Theoretical investigations of two adamantane derivatives

A combined X-ray, DFT, QTAIM analysis and molecular docking

Lamya H. Al-Wahaibi, Subramaniam Sujay, Gangadharan Ganesh Muthu, Ali A. El-Emam, Natarajan S. Venkataramanan, Fatmah A.M. Al-Omary, Hazem A. Ghabbour, Judith Percino, Subbiah Thamotharan

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

A detailed structural analysis of two adamantane derivatives namely, ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(phenyl)isothioureido]acetate I and ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(4-fluorophenyl)isothioureido]acetate II is carried out to understand the effect of fluorine substitution. The introduction of fluorine atom alters the crystal packing and is completely different from its parent compound. The fluorine substitution drastically reduced the intermolecular H⋯H contacts and this reduction is compensated by intermolecular F⋯H and F⋯F contacts. The relative contributions of various intermolecular contacts present in these structures were quantified using Hirshfeld surface analysis. Energetically significant molecular pairs were identified from the crystal structures of these compounds using PIXEL method. The structures of I and II are optimized in gas and solvent phases using the B3LYP-D3/6-311++G(d,p) level of theory. The quantum theory of atoms-in-molecules (QTAIM) analysis was carried out to estimate the strengths of various intermolecular contacts present in these molecular dimers. The results suggest that the H–H bonding take part in the stabilization of crystal structures. The experimental and theoretical UV–Vis results show the variations in HOMO and LUMO energy levels. In silico docking analysis indicates that both compounds I and II may exhibit inhibitory activity against 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD1).

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalJournal of Molecular Structure
Volume1159
DOIs
Publication statusPublished - 5 May 2018

Fingerprint

Adamantane
Design for testability
Fluorine
Quantum theory
Derivatives
X rays
Atoms
Molecules
Substitution reactions
Crystal structure
11-beta-Hydroxysteroid Dehydrogenases
Surface analysis
Structural analysis
Dimers
Electron energy levels
Acetates
Stabilization
Gases
Crystals

Keywords

  • 11-β-HSD1
  • Adamantane
  • Chair conformation
  • H–H bonding
  • PIXEL
  • QTAIM

Cite this

Al-Wahaibi, Lamya H. ; Sujay, Subramaniam ; Muthu, Gangadharan Ganesh ; El-Emam, Ali A. ; Venkataramanan, Natarajan S. ; Al-Omary, Fatmah A.M. ; Ghabbour, Hazem A. ; Percino, Judith ; Thamotharan, Subbiah. / Theoretical investigations of two adamantane derivatives : A combined X-ray, DFT, QTAIM analysis and molecular docking. In: Journal of Molecular Structure. 2018 ; Vol. 1159. pp. 233-245.
@article{d541c55f7f9f4711ac78c8f84c3e42ba,
title = "Theoretical investigations of two adamantane derivatives: A combined X-ray, DFT, QTAIM analysis and molecular docking",
abstract = "A detailed structural analysis of two adamantane derivatives namely, ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(phenyl)isothioureido]acetate I and ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(4-fluorophenyl)isothioureido]acetate II is carried out to understand the effect of fluorine substitution. The introduction of fluorine atom alters the crystal packing and is completely different from its parent compound. The fluorine substitution drastically reduced the intermolecular H⋯H contacts and this reduction is compensated by intermolecular F⋯H and F⋯F contacts. The relative contributions of various intermolecular contacts present in these structures were quantified using Hirshfeld surface analysis. Energetically significant molecular pairs were identified from the crystal structures of these compounds using PIXEL method. The structures of I and II are optimized in gas and solvent phases using the B3LYP-D3/6-311++G(d,p) level of theory. The quantum theory of atoms-in-molecules (QTAIM) analysis was carried out to estimate the strengths of various intermolecular contacts present in these molecular dimers. The results suggest that the H–H bonding take part in the stabilization of crystal structures. The experimental and theoretical UV–Vis results show the variations in HOMO and LUMO energy levels. In silico docking analysis indicates that both compounds I and II may exhibit inhibitory activity against 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD1).",
keywords = "11-β-HSD1, Adamantane, Chair conformation, H–H bonding, PIXEL, QTAIM",
author = "Al-Wahaibi, {Lamya H.} and Subramaniam Sujay and Muthu, {Gangadharan Ganesh} and El-Emam, {Ali A.} and Venkataramanan, {Natarajan S.} and Al-Omary, {Fatmah A.M.} and Ghabbour, {Hazem A.} and Judith Percino and Subbiah Thamotharan",
year = "2018",
month = "5",
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doi = "10.1016/j.molstruc.2018.01.064",
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Al-Wahaibi, LH, Sujay, S, Muthu, GG, El-Emam, AA, Venkataramanan, NS, Al-Omary, FAM, Ghabbour, HA, Percino, J & Thamotharan, S 2018, 'Theoretical investigations of two adamantane derivatives: A combined X-ray, DFT, QTAIM analysis and molecular docking', Journal of Molecular Structure, vol. 1159, pp. 233-245. https://doi.org/10.1016/j.molstruc.2018.01.064

