Bromo substituted aroylhydrazones: Synthesis, crystal structures, Hirshfeld surface analysis, 3D energy frameworks, DNA/BSA binding, and antimicrobial activity

Abstract

Two bromo substituted aroylhydrazones such as 2-benzoylpyridine-4-bromobenzhydrazone (HBpB) and di-2-pyridyl ketone-4-bromobenzhydrazone (HDpB) were synthesized. The synthesized compounds have been characterized physicochemically using CHNS analysis, FT-IR, UV-vis absorption, 1H NMR and high resolution-mass spectra and the structures have been confirmed with single crystal X-ray diffraction technique. HBpB got crystallized in the monoclinic P21/c space group and the HDpB in the triclinic P1¯ space group. The supramolecular interactions present in the crystal system were studied with Hirshfeld surface (HS) analysis. The energy frameworks have been built by using different intermolecular interaction energies in order to study the stability of the molecule and determine the dominant energy type. The average interaction energy values for compounds HBpB and HDpB are found to be -280.4 and -327.2 kJ mol−1, respectively. Further, the nature of frontier orbitals and the stability of the compounds in the gas phase were theoretically analyzed, and the electrostatic potential surface diagram were plotted on optimized geometries. The binding potentials of HBpB and HDpB with DNA and BSA protein were investigated using spectroscopic, electrochemical, and in silico molecular docking methods. The results showed that HBpB has a higher binding affinity with both DNA and BSA compared to HDpB. Both HBpB and HDpB interact with DNA through a minor groove mode, while their binding to BSA involves mainly hydrophobic type. The ADMET analysis of compounds yielded favorable results for their potential use in pharmacological applications. When assessing the antibacterial capabilities of the tested samples, both the compounds showed good antimicrobial activities towards Klebsiella pneumonia, Bacillus Subtilis, Pseudomonas aeruginosa and Escherichia Coli.