Chiral Discrimination Study for Polysaccharide‐Based Chiral Stationary Phases

Ye, Yun K.

doi:10.1002/9780470608661.ch6

Cited by 2 publications

(3 citation statements)

References 47 publications

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“…The structure and the chiral recognition mechanism of the most widely used chiral stationary phases, polysaccharide-based CSPs, have been extensively investigated. ,− The structure of one typical example of polysaccharide-based CSPs often used as the model system is amylose tris(3,5-dimethyphenylcarbamate) (ADMPC), which has been scrutinized via many different experimental techniques, including solid state nuclear magnetic resonance spectroscopy (NMR), NMR in solution using the 2D Nuclear Overhauser Enhancement (NOESY) technique, vibrational circular dichroism (VCD), and attenuated total reflection infrared spectroscopy (ATR-IR) . Yamamoto et al reported that ADMPC possesses a left-handed 4/3 helical structure in chloroform.…”

Section: Introductionmentioning

confidence: 99%

The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase

et al. 2017

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More than half of all pharmaceuticals are chiral compounds. Although the enantiomers of chiral compounds have the same chemical structure, they can exhibit marked differences in physiological activity; therefore, it is important to remove the undesirable enantiomer. Chromatographic separation of chiral enantiomers is one of the best available methods to get enantio-pure substances, but the optimization of the experimental conditions can be very time-consuming. One of the most widely used chiral stationary phases, amylose tris(3,5-dimethylphenyl carbamate) (ADMPC), has been extensively investigated using both experimental and computational methods; however, the dynamic nature of the interaction between enantiomers and ADMPC, as well as the solvent effects on the ADMPC-enantiomer interaction, are currently absent from models of the chiral recognition mechanism. Here we use QM/MM and molecular dynamics (MD) simulations to model the enantiomers of flavanone on ADMPC in either methanol or heptane/2-propanol (IPA) (90/10) to elucidate the chiral recognition mechanism from a new dynamic perspective. In atomistic MD simulations, the 12-mer model of ADMPC is found to hold the 4/3 left-handed helical structure in both methanol and heptane/IPA (90/10); however, the ADMPC polymer is found to have a more extended average structure in heptane/IPA (90/10) than in methanol. This results from the differences in the distribution of solvent molecules close to the backbone of ADMPC leads to changes in the distribution of the (φ, ψ) dihedral angles of the glycoside bond (between adjacent monomers) that define the structure of the polymer. Our simulations have shown that the lifetime of hydrogen bonds formed between ADMPC and flavanone enantiomers in the MD simulations are able to reproduce the elution order observed in experiments for both the methanol and the heptane/IPA solvent systems. Furthermore, the ratios of hydrogen-bonding-lifetime-related properties also capture the solvent effects, in that heptane/IPA (90/10) is found to make the separation between the two enantiomers of flavanone less effective than methanol, which agrees with the experimental separation factors of 0.9 versus 0.4 for R/S, respectively.

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Section: Introductionmentioning

confidence: 99%

The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase

et al. 2017

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“…66,69 In applications, the polysaccharide selector is The structure and the chiral recognition mechanism of the polysaccharide-based CSPs, have been extensively investigated. 50,71,72 The structure of one typical example of polysaccharide-based…”

Section: Simulations Of Chiral Analytes On Prolinetype Selectorsmentioning

confidence: 99%

“…The structure and the chiral recognition mechanism of the polysaccharide-based CSPs, have been extensively investigated. 50,71,72 The structure of one typical example of polysaccharide-based CSPs, often used as the model system, is amylose tris(3,5dimethyphenylcarbamate) (ADMPC) has been investigated using different experimental techniques, including solid state nuclear magnetic resonance spectroscopy (NMR), 73 NMR in solution using the 2D Nuclear Overhauser Enhancement (NOESY) technique, 74 vibrational circular dichroism (VCD), 75 attenuated total reflection infrared spectroscopy (ATR-IR), and x-ray diffraction. 50 Yamamoto et al 76 reported that ADMPC possesses a left-handed 4/3 helical structure in chloroform, while Ma et al 45 used VCD measurements, which also suggested a left-handed helical structure.…”

Section: Simulations Of Chiral Analytes On Prolinetype Selectorsmentioning

confidence: 99%

Molecular dynamics simulations of enantiomeric separations as an interfacial process in HPLC

2021

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Since chromatographic separation is a dynamic process, with the interactions between the drug and the chiral stationary phase mediated by the solvent, no single interacting structure, such as could be found by minimizing the energy, could possibly describe and account for the ratio of residence times in the chromatographic column for the enantiomeric pair. We describe the use of explicit-solvent fully atomistic molecular dynamics simulations, permitting all the interactions between the atoms constituting the chiral stationary phase, solvent molecules and the drug molecule. This allows us to better understand the molecular dynamic chiral recognition that provides the discrimination, which results in the separation of enantiomers by high performance liquid chromatography. It also provides a means of predicting, for a given set of conditions, which enantiomer elutes first and an estimate of the expected separation factor. In this review, we consider the use of molecular dynamics toward this understanding and prediction.

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Chiral Discrimination Study for Polysaccharide‐Based Chiral Stationary Phases

Cited by 2 publications

References 47 publications

The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase

The Composition of the Mobile Phase Affects the Dynamic Chiral Recognition of Drug Molecules by the Chiral Stationary Phase

Molecular dynamics simulations of enantiomeric separations as an interfacial process in HPLC

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