Chiral Separations

Ward, Timothy J.

doi:10.1021/ac000841o

Cited by 75 publications

(34 citation statements)

References 166 publications

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“…Chiral analysis has previously been achieved using various chiral selectors such as cyclodextrins (CDs) [6][7][8][9][10], antibiotics [11][12][13][14], and crown ethers [15][16][17][18]. However, despite good chiral recognition ability, these chiral selectors have several limitations resulting from low solubility, high cost, and difficult synthetic procedures.…”

Section: Introductionmentioning

confidence: 99%

Determination of Enantiomeric Compositions of Analytes Using Novel Fluorescent Chiral Molecular Micelles and Steady State Fluorescence Measurements

et al. 2007

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Novel fluorescent chiral molecular micelles (FCMMs) were synthesized, characterized, and employed as chiral selectors for enantiomeric recognition of non-fluorescent chiral molecules using steady state fluorescence spectroscopy. The sensitivity of the fluorescence technique allowed for investigation of low concentrations of chiral selector (3.0×10 −5 M) and analyte (5.0×10 −6 M) to be used in these studies. The chiral interactions of glucose, tartaric acid, and serine in the presence of, and poly(sodium N-undecanoyl-L-phenylalininate) [poly-SUF] were based on diastereomeric complex formation. Poly-L-SUW had a significant fluorescence emission spectral difference as compared to poly-L-SUY and poly-L-SUF for the enantiomeric recognition of glucose, tartaric acid, and serine. Studies with the hydrophobic molecule α-pinene suggested that poly-L-SUY and poly-L-SUF had better chiral discrimination ability for hydrophobic analytes as compared to hydrophilic analytes. Partial-least-squares regression modeling (PLS-1) was used to correlate changes in the fluorescence emission spectra of poly-L-SUW due to varying enantiomeric compositions of glucose, tartaric acid, and serine for a set of calibration samples. Validation of the calibration regression models was determined by use of a set of independently prepared samples of the same concentration of chiral selector and analyte with varying enantiomeric composition. Prediction ability was evaluated by use of the root-mean-square percent relative error (RMS%RE) and was found to range from 2.04 to 4.06%.

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Section: Introductionmentioning

confidence: 99%

Determination of Enantiomeric Compositions of Analytes Using Novel Fluorescent Chiral Molecular Micelles and Steady State Fluorescence Measurements

et al. 2007

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“…This implies the development of chiral sorting strategies that correspond to the ability to separate two entities that only differ by their handedness. Established chiral separation techniques at molecular scale are mostly based on the recognition of material chirality by another material that is designed to distinguish between the left-and right-handed versions of the entity to be sorted 1,2 . Instead, passive approaches free from such chiral recognition may also be considered, for instance by relying on transport phenomena, as discussed in the early 70s 3 .…”

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confidence: 99%

Optofluidic sorting of material chirality by chiral light

2014

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International audienceThe lack of mirror symmetry, chirality, plays a fundamental role in physics, chemistry and life sciences. The passive separation of entities that only differ by their handedness without need of a chiral material environment remains a challenging task with attractive scientific and industrial benefits. To date, only a few experimental attempts have been reported and remained limited down to the micron scale, most of them relying on hydrodynamical forces associated with the chiral shape of the micro-objects to be sorted. Here we experimentally demonstrate that material chirality can be passively sorted in a fluidic environment by chiral light owing to spin-dependent optical forces without chiral morphology prerequisite. This brings a new twist to the state-of-the-art optofluidic toolbox and the development of a novel kind of passive integrated optofluidic sorters able to deal with molecular scale entities is envisioned

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“…The degree of racemization is then measured by an appropriate analytical method. 12 The interconversion of CP-465021 13 was measured in 3-methyl-butane-1-ol with 3% toluene added to assist UV detection. 10 Because flow technology is automated and programmable, samples for six time points were collected in duplicate at four temperatures (125, 130, 135, and 140°C) in a single overnight run (Table 1, entries 1−5).…”

mentioning

confidence: 99%

Measurement of Atropisomer Racemization Kinetics Using Segmented Flow Technology

Davoren

Bundesmann

Yan

et al. 2012

ACS Med. Chem. Lett.

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When stable atropisomers are encountered by drug discovery teams, they can have important implications due to potential differences in their biological activity, pharmacokinetics, and toxicity. Knowledge of an atropisomer's activation parameters for interconversion is required to facilitate informed decisions on how to proceed. Herein, we communicate the development of a new method for the rapid measurement of atropisomer racemization kinetics utilizing segmented flow technology. This method leverages the speed, accuracy, low sample requirement, safety, and semiautomated nature of flow instrumentation to facilitate the acquisition of kinetics data required for experimentally probing atropisomer activation parameters. Measured kinetics data obtained for the atropo isomerization of AMPA antagonist CP-465021 using segmented flow and traditional thermal methods were compared to validate the method. KEYWORDS: Atropisomer, Reaction kinetics, Segmented flow chemistry T he incidence of axial chirality known as atropisomerism 1 in chemical research is steadily increasing due to the advent of new chemical methodologies, which have made sterically encumbered bonds more facile to form. 2 Their existence in a drug discovery setting can have important implications due to possible differences in their biological activity, pharmacokinetics, and toxicity. 3 Knowledge of atropisomer activation parameters facilitates informed decisions about appropriate handling, storage, and reaction conditions. These data can also influence preclinical development strategy. 4 Herein, we report the rapid measurement of atropisomer racemization kinetics utilizing segmented flow technology. This method leverages the speed, accuracy, low sample requirement, safety, and semiautomated nature of flow instrumentation 5 to facilitate convenient acquisition of the kinetics data required for experimentally probing activation parameters.We demonstrate the utility of this method by employing it to generate kinetics data for CP-465021 (Figure 1), a potent and selective noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist whose synthesis and resolution are reported elsewhere. 6−9 This molecule has an axial element of chirality due to hindered rotation of the N-aryl bond. Previously, serial measurements of the chiral stability of this molecule were conducted in a thermally controlled oil bath in 3-methylbutan-1-ol at 120°C. These experiments suggest that interconversion of CP-465021 occurs via a planar, nonionic transition state with a rate constant k rac = 1.07 × 10 −2 min −1 . 10 Segmented flow technology 11 is uniquely suited for measuring thermal interconversion kinetics and has several advantages over traditional methods. First, the reaction temperature can be maintained safely above the boiling point of solvent due to the instrument's ability to contain pressure, thus accelerating reaction times and data acquisition. Second, the thermal mass of the system is much greater than the reaction fluid permitti...

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Chiral Separations

Cited by 75 publications

References 166 publications

Determination of Enantiomeric Compositions of Analytes Using Novel Fluorescent Chiral Molecular Micelles and Steady State Fluorescence Measurements

Determination of Enantiomeric Compositions of Analytes Using Novel Fluorescent Chiral Molecular Micelles and Steady State Fluorescence Measurements

Optofluidic sorting of material chirality by chiral light

Measurement of Atropisomer Racemization Kinetics Using Segmented Flow Technology

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