Enrichment Of Enantiomers Research Articles

Chiral signatures of polychlorinated biphenyls in serum from e-waste workers and their correlation with hydroxylated metabolites.

Elevated concentrations of polychlorinated biphenyls (PCBs) found in environmental media and biota from typical e-waste dismantling sites have raised concerns regarding their human body burden and potential negative health effects. In the present study, the enantiomeric compositions of three typical chiral congeners (PCB-95, PCB-132, and PCB-149) were measured in 24 serum samples from e-waste workers by using gas chromatography coupled to triple quadrupole tandem mass spectrometry. The mean enantiomer fractions (EFs) of chiral congeners in serum from the workers were 0.655±0.103, 0.679±0.164, and 0.548±0.095 for PCB-95, PCB-132, and PCB-149, respectively. The (+) enantiomers of PCB-95, PCB-132, and PCB-149 were enantioselectively enriched in serum. Significant positive correlations were observed between the EF of the chiral congener PCB-95 and the total concentration of OH-PCBs, suggesting that EF values of chiral PCBs could be used to indicate the extent of biological metabolism. In addition, the EF of PCB-95 in serum samples increased with increasing work duration of the e-waste workers, thus demonstrating the usefulness of EF values of chiral PCBs as tracers of human exposure to PCBs. Because of the enantioselective enrichment of (+) enantiomers of PCB-95, PCB-132, and PCB-149, further studies are needed to explore the metabolism and toxicity of chiral contaminants in humans.

Stereoselective enrichment and determination of citalopram enantiomers by cation-selective exhaustive injection and sweeping coupled with cyclodextrin modified electrokinetic chromatography

An highly sensitive, rapid and enantioselective method was developed for the enantioseparation and determination of citalopram enantiomers by cation selective exhaustive injection-sweeping-cyclodextrin modified electrokinetic chromatography (CSEI-sweeping-CDEKC). The optimized conditions were: 50 mM pH 3.0 phosphate solution with 25 mg·mL−1 S-β-CD used as background buffer, 50 mbar 300 s hydrodynamical injection of 150 mM pH 3.0 NaH2PO4 buffer followed with 5 s water plug, 10 kV 600 s electrokinetic sample injection, -20 kV CDEKC run. Under the optimized conditions, the resolution was Rs=8.04, the enrichment factor as up to 2163 folds, the LOD values were: 3.6 ng·mL−1 for R-citalopram, 4.1 ng·mL−1 for S-citalopram, and 3 ng·mL−1 for both enantiomers in plasma samples. This new method showed good precision, repeatability and stability, which had been successfully applied to the impurity inspection of escitalopram oxalate and the stereoselective pharmacokinetic study of citalopram enantiomers.

Accumulation of chiral pharmaceuticals (ofloxacin or levofloxacin) onto polyethylene microplastics from aqueous solutions

Drug chirality is attracting increasing attention because the enantiomers of the same chiral pharmaceutical usually exhibit different biological activities, metabolic pathways, and toxicities. The ubiquitous presence of microplastics (MPs) can enrich organic pollutants commonly found in the environment. However, knowledge about the enrichment of pharmaceutical enantiomers to MPs is relatively limited. We investigated the occurrence of enantioselectivity of ofloxacin (OFL) and levofloxacin (LEV) in the adsorption processes on polyethylene (PE) and the interactions influenced by environmental factors. The results showed that the adsorption efficiency of OFL was generally 3–5% (p < 0.05) higher than that of LEV, indicating the different affinities of the enantiomers to PE, but the adsorption process of OFL and LEV on PE was both well described by pseudo-first-order kinetics and liner isotherm models. The chirality of OFL and LEV was not affected by sizes of PE particles and solution salinity due to the identical physicochemical properties. An examination of pH effect indicated that OFL showed better acid-base adaptability than LEV. Moreover, the differences in enantiomeric enrichment between OFL and LEV on PE were promoted with increasing UV light exposure time and natural organic matter (NOM) concentrations. Using Fourier transform infrared spectroscopy (FTIR), we demonstrated that the constituents of the functional groups in chiral NOM were greatly related to the enantiomer stereoselectivity of OFL, subsequently affecting their adsorption in a chiral environment. The excitation-emission matrix (EEM) spectra confirmed the enantioselective behaviors of chiral pharmaceuticals under UV light due to the different optical activity and humic acid-like and fulvic acid-like molecular structure of the enantiomers. These findings imply that the enantioselectivity of drug enantiomers should be considered in presence of microplastics, leading to a more accurate environmental fate and risks assessments of chiral pharmaceuticals.

