4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol as potent antimicrobial agent: Synthesis, X-ray, antimicrobial activity and computational studies

Abstract

In this work, 1,2,4-triazole derivative derived from Isoniazid namely, 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol (APTT) was synthesized and fully characterized by FT-IR, 1H NMR, 13C NMR, HRMS-ESI, and single crystal X-ray diffraction. The optimized structures of monomer, dimer and tetramer of APTT with the hybrid B3LYP/6-311++G** method explain the inter and intra-molecular interactions observed experimentally by X-ray diffraction. The presence of tetramer justify the strong IR bands observed in the 2400 and 1800 cm-1 region. The IR spectrum was completely assigned and the scaled force constants reported by using the scaled quantum mechanical force field (SQMFF) approach and the Molvib program. Good correlations between experimental and predicted NMR and UV-Vis spectra are obtained. Both NBO and AIM calculations reveal the inter and intra-molecular interactions and the low stability of APTT in solution while the gap values suggest its low reactivity in the same medium. The different studies reveal the important role of intra and inter-molecular interactions in the stability and reactivity of APTT in the two media. Also, antimicrobial activity of APTT was evaluated against common bacteria and fungi as S. aureus, S. pyrogenes, E. faecalis, V. parahaemolyticus, P. aeruginosa, S. enteritidis, S. cerevisiae, C. albicans, C. tropicalis, C. glabrata, and C. parasilosis. The antimicrobial activity results showed that APTT exhibited both bactericidal and fungicidal activity against all the microbial strains tested. These two effects underline the versatility of the title compound in combating a broad spectrum of microbial infections.