Tautomerism of herbicides metribuzin, diclosulam and clethodim: evaluation of different parameters for structure assignation

Abstract

Pesticides are widely used in agriculture, and they can cause serious damage to human health and to the environment. In this work, three herbicides are studied regarding possible tautomeric equilibria: clethodim, diclosulam and metribuzin. Tautomerism is a key reaction that is directly related to action, disposition and toxicity of herbicides, and here lies the importance of this study. The specific aim of this work is to compare classical parameters (MAE and R2) with DP4+ method as a tool for obtaining relevant information about tautomeric equilibria in the three compounds, contrasting experimental NMR data with theoretical calculations carried out using DFT methods.1H and 13C NMR spectra of the three herbicides were recorded in DMSO‑d6. Additionally, HSQC and COSY spectra were obtained for clethodim. Theoretical calculations were carried out in order to obtain optimized geometries in vacuum (using B3LYP method at 6–31G(d,p) level of theory); and chemical shifts of nuclei corresponding to all possible tautomers of each herbicide were obtained by means of B3LYP-GIAO method using 6–311+G(2d,p) basis set.In the three cases, classical comparison parameters MAE and R2 fail in the assignation of tautomers since they gave doubtful or even inconsistent results. In the case of metribuzin, MAE values obtained from 1H and 13C point towards different structures. R2 and MAE values obtained from 1H and 13C are very close when comparing the two tautomers, and the assignation is not certain. The case of clethodim is more confusing, since the R2 and MAE values suggest that all signals correspond to the same structure. DP4+ method, on the other hand, gave more reliable results (within the set of proposed structures). It is important to remark that DP4+ method has been used before for tautomer assignation in only one case (to the best of our knowledge), and it has also proven successful in this context of use.We concluded that metribuzin and diclosulam exist in solution in one major tautomeric form (aminotriazinone and sulfonamide, respectively), while two tautomers of similar energy (E- and Z-ketoenolimine complexed with DMSO) are proposed for clethodim.