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


Al-Mutairi, Aamal A; Alagappan, Kowsalya; Blacque, Olivier; Al-Alshaikh, Monirah A; El-Emam, Ali A; Percino, M Judith; Thamotharan, Subbiah (2021). Crystallographic and Theoretical Exploration of Weak Hydrogen Bonds in Arylmethyl N′-(adamantan-1-yl)piperidine-1-carbothioimidates and Molecular Docking Analysis. ACS Omega, 6(41):27026-27037.

Abstract

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···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.

Abstract

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···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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > General Chemistry
Physical Sciences > General Chemical Engineering
Uncontrolled Keywords:General Chemical Engineering, General Chemistry
Language:English
Date:19 October 2021
Deposited On:13 Jan 2022 14:21
Last Modified:14 Jan 2022 21:01
Publisher:American Chemical Society (ACS)
ISSN:2470-1343
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1021/acsomega.1c03559
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)