Synthesis, antimicrobial activities, docking studies and computational calculations of new bis-1,4-phenylene -1<i>H</i>-1,2,3-triazole derivatives utilized ultrasonic energy

Abstract

In this elucidation, we studied the utility of condensation reaction between 1,4-phenylenediamine (<b>1</b>) with acetyl acetone (<b>2</b>) with hydrazine hydrate utilized ultrasonic energy in one step reaction to afford the corresponding 1,1'-(1,4-phenylenebis (5-methyl-1<i>H</i>-1,2,3-triazole-1,4-diyl))bis(ethan-1-one) (<b>4</b>) in excellent yield. The ethanol solution of bis triazole (<b>4)</b> and different aldehyde derivatives were sonicated at 75 °C for 2 h to afford chalcone derivatives <b>5a-d</b> which were confirmed via spectral data such as FTIR, ¹HNMR, ¹³CNMR and mass spectra. Moreover, the intermolecular cyclization of chalcone <b>(5a</b>) with NH₂NH₂ in sodium hydroxide solution to give the corresponding 4,5-dihydro-1<i>H</i>-pyrazol-5-yl)-1<i>H</i>-indole <b>(6)</b> using ultrasonic energy for 4 h, while the Michael addition of chalcones <b>(5a</b>) and <b>(5 b)</b> with thiourea in basic condition to afford the corresponding pyrimidine-2-thiol derivatives <b>(7)</b> and <b>(9)</b>. Treatment of compound <b>(7</b>) with NH₂NH₂ to afford 1,4-bis(4-(2-hydrazineyl-6-(1<i>H</i>-indol-3-yl)pyrimidin-4-yl) derivatives <b>(8</b>). The synthesized compounds were screened against various microbial strains and displayed excellent antimicrobial potential. Additionally, the docking studies of these nine compounds were carried out with (<b>PDB ID</b>:3t88), (<b>PDB ID</b>:2wje), (<b>PDB ID</b>:4ynt) and (<b>PDB ID</b>:1tgh) which were attached with different amino acids with shortage bond length, and it was noticed that <b>PMTS₁, PMTS₂</b> and <b>PMTS₃</b> were the most stable compounds with the lowest energy affinity which is compatible with biological study. Furthermore, the theoretical investigation of bis-triazole compounds were optimized via DFT/B3LYP/6-31G(d) level which showed the hyperconjugation of nitrogen atoms and elucidated their physical parameters and NBO charges and confirmed their stability and biological activity.Communicated by Ramaswamy H. Sarma.