Origin of Kinetic Resolution of Hydroxy Esters through Catalytic Enantioselective Lactonization by Chiral Phosphoric Acids.

Kinetic resolution is a widely used strategy for separation and enrichment of enantiomers. Using density functional theory computations, the origin of how a chiral BINOL-phosphoric acid catalyzes the selective lactonization of one of the enantiomers of α-methyl γ-hydroxy ester is identified. In a stepwise mechanism, the stereocontrolling transition state for the addition of the hydroxyl group to the si face of the ester carbonyl in the case of the S isomer exhibits a network of more effective noncovalent interactions between the substrate and the chiral catalyst.

Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples.

A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe3O4 nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 μg∙mL−1 for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25–5.0 μg∙mL−1 (R2 > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples.

Planar chiral asymmetric naphthalenediimide cyclophanes: synthesis, characterization and tunable FRET properties

A series of planar chiral asymmetric naphthalenediimide (NDI) cyclophanes () consisting of two different NDIs interlinked by rigid meta-dimethylenebenzene spacers was synthesized. A modular synthetic strategy based on the dichloro cyclophane as common precursor gave a straightforward access to racemic mixtures of the NDI cyclophane dyes . In particular the substitution of both chlorine atoms of by tert-butylsulfanyl-, methoxy- and piperidinyl-groups provided racemic mixtures of the fluorescent NDI cyclophane dyes , and respectively. Fluorescence spectroscopy revealed chemically tuneable intramolecular FRET properties, as the spectral overlap between the emission of the unsubstituted NDI and the absorption of the core-substituted NDI subunit of the cyclophane could be adjusted by the core substituents. The racemic nature of the samples of cyclophanes , and in the case of the di-tert-butylsulfanyl functionalized cyclophane the enrichment of both enantiomers, was demonstrated by HPLC using a chiral stationary phase. The solid state structure of was determined by X-ray analysis. A periodic arrangement of both enantiomers of the planar chiral cyclophane in pillars such that NDI- and 2,6-core substituted NDI chromophores alternate periodically was observed.

MEMBRANE-ASSISTED CHIRAL RESOLUTION OF PHARMACEUTICALS: IBUPROFEN SEPARATION BY ULTRAFILTRATION USING BOVINE SERUM ALBUMIN AS CHIRAL SELECTOR

The chiral separation of ibuprofen has been performed by ultrafiltration in solutions containing the protein bovine serum albumin (BSA) as a chiral selector. The effectiveness of optical resolution was characterized in terms of enantiomeric enrichment and solute recovery in the permeate. Working conditions, including parameters of feed solution and hydrodynamic conditions, which can influence thermodynamic equilibrium and nonselective solute binding, have been investigated with regard to the separation effectiveness. Enantioselectivity is strongly pH-dependent and reaches a maximal value at pH 9.0–9.2. It was established that nonspecific interactions also played a significant role in total ibuprofen binding, decreasing both enantioselectivity and solute recovery in permeates. Nonspecific interactions are suppressed in the presence of organic solvents (acetonitrile, methanol) in the feed solution thereby increasing the solute recovery in the permeate. Increase in BSA content in the feed solution results in an increase of both enantioselectivity and solute binding. In ultrafiltration-based chiral separation, concentration polarization and gel formation worsen enantioselectivity and increase solute binding. A consequent enrichment of enantiomers was illustrated in a multi-stage chiral resolution. After six stages of separation, the permeate contains more than 95% of (S)-ibuprofen. Regeneration of both BSA and bound enantiomer may be fulfilled in the same ultrafiltration system by ultrafiltration of alkaline solutions.

Enantiomeric Enrichment of Stereolabile Chiral Spiro Compounds by Dynamic HPLC on Chiral Stationary Phases

The separation and enrichment of enantiomers can be combined by HPLC on chiral stationary phases. One requirement for success is that the components of the racemate—as, for example, with 1—undergo thermal interconversion. In the two-column system shown below the enantiomers are partially separated in the first column at low temperature. The chromatographic flow is then stopped to allow the first fraction eluted (A) to equilibrate on the second column.

