Design, Synthesis, Antimicrobial Evaluation, Molecular Docking, and Computational Studies of New 1,2,4-Triazolo[4,3-a]pyrimidin-5(1 H)-one Derivatives

This study reports the synthesis and comprehensive characterization of a new series of 1,2,4-triazolo[4,3-a] pyrimidin-5-(1H)-one derivatives. These compounds were synthesized from 2-hydrazinopyrimidines via cyclization reactions. Density Functional Theory (DFT) calculations revealed the molecular structures, stability, and electronic properties of the derivatives. Computational studies revealed that the compounds exhibited planar conformations, though the triazole rings were found to be non-coplanar with the pyrimidine ring. Substituents like methyl, amino, and propyl groups influenced bond lengths, dihedral angles, and electronic properties. Binding energies confirmed molecular stability, while IR spectra supported dynamical stability. UV-Vis’s absorption spectra matched experimental data, showing maxima in the 250–400 nm range, with redshifts attributed to electron-donating substituents. Density of State (DOS) and HOMO/LUMO analyses indicated strong orbital interactions and electron delocalization. Molecular docking studies suggested favorable binding with the DNA gyrase receptor, indicating potential antimicrobial activity against both Gram-positive and Gram-negative bacteria. This study provides valuable insights into the synthesis, structural, electronic, and antimicrobial properties of 1,2,4-triazolo[4,3-a] pyrimidin-5-(1H)-one derivatives, highlighting their potential applications in medicinal chemistry and materials science.