Cyclodextrin complexes: Chiral recognition and complexation behaviour

Zsolt Bikádi, Róbert Iványi, Lajos Szente, I. Ilisz, Eszter Hazaia

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cyclodextrins are well known in supramolecular chemistry as host molecules capable of engulfing molecules in their hydrophobic cavity via noncovalent interactions. Although cyclodextrins are frequently used for chiral separation of racemates, the mechanism of chiral recognition has not yet been fully characterised. The current investigation was aimed at examining chiral recognition mechanism in order to construct an in silico method for prediction of chiral recognition. Amino acids were selected as model guest, whereas αCD was used as model host. The results of molecular docking and molecular dynamic calculations were compared to results of stability constant determination and capillary electrophoresis measurements of enantioseparations. Positive correlation between binding strength and chiral separation ability was found. However, the small energy differences between interaction energy of each enantiomer with αCD fell into the range of standard error of molecular docking calculations limiting its applicability for in silico prediction. Examining the stability of complex geometry during molecular dynamics simulation revealed that stable complex geometry is likely to be a prerequisite for chiral recognition. This hypothesis was tested on methylderivatized tryptophan. Indeed, chiral separation of β-methyl-tryptophans by αCD could be successfully predicted by examining the complex geometries during molecular dynamic simulation.

Original languageEnglish
Pages (from-to)282-294
Number of pages13
JournalCurrent Drug Discovery Technologies
Volume4
Issue number4
DOIs
Publication statusPublished - Dec 2007

Fingerprint

Cyclodextrins
Molecular Dynamics Simulation
Computer Simulation
Capillary Electrophoresis
Tryptophan
Amino Acids

Keywords

  • β-Me-tryptophan
  • Alpha-cyclodextrin
  • Amino acids
  • Capillary electrophoresis
  • Complexation
  • Molecular docking
  • Molecular dynamics

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Cyclodextrin complexes : Chiral recognition and complexation behaviour. / Bikádi, Zsolt; Iványi, Róbert; Szente, Lajos; Ilisz, I.; Hazaia, Eszter.

In: Current Drug Discovery Technologies, Vol. 4, No. 4, 12.2007, p. 282-294.

Research output: Contribution to journalArticle

Bikádi, Zsolt ; Iványi, Róbert ; Szente, Lajos ; Ilisz, I. ; Hazaia, Eszter. / Cyclodextrin complexes : Chiral recognition and complexation behaviour. In: Current Drug Discovery Technologies. 2007 ; Vol. 4, No. 4. pp. 282-294.
@article{fa1e28b73be94327ad4a2aff3e033983,
title = "Cyclodextrin complexes: Chiral recognition and complexation behaviour",
abstract = "Cyclodextrins are well known in supramolecular chemistry as host molecules capable of engulfing molecules in their hydrophobic cavity via noncovalent interactions. Although cyclodextrins are frequently used for chiral separation of racemates, the mechanism of chiral recognition has not yet been fully characterised. The current investigation was aimed at examining chiral recognition mechanism in order to construct an in silico method for prediction of chiral recognition. Amino acids were selected as model guest, whereas αCD was used as model host. The results of molecular docking and molecular dynamic calculations were compared to results of stability constant determination and capillary electrophoresis measurements of enantioseparations. Positive correlation between binding strength and chiral separation ability was found. However, the small energy differences between interaction energy of each enantiomer with αCD fell into the range of standard error of molecular docking calculations limiting its applicability for in silico prediction. Examining the stability of complex geometry during molecular dynamics simulation revealed that stable complex geometry is likely to be a prerequisite for chiral recognition. This hypothesis was tested on methylderivatized tryptophan. Indeed, chiral separation of β-methyl-tryptophans by αCD could be successfully predicted by examining the complex geometries during molecular dynamic simulation.",
keywords = "β-Me-tryptophan, Alpha-cyclodextrin, Amino acids, Capillary electrophoresis, Complexation, Molecular docking, Molecular dynamics",
author = "Zsolt Bik{\'a}di and R{\'o}bert Iv{\'a}nyi and Lajos Szente and I. Ilisz and Eszter Hazaia",
year = "2007",
month = "12",
doi = "10.2174/157016307783220549",
language = "English",
volume = "4",
pages = "282--294",
journal = "Current Drug Discovery Technologies",
issn = "1570-1638",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Cyclodextrin complexes

T2 - Chiral recognition and complexation behaviour

AU - Bikádi, Zsolt

AU - Iványi, Róbert

AU - Szente, Lajos

AU - Ilisz, I.

AU - Hazaia, Eszter

PY - 2007/12

Y1 - 2007/12

N2 - Cyclodextrins are well known in supramolecular chemistry as host molecules capable of engulfing molecules in their hydrophobic cavity via noncovalent interactions. Although cyclodextrins are frequently used for chiral separation of racemates, the mechanism of chiral recognition has not yet been fully characterised. The current investigation was aimed at examining chiral recognition mechanism in order to construct an in silico method for prediction of chiral recognition. Amino acids were selected as model guest, whereas αCD was used as model host. The results of molecular docking and molecular dynamic calculations were compared to results of stability constant determination and capillary electrophoresis measurements of enantioseparations. Positive correlation between binding strength and chiral separation ability was found. However, the small energy differences between interaction energy of each enantiomer with αCD fell into the range of standard error of molecular docking calculations limiting its applicability for in silico prediction. Examining the stability of complex geometry during molecular dynamics simulation revealed that stable complex geometry is likely to be a prerequisite for chiral recognition. This hypothesis was tested on methylderivatized tryptophan. Indeed, chiral separation of β-methyl-tryptophans by αCD could be successfully predicted by examining the complex geometries during molecular dynamic simulation.

AB - Cyclodextrins are well known in supramolecular chemistry as host molecules capable of engulfing molecules in their hydrophobic cavity via noncovalent interactions. Although cyclodextrins are frequently used for chiral separation of racemates, the mechanism of chiral recognition has not yet been fully characterised. The current investigation was aimed at examining chiral recognition mechanism in order to construct an in silico method for prediction of chiral recognition. Amino acids were selected as model guest, whereas αCD was used as model host. The results of molecular docking and molecular dynamic calculations were compared to results of stability constant determination and capillary electrophoresis measurements of enantioseparations. Positive correlation between binding strength and chiral separation ability was found. However, the small energy differences between interaction energy of each enantiomer with αCD fell into the range of standard error of molecular docking calculations limiting its applicability for in silico prediction. Examining the stability of complex geometry during molecular dynamics simulation revealed that stable complex geometry is likely to be a prerequisite for chiral recognition. This hypothesis was tested on methylderivatized tryptophan. Indeed, chiral separation of β-methyl-tryptophans by αCD could be successfully predicted by examining the complex geometries during molecular dynamic simulation.

KW - β-Me-tryptophan

KW - Alpha-cyclodextrin

KW - Amino acids

KW - Capillary electrophoresis

KW - Complexation

KW - Molecular docking

KW - Molecular dynamics

UR - http://www.scopus.com/inward/record.url?scp=37549047660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37549047660&partnerID=8YFLogxK

U2 - 10.2174/157016307783220549

DO - 10.2174/157016307783220549

M3 - Article

C2 - 18045090

AN - SCOPUS:37549047660

VL - 4

SP - 282

EP - 294

JO - Current Drug Discovery Technologies

JF - Current Drug Discovery Technologies

SN - 1570-1638

IS - 4

ER -