Crystallographic and Theoretical Exploration of Weak Hydrogen Bonds in Arylmethyl N'-(adamantan-1-yl)piperidine-1-carbothioimidates and Molecular Docking Analysis

Crystal structures of two potential chemotherapeutic agents, namely 4-nitrobenzyl N'-(adamantan-1-yl)piperidine-1-carbothioimidate 1 and 4-bromobenzyl N'-(adamantan-1-yl)piperidine-1-carbothioimidate 2, have been analyzed in detail. X-ray analysis reveals that the molecular conformations of these compounds are strikingly different. These two structures are compared with two of their closely related structures. In the related structures, morpholine replaces piperidine. Based on the Hirshfeld surface analysis and two-dimensional (2D) fingerprint plots, we describe the effects of piperidine/morpholine and Br/NO2 groups on the intermolecular interactions. An analysis of the CLP-PIXEL energy provides insight into the energetics of the dimers observed in the title compounds and their related structures. Compound 1 stabilizes with bifurcated C-H center dot center dot center dot S, C-H center dot center dot center dot O, and O(lp)center dot center dot center dot C(pi) interactions, whereas compound 2 stabilizes with C-H center dot center dot center dot N, C-H center dot center dot center dot Br, and C-H center dot center dot center dot C interactions. The energy frameworks for the crystal structures of the title compounds reveal differences. The atoms-in-molecules (AIM) analysis was performed to confirm the intermolecular interactions found in the crystal structures of 1 and 2. Additionally, docking analysis suggests that the title compounds bind at the active site of human sphingosine kinase 1, a well-known cancer target.