Open AccessCrystallographic and Theoretical Exploration of Weak Hydrogen Bonds in Arylmethyl N′-(adamantan-1-yl)piperidine-1-carbothioimidates and Molecular Docking Analysis
Author(s) -
Aamal A. Al-Mutairi,
Kowsalya Alagappan,
Olivier Blacque,
Monirah A. Al-Alshaikh,
Ali A. El-Emam,
M. Judith Percino,
Subbiah Thamotharan
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.1c03559
Subject(s) - piperidine , morpholine , chemistry , intermolecular force , hydrogen bond , molecule , crystal structure , docking (animal) , cyclohexane conformation , crystallography , stereochemistry , medicinal chemistry , organic chemistry , medicine , nursing
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/NO 2 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···S, C-H···O, and O(lp)···C(π) interactions, whereas compound 2 stabilizes with C-H···N, C-H···Br, and C-H···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.