Chiral Recognition of Butylone by Methylated β-Cyclodextrin Inclusion Complexes: Molecular Calculations and Two-Level
Luckhana Lawtrakul1, Pisanu Toochinda1
1School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, 99 Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand.
ACS Omega
|January 27, 2025
Summary
Methylated cyclodextrins preferentially bind butylone enantiomers through specific conformations. Methylation sites on cyclodextrins critically influence binding energy and chiral recognition mechanisms for separation applications.
Area of Science:
- Computational Chemistry
- Supramolecular Chemistry
- Analytical Chemistry
Background:
- Butylone enantiomers exhibit complexation behavior with cyclodextrins.
- Methylated β-cyclodextrins are widely used in chiral separations.
- Understanding molecular interactions is key for designing effective chiral selectors.
Purpose of the Study:
- To elucidate the complexation behavior of butylone enantiomers with methylated β-cyclodextrin derivatives.
- To investigate the influence of β-cyclodextrin methylation on binding affinity and conformation.
- To understand the molecular mechanisms of enantioseparation for butylone.
Main Methods:
- Molecular docking simulations.
- AM1 quantum mechanical calculations.
- Factorial design analysis.
Main Results:
- Butylone adopts two distinct conformations within the β-cyclodextrin cavity, with one being preferentially stabilized.
- Methylation at O2, O3, and O6 positions significantly impacts complex stability and solvation.
- Heptakis(2,6-di-O-methyl)-β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin show different enantioseparation mechanisms for butylone.
Conclusions:
- Theoretical calculations corroborate experimental findings on butylone-cyclodextrin interactions.
- Detailed molecular insights into chiral recognition by methylated β-cyclodextrins were obtained.
- Findings facilitate rational design of novel chiral selectors for analytical and separation applications.
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