Enantioselective effects of chiral prothioconazole and its metabolites: Oxidative stress in HepG2 cells and lysozyme activity.

Chiral pesticides may exhibit enantioselectivity in terms of bioconcentration, environmental fate, and reproductive toxicity. Here, chiral prothioconazole and its metabolites were selected to thoroughly investigate their enantioselective toxicity and mechanisms at the molecular and cellular levels. Multispectral techniques revealed that the interaction between chiral PTC/PTCD and lysozyme resulted in the formation of a complex, leading to a change in the conformation of lysozyme. Meanwhile, the effect of different conformations of PTC/PTCD on the conformation of lysozyme differed, and its metabolites were able to exert a greater effect on lysozyme compared to prothioconazole. Moreover, the S-configuration of PTCD interacted most strongly with lysozyme. This conclusion was further verified by DFT calculations and molecular docking as well. Furthermore, the oxidative stress indicators within HepG2 cells were also affected by chiral prothioconazole and its metabolites. Specifically, S-PTCD induced more substantial perturbation of the normal oxidative stress processes in HepG2 cells, and the magnitude of the perturbation varied significantly among different configurations (P > 0.05). Overall, chiral prothioconazole and its metabolites exhibit enantioselective effects on lysozyme conformation and oxidative stress processes in HepG2 cells. This work provides a scientific basis for a more comprehensive risk assessment of the environmental behaviors and effects caused by chiral pesticides, as well as for the screening of highly efficient and less biotoxic enantiomeric monomers.

Enantioselective effect of chiral prothioconazole on the conformation of bovine serum albumin.

As a typical chiral triazole fungicide, the enantioselective toxicity of prothioconazole to environmental organisms is of increasing concern. Herein, the binding mechanism of chiral PTCs to BSA was investigated by multi-spectral technique and molecular docking. Fluorescence titration and fluorescence lifetime experiments fully established that quenching BSA fluorescence by chiral PTCs is static quenching and could spontaneously bind to BSA. Hydrophobic interactions dominate the binding process of chiral PTCs to BSA. Differently, although both chiral PTCs and BSA have a primary binding site, the difference in chiral isomerism leads to a stronger binding ability of S-PTC than R-PTC. Both configurations of PTC can change the conformation of BSA and induce changes in the microenvironment around its amino acid residues, and the effect of S-PTC is more significant. Overall, S-PTC exhibited a more substantial effect on BSA structure relative to R-PTC. That is, S-PTC may lead to more potent potential toxicological effects on environmental organisms. This study provides a comprehensive assessment of the environmental behavior of chiral pesticides and their potential toxicity to environmental organisms at the molecular level and provides a theoretical basis for the screening of highly effective and biologically less toxic enantiomers of chiral pesticides.