Absolute Configuration, Enantioselective Bioactivity, And Degradation Of The Novel Chiral Triazole Fungicide Mefentrifluconazole

Mefentrifluconazole is a new chiral triazole fungicide with a pair of enantiomers. However, the enantioselective differences in the biological effects and environmental behaviors of mefentrifluconazole are unclear. In the present work, a new simultaneous determination method of mefentrifluconazole enantiomers was established using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The absolute configuration of the two mefentrifluconazole enantiomers was confirmed by comparing the experimental and calculated ECD spectra. The enantioselective bioactivity to target fungi and degradation in cucumber samples were also assessed. The absolute configurations of the two enantiomers eluted on the Superchiral IG-3 column were confirmed as R-(-)-mefentrifluconazole and S-(+)-mefentrifluconazole. The R-(-)-mefentrifluconazole possessed 5-473 times higher bioactivity than S-(+)-mefentrifluconazole toward six kinds of target pathogenic fungi. In addition, R-(-)-mefentrifluconazole exhibited stronger efficacy of suppression of ergosterol biosynthesis. The molecular docking results indicated that R-(-)-mefentrifluconazole had shorter binding distances and lower energies with the target protein than S(+)-mefentrifluconazole, which may result in the enantioselective bioactivity. The high-efficiency enantiomer of R(-)-mefentrifluconazole has longer duration in cucumber samples due to the relatively long half-life of 4.0 days. This research has clarified the bioactivity differences and mechanism between mefentrifluconazole enantiomers against target fungi and laid the foundation for an in-depth study of mefentrifluconazole at the chiral level.