Lignin model glycosides: preparation and optical resolution

R. F. Helm, M. Toikka, K. Li and G. Brunow, J. Chem. Soc., Perkin Trans. 1, 1997, 533 DOI: 10.1039/A603786K

The Enantiomers of Indolino Spiro Compounds. Barriers to Thermal Cleavage of Their C(sp3)-O BOND*

Abstract The enantiomers of the title compounds were separated for the first time by liquid chromatography (LC) on optically active sorbents analytically or preparatively. They were characterized mainly by their retention factors and by circular dichroism. Barriers to thermal cleavage of the C(sp3)-O bond were mainly determined by a combination of polarimetry and LC without preparative enrichment of enantiomers. These Δ# 1−values (81.5 − 99.2 kJ/mol) are discussed with reference to substitution; it is concluded that the C-O bond in oxazines (Table IV, X = NB) is broken less easily than the one in pyrans (X = CH). These thermal enantiomerizations (Scheme 1) are examples of fast valence isomerizations.

Helical Phenanthrenes, 3[1] Syntheses, Enrichment of Enantiomers, and Barriers to Racemization of Twisted 9, 10‐Phenanthrenequinones

The known syntheses of the 9, 10‐phenanthrenequinones 10a – c were improved by the chlorotrimethylsilane modification of the acyloin condensation of biaryl diesters. The novel quinones 4a, 4b, and 12 were prepared. For the first time, enantiomers (M and P) of this class of compounds were enriched semipreparatively by liquid chromatography on optically active sorbents. The barriers to thermal racemization amount to 90 – 130 kJ mol‐1 (Table 2) and are thus higher than the barriers for the corresponding phenanthrene hydrocarbons by roughly 20 kJ mol‐1. The reasons for this increase are discussed in terms of repulsive interactions in the transition state of helix inversion.

Chiroptical detection during liquid chromatography: III. Non-stop acquisition of circular dichroism spectra during liquid chromatography

A new type of spectrometer, built in-house, served as a circular dichroism detector for liquid chromatography. It acquired differential absorbances Δ A = f(λ) at all wavelengths, λ, between 208 and 268 nm simultaneously within a time interval of 9 s. Non-stop acquisition of circular dichroism spectra during liquid chromatography is described for the first time. The novel set-up gives automatic access to dichrograms without preparative enrichment of enantiomers, if some analytical separation on an optically active sorbent can be achieved. Like photodiode-array detection, the new technique collects ultraviolet spectra A = f(λ), but furnishes positive/negative information Δ A = f(λ) in addition. It was applied to (±)-2,2′-spirobi[2 H-chromene] as a test sample and microcrystalline tribenzoylcellulose as a sorbent. Future applications of non-stop liquid chromatographic circular dichroic-ultraviolet data are discussed.

Intra‐ und extraannular funktionalisierte helical‐chirale [2.2]Metacyclophane: Synthese, Circulardichroismus und Struktur‐Chiroptik‐Beziehungen

Intra‐ und Extraannularly Functionalized Chiral [2.2]Metacyclophanes: Synthesis, Circular Dichroism, and Structure ‐ Chiroptic RelationshipsA simple one‐step cyclization reaction for the synthesis of the title compounds 1‐5 is presented; separation (enrichment) of enantiomers is achieved by HPLC mainly on (+)‐PTrMA. The kinetics of interconversion (racemization) of the new dihetera[2.2]metacyclophanes are determined: No racemization of the internally substituted phanes is found on heating until decomposition, whereas the extraannularly substituted compounds exhibit barriers of interconversion of about 130 kJ/mol, similar to that of the unfunctionalized skeleton 1a. For the pyridinophane 2 the barrier (110 kJ/mol) is lower corresponding to the decreased spatial requirement of the nitrogen lone pair compared to a C‐H bond. The circular dichroism curves of the intraannularly functionalized phanes are compared with those of the extraannularly functionalized reference compounds: A bathochromic shift of the Cotton effect at short wavelengths is found, which is increasing with the bulkiness of the internal functional group.

