Molecular modelling of structural changes which affect chromatographic selectivity in chiral separations.

Area of Science:

• Chiral Chromatography
• Computational Chemistry
• Molecular Modeling

Background:

• Derivatized silica stationary phases are crucial for enantiomeric separations in chromatography.
• Understanding the molecular interactions governing chiral recognition is essential for optimizing chromatographic performance.

Purpose of the Study:

• To model chromatographic systems using molecular mechanics to predict enantiomeric separation.
• To investigate the influence of stationary phase structure, specifically spacer chain length, on chiral resolution.

Main Methods:

• Utilized the MM2 molecular mechanics program to model stationary phases and chiral analytes.
• Located stable conformers of derivatized silica phases and enantiomers of 2,2,2-trifluoroanthrylethanol (TFAE).
• Performed docking calculations between TFAE enantiomers and stationary phase conformers.

Main Results:

• MM2 calculations correctly predicted the elution order and resolving power for TFAE on valine and alanine phases with n-butyl spacers.
• Varying the spacer chain length (methyl, ethyl, n-propyl) demonstrated its critical role in enantiomeric fractionation.
• Calculations with n-propyl spacers accurately predicted elution order and resolving power, while ethyl and methyl spacers did not.

Conclusions:

• Molecular mechanics modeling is a valuable tool for predicting and understanding chiral chromatographic separations.
• The length of the alkyl spacer chain on derivatized silica stationary phases significantly impacts enantiomeric resolution.
• Optimizing spacer chain length is key to enhancing the performance of chiral stationary phases for specific analytes.