Functionalized Thiadiazole: Synthesis, insecticidal activity, molecular docking and DFT studies of some new 5-substituted 1,2,4-Thiadiazoles based on Norfloxacin

Abstract

Through plant protection, we hope to contribute to the growth of cotton production—the most significant non-food agricultural commodity. The use of safe substitutes for pesticides has become essential because of a number of grave problems related to their use. Consequently, families of novel environmentally benign Norfloxacin series with insecticidal efficacy based on 5-Substituted 1,2,4-thiadiazoles were identified. The Target synthesized compounds were confirmed by elemental and modern spectroscopic analyses (such as IR, UV, ¹H NMR and ¹³C NMR). The toxicological activity of this compounds were checked towards nymphs and adults of Aphis gossypii which the most affected compound 7 had an LC₅₀ of 0.907 mg/L, while the LC₅₀ of commercial thiacloprid was 0.255 mg/L. Due to the presence of carboxalic acid and fluorophenyl groups in their chemical composition, component 7 may be especially effective. Density Functional Theory (DFT) analysis of the synthesized compounds using the B3LYP hybrid functional and the 6-311G(d,p) basis set provided valuable insights into their electronic properties and chemical reactivity. Frontier Molecular Orbital (FMO) analysis revealed that compound 7, with the smallest HOMO-LUMO gap (ΔE = 2.94 eV), exhibited the highest reactivity, suggesting its potential for significant biological interactions. Moreover, molecular docking studies against the 4EY4 hydrolase enzyme indicated strong binding affinities for compounds 3, 5, 7 and 8 with docking scores surpassing the standard Thiacloprid, confirming their enhanced bioactivity. These results, when correlated with quantum chemical parameters and biological assays, highlight the promising therapeutic potential of the new compounds, especially compound 7.