Molecular design of environment-friendly amide herbicide substitutes with high efficacy, low phytotoxicity and medication safety

Abstract

The primary goal of this investigation was to formulate an ecologically sustainable alternative to amide herbicides (AHs) characterized by robust herbicidal effectiveness, minimal corn phytotoxicity, and commendable pharmaceutical safety. We employed comparative molecular similarity index analysis (CoMSIA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) model, which systematically outlined parameters such as herbicidal effectiveness, corn phytotoxicity, and AHs biodegradability. Subsequently, after thorough evaluation, we carefully selected a group of fourteen stable AH-substitute compounds known for their safety and environmental compatibility, considering aspects like pharmacokinetics, toxicokinetics, functional properties, and environmental friendliness. This resulted in a significant increase in herbicidal effectiveness, ranging from 21.64% to 34.07%, alongside a decrease in corn phytotoxicity within the range of 12.19–20.87%. Furthermore, we achieved an improvement in biodegradability, measured within the spectrum of 4.92–9.40%. Importantly, these changes also correlated with the reduction of hepatotoxicity, mutagenicity, and cutaneous health risks. Finally, we delved into the mechanisms underlying the improved herbicidal effectiveness, reduced corn phytotoxicity, and enhanced biodegradability of AHs substitutes through molecular docking and analysis of amino acid interactions. The investigation concluded that non-covalent forces governing the interaction between AHs substitutes and receptor proteins are crucial in determining herbicidal effectiveness, corn phytotoxicity, and biodegradability. Specifically, Van der Waals and electrostatic forces emerged as key factors governing the binding affinities of AH molecules with receptor proteins, both before and after modification. In summary, this study introduces innovative approaches in the field of agricultural chemical weeding technology and provides a theoretical framework for the environmentally responsible management of AHs herbicides.