X-ray and theoretical investigation of ()-3-(adamantan-1-yl)-1-(phenyl or 3-chlorophenyl)--(4-bromobenzyl)isothioureas: an exploration involving weak non-covalent interactions, chemotherapeutic activities and QM/MM binding energy.

A detailed exploration of crystal packing of two adamantane-isothiourea hybrid derivatives along with a known closely related structure has been performed to delineate the effect of halogen substituents and the role of weak intermolecular interactions in their supramolecular architectures. The adamantane-isothiourea hybrid derivatives used in the present study are ()-3-(Adamantan-1-yl)--(4-bromobenzyl)-1-phenylisothiourea (), CHBrNS and ()-3-(Adamantan-1-yl)--(4-bromobenzyl)-1-(3-chlorophenyl)isothiourea (), CHBrClNS, characterized by X-ray crystallography. The X-ray structures revealed that the molecular conformation of and are different and stabilized by intramolecular C-H···N interactions. In addition, a short intramolecular H···H contact is formed in . The Hirshfeld surface analysis was used to delineate the nature of different intermolecular interactions and their contributions toward crystal packing. The quantitative analysis of strengths of molecular dimers existed in and has been performed using the PIXEL method. The electrostatic potential map clearly revealed nature and strength of σ-holes at Br and Cl atoms. The topological analysis was used to characterize the nature and the strength of various intermolecular interactions including the type I Br···Br contact. Interestingly, all the H-H bonding observed in and show closed-shell in nature. Further, an antimicrobial activity studies suggest that the title compounds exhibited potent antibacterial activity against all the tested Gram-positive bacterial strains and Gram-negative . Compound showed marked anti-proliferative activity against MCF-7 and HeLa cell lines.Communicated by Ramaswamy H. Sarma.