Development of Ensemble Steric and Electrostatic Chirality Descriptors for Modeling Chromatographic Enantioseparations

Researchers from Vrije Universiteit Brussel (VUB) in Brussels, Belgium have developed a new approach to modeling chromatographic enantioseparations using ensemble steric and electrostatic chirality (ESEC) descriptors. This innovative method has been shown to predict the chromatographic separation of enantiomers with high accuracy, even for structurally diverse pharmaceuticals. The study's findings have significant implications for the development of more efficient and effective methods for enantioseparation.

Key Takeaways:

• The researchers defined chiral molecular descriptors using two distinct approaches: scalar triple products of vectorial molecular properties and descriptors that quantify the amount of twist in the overall molecular shape.
• The descriptors were averaged over a conformational ensemble obtained by molecular dynamics, resulting in the development of ESEC descriptors.
• A pilot validation study was performed using a test set of 43 structurally diverse pharmaceuticals analyzed on a polysaccharide-based chiral stationary phase.
• The best linear regression model (7 descriptors) for the chiral separation featured a low leave-one-out cross-validation error (0.0814) and predicted the elution sequence of the separated enantiomers with high accuracy.
• The research concluded that this is the first time that acceptable linear QSER models were obtained for chiral chromatographic separations of such a chemically diverse set of pharmaceuticals.
• The study was funded by Fonds Wetenschappelijk Onderzoek and Vrije Universiteit Brussel.
• The research team included Pieter De Gauquier, Jordy Peeters, Fardine Ameli, Yvan Vander Heyden, Debby Mangelings, and Kenno Vanommeslaeghe.

Statistics:

• 43 structurally diverse pharmaceuticals were used in the pilot validation study.
• The best linear regression model featured 7 ESEC descriptors.
• The leave-one-out cross-validation error was 0.0814.
• The elution sequence of the separated enantiomers was predicted with high accuracy (21 out of 23 molecules).
• The aRS was predicted with high accuracy for 27 out of 42 molecules.

Sources:

• PLOS One. "Development of Ensemble Steric and Electrostatic Chirality (ESEC) descriptors for modelling chromatographic enantioseparations". Vrije Universiteit Brussel. (2025;20(10)).
• NewsRx. "Findings in the Area of Science Reported from Vrije Universiteit Brussel (VUB)". Medical Devices & Surgical Technology Week. (November 2, 2025; p 488).