Structure–activity relationship study of substituted 1,2,3-thiadiazoles as novel nitrification inhibitors for agriculture

Nitrification inhibitors are used in agricultural soils to maintain ammonium (NH₄⁺) available for crops for longer periods while reducing leaching of nitrate (NO₃^-) and emission of the potent greenhouse gas nitrous oxide (N₂O). Unfortunately, and for reasons not well understood, the current commercial inhibitors have shown inconsistencies in their performance across various agroecosystems, underscoring the need for the development of new nitrification inhibitor compounds to increase agriculture's environmental sustainability. In this work, we have performed structure-activity relationship (SAR) studies to explore the potential of 12 mono- and disubstituted 1,2,3-thiadiazoles as nitrification inhibitors through laboratory soil incubations. 1,2,3-Thiadiazoles substituted with one or two methyl groups as well as those with a fused cyclopentyl ring showed the most promising inhibitory activities, which can outperform the commercial nitrification inhibitor 3,4-dimethylpyrazole (DMP). Larger alkyl substituents as well as substituents with polar functional groups showed poorer or no inhibitory activity. These data align with our previous findings for substituted 1,2,3-triazoles that short, non-polar alkyl substituents on the heteroaromatic framework are beneficial for nitrification inhibitory properties.