prothioconazole and triticonazole

Triazole fungicides with one or two chiral centers are widely used worldwide. The liver microsomes plays a major role in the metabolism and systemic elimination of chiral pesticides after exposure. In this present work, enantioselective metabolism of four representative chiral triazole fungicides (prothioconazole, flutriafol, triticonazole, and epoxiconazole) in rat liver microsomes (RLM) was investigated using LC-MS/MS. Baseline separation of the four chiral fungicides and prothioconazole-desthio was achieved on Lux-cellulose-1. The results demonstrated that the R-enantiomers of flutriafol and triticonazole were preferentially metabolized with half-life ranged from 17.33 min to 99.00 min. The R,S-epoxiconazole accumulated with a half-life of 173.25 min. There was no stereoselectivity for prothioconazole. However, remarkable stereoselective metabolism was observed for prothioconazole-desthio. The results of enzyme kinetic revealed different affinities between the enantiomers and metabolic enzymes. In addition, homologous modeling and molecular docking results indicated that enantioselectivity were partially to enantiospecific binding affinities with CYP enzymes. This study highlights a new quantitative approach for stereoselective metabolism of chiral agrochemicals and provides more accurate data on risk assessment of triazole fungicides.

Topics: Animals; Chromatography, High Pressure Liquid; Cyclopentanes; Epoxy Compounds; Fungicides, Industrial; Microsomes, Liver; Molecular Docking Simulation; Rats; Stereoisomerism; Tandem Mass Spectrometry; Triazoles

Triticonazole and prothioconazole are widely used systemic agricultural triazole fungicides both with a chiral center. In this work, the enantioselective degradation of triticonazole and prothioconazole in three types of soils were investigated under native conditions using reversed phase liquid chromatography-tandem mass spectrometry with a Chiralcel OD-RH column. The results indicated that the enantioselective degradation was observed with S-triticonazole and R-prothioconazole preferentially degraded and the degradation rate was fast with a half-life within 6 days. It was also found that the presence of earthworms can accelerate the degradation and further enhance degradation enantioselectivity of triticonazole and prothioconazole in soils. Moreover, the enantioselective of triticonazole and prothioconazole in earthworms were studied. The results showed that the bioaccumulation was enantioselective with R-triticonazole and S-prothioconazole preferentially accumulated, which was similar to the soil. Our findings suggest that the enantioselective toxicity and potential effects of the metabolites should be considered for more accurate assessment of ecological risks of triticonazole and prothioconazole to target and non-target species.

Topics: Animals; Biodegradation, Environmental; Cyclopentanes; Fungicides, Industrial; Oligochaeta; Soil; Soil Pollutants; Stereoisomerism; Triazoles