Theoretical investigations of two adamantane derivatives : A combined X-ray, DFT, QTAIM analysis and molecular docking. / Al-Wahaibi, Lamya H.; Sujay, Subramaniam; Muthu, Gangadharan Ganesh; El-Emam, Ali A.; Venkataramanan, Natarajan S.; Al-Omary, Fatmah A.M.; Ghabbour, Hazem A.; Percino, Judith; Thamotharan, Subbiah.

In: Journal of Molecular Structure, Vol. 1159, 05.05.2018, p. 233-245.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Theoretical investigations of two adamantane derivatives

T2 - A combined X-ray, DFT, QTAIM analysis and molecular docking

AU - Al-Wahaibi, Lamya H.

AU - Sujay, Subramaniam

AU - Muthu, Gangadharan Ganesh

AU - El-Emam, Ali A.

AU - Venkataramanan, Natarajan S.

AU - Al-Omary, Fatmah A.M.

AU - Ghabbour, Hazem A.

AU - Percino, Judith

AU - Thamotharan, Subbiah

PY - 2018/5/5

Y1 - 2018/5/5

N2 - A detailed structural analysis of two adamantane derivatives namely, ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(phenyl)isothioureido]acetate I and ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(4-fluorophenyl)isothioureido]acetate II is carried out to understand the effect of fluorine substitution. The introduction of fluorine atom alters the crystal packing and is completely different from its parent compound. The fluorine substitution drastically reduced the intermolecular H⋯H contacts and this reduction is compensated by intermolecular F⋯H and F⋯F contacts. The relative contributions of various intermolecular contacts present in these structures were quantified using Hirshfeld surface analysis. Energetically significant molecular pairs were identified from the crystal structures of these compounds using PIXEL method. The structures of I and II are optimized in gas and solvent phases using the B3LYP-D3/6-311++G(d,p) level of theory. The quantum theory of atoms-in-molecules (QTAIM) analysis was carried out to estimate the strengths of various intermolecular contacts present in these molecular dimers. The results suggest that the H–H bonding take part in the stabilization of crystal structures. The experimental and theoretical UV–Vis results show the variations in HOMO and LUMO energy levels. In silico docking analysis indicates that both compounds I and II may exhibit inhibitory activity against 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD1).

AB - A detailed structural analysis of two adamantane derivatives namely, ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(phenyl)isothioureido]acetate I and ethyl 2-[(Z)-1-(adamantan-1-yl)-3-(4-fluorophenyl)isothioureido]acetate II is carried out to understand the effect of fluorine substitution. The introduction of fluorine atom alters the crystal packing and is completely different from its parent compound. The fluorine substitution drastically reduced the intermolecular H⋯H contacts and this reduction is compensated by intermolecular F⋯H and F⋯F contacts. The relative contributions of various intermolecular contacts present in these structures were quantified using Hirshfeld surface analysis. Energetically significant molecular pairs were identified from the crystal structures of these compounds using PIXEL method. The structures of I and II are optimized in gas and solvent phases using the B3LYP-D3/6-311++G(d,p) level of theory. The quantum theory of atoms-in-molecules (QTAIM) analysis was carried out to estimate the strengths of various intermolecular contacts present in these molecular dimers. The results suggest that the H–H bonding take part in the stabilization of crystal structures. The experimental and theoretical UV–Vis results show the variations in HOMO and LUMO energy levels. In silico docking analysis indicates that both compounds I and II may exhibit inhibitory activity against 11-β-hydroxysteroid dehydrogenase 1 (11-β-HSD1).

KW - 11-β-HSD1

KW - Adamantane

KW - Chair conformation

KW - H–H bonding

KW - PIXEL

KW - QTAIM

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U2 - 10.1016/j.molstruc.2018.01.064

DO - 10.1016/j.molstruc.2018.01.064

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EP - 245

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