Probing the hybridized triazole-chalcones: an in-depth investigations of molecular structure journey towards antibacterial potential against DNA gyrase.

The present study delves into the comprehensive structural investigations of the six Chalcone derivatives (4A-F), each featuring the 1, 2, 3 triazole linkages. The work commences with the synthesis by employing a multifaceted approach to unravel its molecular properties and potential biological significance. Single crystal X-ray diffraction technique was used to determine the precise 3D structure of the grown single crystals of 4D and 4F. The crystal structure exhibited significant investigations on intermolecular interactions, particularly hydrogen bonding, π-π stacking, Van der Waals forces and other intra-intermolecular interactions contributing to the molecular assembly. Density Functional Theory (DFT) was employed using the B3LYP functional and 6-311++ G (d, p) basis set to explore compound's electronic structure and physicochemical properties. Quantum theory of atoms in molecule (QTAIM) and non-covalent interactions (NCI) analysis provided insights into the topology of the compounds. Further the biological assessments were performed to know the antimicrobial properties of the compounds against both gram-negative and gram-positive bacteria. The research also culminated the evaluation of the drug-likeness of the compounds, drawing upon ADME-T predictions. Further, in silico molecular docking and dynamics simulation analysis were conducted to anticipate the most favorable binding configuration of the derivatives within the active site cavity of the Type II topoisomerase DNA gyrase receptors. In vitro antimicrobial study was also performed and it demonstrated notable results. Overall, this extensive study offers a deep study into the structural intricacies of these compounds, providing insights for chemical and biological evaluations, particularly in the context of bacterial enzyme inhibition.