Objective：To explore benzothiazoles’ structures and spectral properties and their analogues using the density functional theory method. Methods：The geometric and electronic structures, UV-Vis absorption spectra, infrared vibrational spectra, Raman spectra, fluorescence spectra, and vibrational circular dichroism of benzothiazole drugs riluzole, ethoxzolamide, frentizole, zopolrestat and four analogues were calculated and analyzed using density functional theory at the X3LYP/6-311+ G (d, p) level. The possible reaction sites were quantified and visualized using conceptual density functional theory. Results：The four drugs had the same pharmacophoric structure. The calculated values of riluzole and frentizole molecules’ geometric data were nearly consistent with the experimental values. The four analogues (4 minimal inhibitory concentration compounds, codes 43, 70, 71, 78) had a similar spatial distribution of planar rings, and the same chemical bonds C-Cl and C-F in the MS43 were the shortest. The electrostatic potential maximum sites in riluzole, ethoxzolamide, and frentizole were mainly distributed near the amine group, the carboxyl group in zopolrestat, and around the benzene ring four analogues and werevulnerable to nucleophilic reagent attacks. The sites near the thiazole ring of riluzole, sulfonyl group in ethoxzolamide and ketone group in frentizole and zopolrestat, and the triazole ring of the four analogues wereapt to electrophilic reagent reaction. Riluzole and MS 43 had the greatest red-shift in the UV wavelength of the benzene ring. The molecules substituted by F atoms in the benzene ring in the four analogues all produced a strong absorption peak near 1 096 cm-1 in the infrared spectra, with a change in order MS 78> MS 70> MS 43> MS 71. The fluorescence spectrum π → π* transition was from benzothiazole ring to benzene ring and triazole ring containing halogen group. And the different positive and negative Cotton effects were shown in the vibrational dichromatic spectrum. The additional positive and negative Cotton effects in vibrational circular dichroism spectra observed. Conclusion：The calculation and analysis of spectral characteristics of riluzole, esolazolamide, fumentizole, zolpostatat and four analogs provids a basis for the identification of authenticity, impurity control and other spectral determination.
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