Enantiomeric ratios: Why so many notations?

Tiritan, Maria Elizabeth; Fernandes, Carla; Maia, Alexandra S.; Pinto, Madalena; Cass, Quézia B.

doi:10.1016/j.chroma.2018.07.039

Cited by 28 publications

(10 citation statements)

References 73 publications

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“…was determined by the relative percentages of the peak areas according to [e.r. (%) = 100 × ([ R ]/([ R ] + [ S ]) or 100 × ([ S ]/([ S ] + [ R ]), where [ S ] and [ R ] are the area of the peak of each enantiomer 38 …”

Section: Methodsmentioning

confidence: 99%

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

Phyo¹,

Teixeira

Gonçalves

et al. 2021

Chirality

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Liquid chromatography enantioseparation and determination of enantiomeric purity of synthetized xanthone and benzophenone derivatives comprising one or more chiral moieties are reported. High enantioselectivity and resolution were observed in (S,S)‐Whelk‐O1 chiral stationary phase (CSP) for the enantiomeric mixtures of compounds comprising an aromatic ring linked to the stereogenic center(s), with α values ranging from 1.35 to 4.15 and Rs values ranging from 2.22 to 13.87. Among all the tested enantiomeric mixtures, those comprising three chiral moieties positioned in the xanthone scaffold gave the best chromatographic results. Enantiomers comprising an alkyl chain linked to the stereogenic centers were enantioseparated on a Lux® Celullose‐2 CSP. For both CSPs, the elution was performed in polar organic mode. The enantiomeric ratio (e.r.) values were always higher than 99%. Additionally, assessment of chiral recognition mechanisms on (S,S)‐Whelk‐O1 CSP was performed by molecular docking approach, which are in accordance with the chromatographic parameters. The nature and number of chiral moieties in the central aromatic scaffold of either xanthone or benzophenone derivatives are proved to be crucial for enantiorecognition. The evaluation of the growth inhibition of human tumor cell lines revealed that (S,S)‐(+)‐5 was the most potent compound, with values of GI50 of 12.83 ± 2.09 μM for A375‐C5 melanoma, 12.40 ± 1.16 μM for MCF‐7 breast adenocarcinoma, and 13.06 ± 1.29 μM for NCI‐H460 non‐small cell lung cancer. In some cases, the growth inhibitory effects demonstrated to be dependent on the stereochemistry of the compounds.

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Section: Methodsmentioning

confidence: 99%

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

Phyo¹,

Teixeira

Gonçalves

et al. 2021

Chirality

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“…In spite of the application of the diversity of methods for bioanalysis, LC with mass analyzers has become the technique of choice due to its versatility, high selectivity, sensitivity, and the low quantification limits achieved [ 66 ]. Moreover, due to the numerous commercially available chiral stationary phases (CSPs) and the high versatility provided by the multimodal elution conditions, LC has been the most applied technique to quantify enantiomers and to determine the enantiomeric ratio [ 67 , 68 ], for application in pharmaceutical preparations and in biological samples for therapeutic and toxicological purposes [ 69 ]. Regardless, the hard task of new applications relies on the right selection of a CSP and mobile phase conditions, mostly achieved by trial and error, especially considering that in most cases the detection by MS is mandatory and sets a restriction on mobile phase conditions for the enantioseparation.…”

Section: Chiral Analysis In Pharmacokineticsmentioning

confidence: 99%

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

et al. 2021

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Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.

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“…has advantage for expressing selectivity in synthesis and is related to the F I G U R E 1 Structures of epineoclausenamide and neoclausenamide direct results of the chromatograms. 12 Therefore, we use e.r. to express the purity of enantiomeric purity.…”

Section: Introductionmentioning

confidence: 99%

The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate

et al. 2021

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We synthesized the optically active epineoclausenamide by utilizing chiral reagents, such as R-α-methylbenzylamine and S-α-methylbenzylamine, for the resolution of the intermediate (trans-3-phenyl-oxiranecarboxylic acid 12), followed by amide exchange, cyclization, and reduction, unlike previously reported methods. The Meerwein-Ponndorf-Verley reduction was used to asymmetrically reduce neoclausenamidone. A plausible reduction mechanism of this method was elucidated. Thereafter, high-performance liquid chromatography (HPLC) was investigated for the resolution of the epineoclausenamide enantiomers. HPLC was also used to determine the optical purity of these isomers. Two chiral stationary phases (CSPs) for separating the enantiomers were compared. Different mobile phase compositions were tested at 298.15 K. The results showed that the best separation was obtained when the mobile phase was composed of n-hexane and isopropanol (IPA) (75/25, v/v), the racemate was separated on a Chiralcel OJ-H column, and the flow rate was 1.0 mL/min at a wavelength of 210 nm and a temperature of 25 C. The enantiomeric ratio (e.r.) values of both the synthetic (À)-epineoclausenamide and (+)-epineoclausenamide were 1.3(+):98.7(À) and 99.3(+):0.7(À), respectively. In this study, a new synthetic route was designed with a yield of 12.3-14.1%, and a quick (8 min) effective separation method was obtained. This provides basis for pharmacological research and quality control of clausenamide analogues.

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Enantiomeric ratios: Why so many notations?

Cited by 28 publications

References 73 publications

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate

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