In the present study, an eco-friendly and efficient microwave-assisted synthesis of the (E)-4-((3,4-difluorobenzylidene)amino)-2,4-dihydro-5-methyl-3H-1,2,4-triazole-3-thione Schiff base ligand was described. XRD-single crystal analysis reflected the molecule occurs in an exo-thione tautomeric form in solid state. Therefore, gaseous-phase prototropic thione thiol tautomerism occurrence probability via single-proton intramigration and push/pull protons self-assemble double proton transfer exchange was DFT-computed. The newly designed thione-tautomer was well-characterized by MS, FT-IR, CHN-EA, 19F, 1H, 13C NMR, and XRD analysis. High degree of matching was recorded by comparing the experiment XRD exo-thione-tautomer structure parameters by their relatives DFT-optimized parameters. Moreover, the computed MEP and HSA surface interactions were compared to H-bonds and π-π stack interactions obtained by XRD-packing analyses. Docking studies reflected the compound as DNA strong hydrophobic pocket binder. © 2018 Elsevier B.V.