Enantioselective Mechanism of the Whelk-O1 Chiral Stationary Phase: A Molecular Dynamics Study
Bibliographic record
Abstract
The Whelk-O1 chiral stationary phase is widely used in liquid and supercritical chromatography for the separation of enantiomers. The enantioselective mechanism of the Whelk-O1 chiral stationary phase is the main focus of this thesis. Semi-flexible models are developed based on ab initio calculations for the Whelk-O1 selector and a series of chiral analytes. Extensive molecular dynamics simulations are then applied to study the solvation, selectivity and in silico optimization of the chiral stationary phase. The solvation of the Whelk-O1 chiral stationary phase has been explored in a normal phase n-hexane/2-propanol solvent, a reversed phase water/methanol solvent, and a supercritical CO2/methanol solvent. We found that, in all three solvents, the Whelk-O1 selectors are open to the bulk, indicating readiness for docking of analyte. Significant solvent partitioning at the interfaces was noticed, which generates a polarity gradient between the stationary phase and the bulk, and may encourage a high analyte concentration at the interface. Hydrogen bonding activities on the amide hydrogen, amide oxygen, and nitro oxygen of the Whelk selector have also been analyzed. The selectivity of the Whelk selector was studied by molecular dynamics simulations of analyte docking on the chiral stationary phase. The elution orders and the separation factors for a series of analytes were predicted successfully. We found that hydrogen bonding and π-π stacking interactions are essential for the enantioselectivity as they are strong and specific, and they hold analytes to the cleft region of the Whelk selector. Other interactions, both stabilizing interactions such as the CH-π interaction and the edge-to-face π-π interaction, and destabilizing interactions such as steric hindrance and unfavorable conformational changes also contribute to the enantioselectivity. We identified a dominant docking arrangement for the most retained enantiomers. Other docking arrangements were found to be more frequent for the least retained enantiomers and these involve interactions with alternative selector sites. Based on the identified enantioselective mechanism obtained from the study, an optimization of the Whelk-O1 chiral stationary phase was undertaken and in silico evaluation of the modified chiral stationary phases was carried out. It was demonstrated that restriction of the alternative docking arrangements for the least retained enantiomers could possibly improve the enantioselectivity of the chiral stationary phase.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".