(E)-1-(Substituted Benzylidene)-4-(3-Isopropylphenyl)Thiosemicarbazone Derivatives: Experimental And Theoretical Studies

Thiosemicarbazone derivatives attract the attention of researchers due to their typical structural characteristics and wide application value.The inherent tridentate coordination framework(=NNS―)of thiosemicarbazone derivatives easily chelates with metal-ions to form complexes,which can further improve the anticancer,antibacterial,antiviral,antifungal,antimalarial and other biological activities by preventing the formation of hydroxides and increasing the affinity of cell membrane.In this paper,the 10 novel(E)-1-(substituted benzylidene)-4-(3-isopropylphenyl)thiosemicarbazone derivatives were synthesized,and the structures were characterized by high resolution mass spectrometry(HR-MS),elemental analysis(EA),infrared spectroscopy(FT-IR)and nuclear magnetic resonance(NMR).Besides,the crystal data of(E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone(compound 1),(E)-1-(4-methylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone(compound 4)and(E)-1-(3-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone(compound 7)was measured by X-ray single crystal diffraction technique.Taking compounds 1 and 7 as examples,Hirshfeld surface was introduced to analyze the intermolecular hydrogen bonds and contributions of short contacts to crystal packing.In the case of compound 3,the geometric configuration was optimized using B3LYP/6-31+G(d,p)basis set,and the most stable configuration obtained was used as initial configuration for the subsequent quantum chemical calculations.What’s more,the structural characteristics and electronic properties were studied by molecular electrostatic potential(ESP),frontier molecular orbital(FMO),UV-Visible absorption spectroscopy(UV-Vis)and topological analysis,which laid the solid theoretical foundation for further excavating the biological activity of thiosemicarbazone derivatives.The antifungal and antioxidant activities of the 10 synthesized compounds were tested to study the influence of the types and positions of the substituents on biological activity,and results indicate that compound 6 has the obvious inhibitory activity on 4 tested pathogens and the replacement of fluorine at benzene ring para obviously promotes the antifungal activity.Meanwhile,molecular docking technology was used to simulate the docking mode of 10 synthesized compounds and the antifungal receptor protein 1NMT.In vitro antioxidant experiment finds that compound 3 possesses a good antioxidant potential.Finally,the drug-likeness characteristic and pharmacokinetic properties of 10 synthesized compounds were evaluated.