Effect of Herbicide Terbutryn on the DNA Base Pairs: Design of New Herbicide with the Minimum Toxicity

Terbutryn [2-(t-butylamino)-4-(ethylamino)-6-(methylthio)-s-triazine] (TB) is a widely used pre-emergence and post-emergence s-triazine carcinogen herbicide in agriculture as a control agent for most grasses and many annual broadleaf weeds in cereal and legume fields, and also under fruit trees. Current effort of this research is to investigate how the structure and dynamics of DNA-binding is affected by TB. Molecular modeling on the complex formed between TB and DNA has shown that this complex is indeed fully capable of participating in the formation of a stable intercalation site. Therefore, molecular geometries of TB and the canonical Watson-Crick base pairs (adenine (A) forms a base pair with thymine (T), as does guanine (G) with cytosine (C) in DNA) were optimized using DFT/B3LYP method. Properties of the isolated intercalator and its stacking interactions with A = T and G ≡C nucleic acid base pairs were studied using DFTB method, an approximate version of the DFT method, which was extended to cover London dispersion energy. B3LYP/6-31G* stabilization energies of intercalator···base pair complexes were obtained to be -20.31 kcal/mol and -36.23 kcal/mol for A = T··· TB and G ≡ C··· TB, respectively. At the end, It was concluded that, dispersion energy and electrostatic interaction contribute to the stability of intercalator··· DNA base pair complexes.