Molecular Determinants of Efficacy: A Mechanistic Overview of Fertilizer Synergists

With the increasing demand for sustainable agriculture and efficient nitrogen fertilizer utilization, fertilizer synergists, including urease inhibitors, nitrification inhibitors, and biostimulants, have received a growing amount of attention. However, their mechanisms of action are often examined in isolation, and a unified structure-activity relationship (SAR) framework linking molecular structure to efficacy is still lacking. This review provides a mechanistic overview of fertilizer synergists from a molecular perspective, integrating SARs across these three classes. For urease and nitrification inhibitors, molecular features governing enzyme recognition and binding predominantly determine the inhibitory efficacy. By contrast, biostimulants exhibit more complex and multilayered SARs, in which molecular structure not only enhances nutrient utilization but also modulates plant signaling pathways, thereby promoting stress tolerance and plant growth. Finally, this review provides structure-guided insights and design strategies to support the development of novel fertilizer synergists with improved efficiency, multifunctionality, and environmental compatibility.