyridoxamine, and l-glutamic acid in vitamin B6 metabolism and other signaling pathways, were significantly reduced. Overall, these results suggest that the different MOF NPs had widely varying toxicity to zebrafish, and further attention should be paid to the toxicity of MOF NPs in the real environment.

pH-responsive λ-cyhalothrin nanopesticides for effective pest control and reduced toxicity to Harmonia axyridis.

In this study, pH-responsive LC@O-CMCS/PU nanoparticles were prepared by encapsulating λ-cyhalothrin (LC) with O-carboxymethyl chitosan (O-CMCS) to form LC/O-CMCS and then covering it with polyurethane (PU). Characterization and performance test results demonstrate that LC@O-CMCS/PU had good alkaline release properties and pesticide loading performance. Compared to commercial formulations containing large amounts of emulsifiers (e.g., emulsifiable concentrate, EC), LC@O-CMCS/PU showed better leaf-surface adhesion. On the dried pesticide-applied surfaces, the acute contact toxicity of LC@O-CMCS/PU to Harmonia axyridis (H. axyridis) was nearly 20 times lower than that of LC EC. Due to the slow-releasing property of LC@O-CMCS/PU, only 16.38 % of LC was released at 48 h in dew and effectively reduced the toxicity of dew. On the pesticide-applied leaves with dew, exposure to the LC (EC) caused 86.66 % mortality of H. axyridis larvae significantly higher than the LC@O-CMCS/PU, which was only 16.66 % lethality. Additionally, quantitative analysis demonstrated 11.33 mg/kg of λ-cyhalothrin in the dew on LC@O-CMCS/PU lower than LC (EC) with 4.54 mg/kg. In summary, LC@O-CMCS/PU effectively improves the safety of λ-cyhalothrin to H. axyridis and has great potential to be used in pest control combining natural enemies and chemical pesticides.

ß-Glucan-Functionalized Mesoporous Silica Nanoparticles for Smart Control of Fungicide Release and Translocation in Plants.

In this work, an enzyme-responsive nanovehicle for improving captan (CAP) contact fungicide bioactivity and translocation in plant tissues was synthesized (CAP-MSNs-ß-glucan) by attaching ß-glucan to the outer surface of mesoporous silica nanoparticles. CAP-MSNs-ß-glucan properties were tested by FTIR, ζ-potential, DLS, XRD, TGA, FE-SEM, and HR-TEM. Cargo protection ability of CAP-MSNs-ß-glucan from photolysis and hydrolysis was examined in comparison to CAP commercial formulation (CAP-CF). CAP-MSNs-ß-glucan distribution in plant tissues, bioactivity against Fusarium graminearum, and biotoxicity toward zebrafish (Danio rerio) were tested and compared with that of CAP-CF. CAP-MSNs-ß-glucan results showed good loading efficacy reaching 18.39% and enzymatic-release dependency up to 83.8% of the total cargo after 20 days of ß-glucan unsealing. CAP-MSNs-ß-glucan showed significant release protection under pH changes. MSNs-ß-glucan showed excellent CAP protection from UV. CAP-MSNs-ß-glucan showed better distribution in corn tissues and 1.28 more inhibiting potency to Fusarium graminearum than CAP-CF. CAP-MSNs-ß-glucan showed 1.88 times lower toxicity than CAP-CF to zebrafish after 96 h of treatment. We recommend using such formulations to overcome shortcomings of contact fungicides and achieve better and sustainable farming.

Efficiency of mesoporous silica/carboxymethyl ß-glucan as a fungicide nano-delivery system for improving chlorothalonil bioactivity and reduce biotoxicity.

Understanding the lethal effects of pesticides nano formulations on the targeted organisms (pathogens) and the non-targeted organisms (fish, earthworms, etc) is essential in assessing the probable impact of new technologies on agriculture and environment. Here we evaluated the bioactivity and the biotoxicity of new type of fungicide smart-delivery formulation based on conjugating carboxymethylated-ß-glucans on the mesoporous silica nanoparticles (MSNs) surface after loading chlorothalonil (CHT) fungicide in the MSNs pores. The obtained formulation has been characterized with FE-SEM, and HR-TEM. The CHT loading efficiency has been measured with TGA. The bioactivity of the obtained formulation (CHT@MSNs-ß-glucans) has been tested against four pathogens, fusarium head blight (Fusarium graminearum), sheath rot (Sarocladium oryzae), rice sheath blight (Rhizoctonia solani), and soyabean anthracnose (Colletotrichum truncatum) compared with CHT WP 75% commercial formulation (CHT-WP) and technical CHT. The environmental biotoxicity of CHT@MSNs-ß-glucans compared with CHT-WP has been tested toward earthworm (Eisenia fetida) and zebra fish (Danio rerio). The results showed that CHT@MSNs-ß-glucans has an excellent bioactivity against the subjected pathogens with better inhabiting effects than CHT-WP. CHT@MSNs-ß-glucans toxicity to Eisenia fetida was found 2.25 times lower than CHT-WP toxicity. The LC50 of CHT@MSNs-ß-glucans to zebra fish after the first 24h was 2.93 times higher than CHT-WP. After 96h of treatment, the LC50 of CHT@MSNs-ß-glucans was 2.66 times higher than CHT-WP. This work highlighted the necessity to increase the mandatory bioassays of nano formulations with the major non-target organisms in the environmental risk assessment of new pesticide formulations.

Preparation of alginate-chitosan floating granules loaded with 2-methyl-4-chlorophenoxy acetic acid (MCPA) and their bioactivity on water hyacinth.

