Impact of Chlorine Substitution on the Interaction Between Amide Herbicides and Alkaline Phosphatase: Insights into Molecular Mechanisms and Structure-Activity Relationships.

Abstract

Amide herbicides (AHs), commonly applied in agriculture, are now known to inhibit the activity of alkaline phosphatase (AKP), subsequently disturbing the soil microbial community and spurring significant shifts in soil nutrient dynamics. The complex mechanisms governing the interaction between AHs and AKP, along with the impact of halogen substituents in AHs on AKP function and this study sets out to investigate these interactions. By integrating computational docking techniques with Spearman correlation analysis and focusing on seven typical AHs, we probed the mechanisms of the AHs-AKP complex and aimed to clarify the structure-activity relationship between these herbicides and AKP. Our findings disclose that within the AKP-AHs complex, the proportion of neutral amino acids peaked at 48.41%. The chief interaction patterns between AKP and AHs hinged on hydrogen bonding and hydrophobic interactions. Among the AHs, butachlor exhibited the largest binding area (BA ≈ 452.61 Ų), implying stronger binding than its counterparts. In contrast, propanil manifested the maximum absolute value of binding energy (|BE|) at 2.94 kJ/mol, indicating that it may possess stronger binding characteristics despite the larger BA of butachlor. This discrepancy may be attributed to the chlorine atom content of propanil relative to the other AHs, which enhances its interaction with AKP through increased hydrophobicity and specific interactions. Moreover, our analysis reveals a negative correlation between the molecular weight (MW) of the AHs and their corresponding |BE| values, signifying that as MW rises, the binding energy of the AHs-AKP interaction declines. This suggests a potential inverse relationship. In sum, these findings provide critical technological insights and foundational theory for understanding the harmful impacts of AHs via the halogen effect (Cl) on soil enzyme inhibition, with implications for health risk management and regulation. These insights are crucial for understanding the environmental impact of AHs and informing risk management strategies.