Hydrogen bonding, halogen bonding and C - H ... π interactions governing the supramolecular architecture of 1-(4-(4-bromophenyl) piperazin-1-yl)-2-chloroethan-1-one: Insights from X-ray crystallography, DFT calculations and urease inhibitory assessment

The use of organic ligands for the generation of supramolecular architectures exhibiting interesting structural properties in crystal engineering have garnered significant attention. In this context, the current work highlights the use of 1-(4-(4-bromophenyl)piperazin-1-yl)-2-chloroethan-1-one (3) 3 ) as a valuable synthon for evaluating the conspicuous role of several types of noncovalent interactions governing the formation of supramolecular assemblies. Compound 3 was successfully synthesized in good yield using a facile two-step approach and characterized through spectroscopic and X-ray crystallographic methods. Noncovalent interactions including C-H... O, C-H...Cl, C-H...pi as well as C-Br...Cl halogen bonds were found as the key contacts in the crystal packing of compound 3 . DFT calculations were employed to identify and assess the impact of the C-Br...Cl halogen bond, utilizing MEP, QTAIM, and NBO analyses. These studies confirmed that the Br atom acts as the halogen bond donor and the Cl atom as the halogen bond acceptor. Assessment of urease inhibitory efficacy revealed that the tested compound exhibits a 16-folds superior inhibition than thiourea. Computational modeling analysis augmented the in vitro results by exhibiting numerous favorable binding interactions between compound 3 and active site residues such as TYR32, LYS709, PHE712, ASP730, VAL744 and MET746. The pharmacokinetic evaluation classified the investigated piperazine derivative into a druggable compound.