BACKGROUND: Water hyacinth (Eichhornia crassipes) is considered the most damaging aquatic weed in many countries. Chemical methods are still the primary approach to control, although this directly exposes the natural enemy of water hyacinth (water hyacinth weevil) to herbicides. In addition, spray drift can easily damage non-target plants. In this study, herbicides, natural polymer materials (chitosan and carboxymethyl chitosan), sodium alginate and natural oils (citronella oil) were used to prepare novel floating polysaccharide granules as a solution for controlling water hyacinth. RESULTS: 2-Methyl-4-chlorophenoxy acetic acid (MCPA) floating granules with a spherical structure were prepared using a MCPA-chitosan-sodium alginate-oil cross-linking and embedding method. The granules produced showed the required properties of floatation and slow controlled herbicide release. In addition, the polysaccharide granules collected around water hyacinth plants and enabled targeted release of the active herbicide ingredients onto the stems and roots of the weed, thereby stopping the herbicide from reaching non-target plants and preventing regrowth of water hyacinth. CONCLUSION: We successfully prepared highly effective MCPA-loaded floating granules, which compared with an MCPA solution, exerted greater control on water hyacinth. Concomitantly, these granules provide a solution to spray drift and ensure the safety of natural enemies of water hyacinth, which is of great significance in research on herbicide formulations.

Changes in soil and rat gut microbial diversity after long-term exposure to the chiral fungicide epoxiconazole.

In previous articles, it was found that epoxiconazole enantiomers can persist for a long time in the environment, causing severe environmental damage. Herein, we investigated alterations in the soil microbial community and rat gut microbiota after six weeks of treatment with rac-epoxiconazole or one of its enantiomers. The selected concentrations were 1, 2, and 6 times greater than the maximum residue limits (MRLs). The rat gut microbiota relative abundance in the feces significantly changed following exposure to rac-epoxiconazole or one of its enantiomers. At the phylum level, in the R,S-, S,R-epoxiconazole, and rac-treated groups, Firmicutes presented the greatest decrease in abundance; however, Spirochaetes presented the greatest increase in abundance in the rac- and S,R-epoxiconazole-treated groups. In response to R,S-epoxiconazole, Epsilonbacteraeota presented the greatest increase in abundance. In soil samples treated with epoxiconazole, the relative abundance of the soil bacterial community also changed. Proteobacteria presented the greatest decrease in abundance in the S,R- and rac-treated samples. However, Firmicutes presented the greatest increase in abundance. In the R,S-treated soil samples, the situation was the opposite. In general, prolonged exposure to epoxiconazole at high concentrations could initiate noticeable alterations in rat gut microbiota and soil microbial diversity. R,S-epoxiconazole had improved bioactivity and less toxic effects at relatively low concentrations. Therefore, we recommend using R,S-epoxiconazole at a relatively low concentration, which is better for environmental safety.

Carboxylated ß-cyclodextrin anchored hollow mesoporous silica enhances insecticidal activity and reduces the toxicity of indoxacarb.

In this study, a pesticide controlled release system with dual response characteristics of pH and enzyme triggering was developed. Indoxacarb (IDC) was loaded into hollow mesoporous silica (HMS) nanoparticles, carboxylated ß-cyclodextrin (ß-CD) acted as a capping molecule to couple with the amino-functionalized HMS, and their well-defined morphological structures were confirmed by scanning electron microscopy and transmission electron microscopy. The results showed that the prepared IDC loaded HMS-CD had high loading efficiency (26.42%, w/w) and showed excellent dual response properties to pH and the α-amylase enzyme. IDC loaded HMS-CD nanoparticles showed better insecticidal activity against Spodoptera frugiperda than applying the same dose of IDC emulsifiable concentrate, and the toxicity of IDC loaded HMS-CD to zebrafish was reduced by more than 5-fold, indicating that insecticide delivery systems based on ß-CD-anchored HMS nanoparticles could potentially be applied for sustainable control of pests and reduce harm to non-target organisms and the environment.

Stereoselective bioactivity, toxicity and degradation of the chiral triazole fungicide bitertanol.

BACKGROUND: The chiral pesticide bitertanol has been widely used in the prevention and treatment of fungal diseases on many crops. However, research on bitertanol at the stereoisomer level has not been reported. Here, we study the stereoselective bioactivity, toxicity, and degradation of this pesticide under laboratory and field conditions. RESULT: (1S,2R)-Bitertanol was the most effective stereoisomer, showing 4.3-314.7 times more potent bioactivity than other stereoisomers against eight target pathogenic fungi. (1S,2R)-Bitertanol showed 10.2 times greater inhibition of Botrytis cinerea spore germination than (1R,2S)-bitertanol. According to the receptor-drug docking results, the distances from the nitrogen atom in the heterocycle of (1S,2R)-, (1R,2S)-, (1R,2R)-, and (1S,2S)-bitertanol to the central Fe + atoms in the ferriporphyrin were 2.5, 3.8, 2.6, and 3.8 Å, respectively. (1S,2S)-Bitertanol was 1.6-2.7 times more toxic than (1R,2R)-bitertanol to Chlorella pyrenoidosa. The half-lives of (1R,2S)-, (1S,2R)-, (1R,2R)-, and (1S,2S)-bitertanol were 3.7, 4.1, 4.1, and 4.8 d, respectively, in tomato. CONCLUSION: The stereoselective bioactivity, toxicity, and degradation for bitertanol were first studied here. (1S,2R)-Bitertanol was a high efficiency and low toxicity stereoisomer. Moreover, the stereoselective bioactivity among all stereoisomers correlated with the binding distances and calculated energy differences between stereoisomers and the target protein. This study also provides a foundation for a systematic evaluation of bitertanol at the stereoisomer level. © 2019 Society of Chemical Industry.