A systematic evaluation of zoxamide at enantiomeric level

Abstract

Zoxamide is a recently discovered chiral fungicide that applied to agricultural production, but the potential environmental risk may be underestimated because the risk posed by either enantiomer has not been adequately assessed. Therefore, systemic evaluation of zoxamide was first carried out at the enantiomeric level. Enantioselective bioactivity against target pathogens (Phytophthora capsici Leonian, Alternaria solani, Botryis cinerea, Colletotrichum gloeosprioides Penz, Phytophthora sojae Kaufmann & Gerdemann) was explored, and the order of the bioactivity was R-zoxamide >Rac-zoxamide >S-zoxamide, with a 9.9- to 140.0-times difference between two enantiomers. Molecular docking simulation was utilized to clarify the mechanism underlying the observed differences in enantioselective bioactivity, and the result indicated that a difference of Van der waals force between R/S-zoxamide and the specific receptor gave rise to the different antifungal activity. The enantioselective toxicity result demonstrated that R-zoxamide had 4.9- to 10.8- times greater acute toxicity to Selenastrum capricornutum and Daphnia magna than S-zoxamide. S-zoxamide degraded faster under aerobic condition in all three types of soils, giving rise to an enrichment of high-risk R-enantiomer. Under anaerobic condition, however, no significant difference in dissipation rate was observed between two enantiomers. R-zoxamide was 1.5- to 3.5-times more bioactive and 1.1- to 1.5-times more toxic than Rac-zoxamide, which means developing R-zoxamide instead of racemate is a potential way to reduce pesticide dosage without loss of efficacy against target organisms and that an inactive isomer would no more be released to the environment. This study may have implications for better practical application and environmental risk assessment of zoxamide enantiomers.