Energetic features of H-bonded and antiparallel π-stacked supramolecular assemblies in pyrazolones: Experimental, computational and biological analyses

Abstract

The work presented herein outlines a straightforward synthetic route to produce a series of pyrazolone compounds, which are significant in both coordination chemistry and pharmaceutical research. These heterocyclic compounds were thoroughly characterized using FTIR, 1H and 13C NMR spectroscopy, and their molecular structures were conclusively determined through X-ray crystallography. The resulting supramolecular architectures feature a variety of noncovalent interactions, including conventional NH…O and CH…O hydrogen bonds, CH…halogen contacts, CH…N interactions, and offset π-π stacking. Density Functional Theory (DFT) calculations, alongside Molecular Electrostatic Potential (MEP) surface analysis and Quantum Theory of Atoms in Molecules (QTAIM)/Non-Covalent Interaction (NCI) plot methodologies, were employed to probe these interactions further. This analysis highlighted the significance of both CH…O and NH…O hydrogen bonds and revealed the critical role of antiparallel π-stacking interactions, particularly within chlorophenyl and benzonitrile substituted pyrazolones, underscoring their stabilizing effects on the molecular structure. Biological assessment against urease enzyme unveiled compound 3a as the lead inhibitor with an IC50 value of 0.71 ± 0.09 μM and 31-folds strong inhibition than thiourea, thus making pyrazolone heterocycles as potential drug candidates.