Synthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles

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Abstract

Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity. © 2012 Elsevier Masson SAS. All rights reserved.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume54
DOIs
Publication statusPublished - 1 Aug 2012

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Tryptophan Oxygenase
Indoles
Dipole moment
Isomers
Electronic properties
Solubility
Crystal structure
Mechanics
Static Electricity
X-Ray Diffraction
Freezing
Atoms
Molecules
Quantum theory
X-Rays
Bond length
Melting point
Electrostatics
Single crystals
Crystalline materials

Keywords

  • Chloro-3-(2-pyridin-3-ylvinyl)-1H-indole
  • Crystal structure
  • Human tryptophan 2,3-dioxygenase
  • Isomer
  • Physico-chemical properties

Cite this

@article{686d2f592592476db6c3630e827725db,
title = "Synthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles",
abstract = "Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity. {\circledC} 2012 Elsevier Masson SAS. All rights reserved.",
keywords = "Chloro-3-(2-pyridin-3-ylvinyl)-1H-indole, Crystal structure, Human tryptophan 2,3-dioxygenase, Isomer, Physico-chemical properties",
author = "Laurence Moineaux and Sophie Laurent and J{\'e}r{\'e}my Reniers and Eduard Dolusic and Moreno Galleni and Jean-Marie Fr{\`e}re and Bernard Masereel and Rapha{\"e}l Fr{\'e}d{\'e}rick and Johan Wouters",
note = "Copyright {\circledC} 2012 Elsevier Masson SAS. All rights reserved.",
year = "2012",
month = "8",
day = "1",
doi = "10.1016/j.ejmech.2012.04.033",
language = "English",
volume = "54",
pages = "95--102",
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T1 - Synthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles

AU - Moineaux, Laurence

AU - Laurent, Sophie

AU - Reniers, Jérémy

AU - Dolusic, Eduard

AU - Galleni, Moreno

AU - Frère, Jean-Marie

AU - Masereel, Bernard

AU - Frédérick, Raphaël

AU - Wouters, Johan

N1 - Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity. © 2012 Elsevier Masson SAS. All rights reserved.

AB - Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity. © 2012 Elsevier Masson SAS. All rights reserved.

KW - Chloro-3-(2-pyridin-3-ylvinyl)-1H-indole

KW - Crystal structure

KW - Human tryptophan 2,3-dioxygenase

KW - Isomer

KW - Physico-chemical properties

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U2 - 10.1016/j.ejmech.2012.04.033

DO - 10.1016/j.ejmech.2012.04.033

M3 - Article

VL - 54

SP - 95

EP - 102

JO - European journal of medicinal chemistry / Chimica therapeutica

JF - European journal of medicinal chemistry / Chimica therapeutica

SN - 0223-5234

ER -