Mechanism analysis and improved molecular modification: Design of high efficiency and environmentally friendly...

The adverse effects of triazole fungicides (TFs) on the soil and the environmental damage caused by their residues have attracted the attention of the international community. To effectively prevent and control the above problems, this paper designed 72 substitutes of TFs with significantly better molecular functionality (>40%) using Paclobutrazol (PBZ) as the template molecule. Then, the comprehensive scores for environmental effects calculated after normalization by "extreme value method-entropy weight method-weighted average method" was the dependent variable, the structural parameters of TFs molecules was the independent variable (PBZ-214 was the template molecule) to construct the 3D-QSAR model of integrated environmental effects of TFs with high degradability, low bioenrichment, low endocrine disruption effects, and low hepatotoxicity and designed 46 substitutes of TFs with significantly better comprehensive environmental effects (>20%). After confirming the above effects of TFs and assessing human health risk and the universality of biodegradation and endocrine disruption, we screened PBZ-319-175 as the eco-friendly substitute of TF, which had high efficiency (improved functionality) and better environmental effects than those of the target molecule by 51.63% and 36.09%, respectively. Finally, the results of the molecular docking analysis showed that non-bonding interactions (hydrogen bonding, electrostatic, or polar force) predominantly affected the association between PBZ-319-175 and its biodegradable protein, and the hydrophobic effect of the amino acids distributed around PBZ-319-175 played a significant role. Additionally, we determined the microbial degradation path of PBZ-319-175 and found that the steric hindrance of the substituent group after molecular modification promoted its biodegradability. In this study, we enhanced molecular functionality twice and also reduce the major damage of TFs to the environment by performing iterative modifications. This paper provided theoretical support for the development and application of high-performance, eco-friendly substitutes of TFs.