Chirale dreilagige und kondensierte [2.2]Cyclophane Synthese, Struktur, Chiroptik

Chiral Triple‐Layered and Condensed [2.2]Cyclophanes ‐ Synthesis, Structure, Chiroptical PropertiesThe helical title compounds 1‐5 are obtained using a simple one‐step cyclisation reaction with yields reaching or increasing those obtained by application of organometallic methods in [2.2]phane syntheses. The formation of the triple‐layered phanes 1 leads with high selectivity only to the “up‐down” isomers with fixed conformation, as shown by X‐ray crystallography and by the detection of strong NOEs of the inner hydrogen atoms. For studies on structure‐chiroptic relation‐ships a systematic sequence of helical [2.2]phanes with larger arene systems is synthesized. Enrichment of enantiomers is achieved by HPLC on (+)‐PTrMA; the kinetics of racemisation and the CD spectra are discussed.

Optical enrichment of dansyl-rac-amino acids by formation of crystalline inclusion complexes with cyclodextrins.

Optical enrichment from racemic dansyl-leucine, dansyl-norleucine, and dansyl-phenylalanine with both beta- and gamma-cyclodextrins in water is reported. Initial crystallization yielded the dansyl-L-Leucine isomer complexed in excess with beta-cyclodextrin with an optical purity of 62-78% depending on experimental conditions. The optical purities obtained for L-norleucine and L-phenylalanine were 71 and 64%, respectively. The optical purity can be increased with continued recrystallization. The dansyl-D-leucine isomer was obtained in the mother liquor with an optical purity of 54-93% depending on experimental conditions. The optical purities obtained for D-norleucine and D-phenylalanine were 72 and 58%. The optical purity of the isomer depended on the molar ratio of host:guest and the pH value of the solution. Optimum enrichment of both enantiomers was achieved with host:guest ratios of 2:1 and 3:1. Although maximum crystalline yield of the dansyl-leucine/CD inclusion complex was obtained at a pH of 3.5, optical purity of both enantiomers was less than that obtained at other pHs. The influence of the molar ratio of host:guest and the pH value of the solution are discussed. This method is suitable for large-scale enantiomeric separations.

Chiroptical detection. Novel possibilities of its application to enantiomers

Polarimetric and/or circular dichroic detection of enantiomers after liquid chromatography on optically active sorberts has been used for the following purposes: determination of enantiomeric purity in spite of peak overlap, investigation of enantiomerization during chromatography, monitoring of racemizations and recording of circular dichrograms without preparative enrichment of enantiomers. Novel examples for all applications are give. The general prospects for chiroptical detection are discussed.

Enrichment of enantiomers and other isomers with aqueous liquid membranes containing cyclodextrin carriers.

Enrichment of enantiomers and other isomers with aqueous liquid membranes containing cyclodextrin carriers.

ChemInform Abstract: Enantioselective Acetal Formation. A Process for the Pure Preparation or Enrichment of Enantiomers.

AbstractBei der säurekatalysierten Umsetzung der optisch aktiven Acetale (I) mit zwei Äquivalenten der racemischen Alkyl‐aryl‐carbinole (II) entsteht bevorzugt das diastereomere Acetal (III), das zu dem entsprechenden Enantiomeren (II) hydrolysiert wird.

The enantiomers of N,N-dimethylthiobenzamides: Chromatographic behaviour and rotational barriers

N,N-Dimethylthiobenzamides bearing hydrogen atoms in both orthopositions were shown by 1H NMR in the presence of an optically active alcohol to have non-coplanar π-systems. The barrier to rotation about the C(sp 2-C(sp 2) bond amounts to 43 ± 2 kJ/mol. Liquid chromatography on triacetylcellulose served for the enrichment of enantiomers of 2-substituted thiobenzamides. In several cases considerable enantioselectivity (relative retention up to 8.7) was observed. The barriers to enantiomerization (Tables 3, 4 and 5), determined by thermal racemization, were discussed in terms of non-bonding interactions, electrostatic repulsions and buttressing effects in the transition state of rotation.

Liquid Chromatography on Triacetylcellulose, 6. Synthesis, Chromatographic Enrichment of Enantiomers, and Barriers to Enantiomerization of Helical Phenanthrenes

AbstractEnantiomerization barriers (Table 1) for novel 4,5‐disubstituted phenanthrenes of types A and B have been determined by coalescence of 1H NMR signals or by thermal racemization of chromatographically enriched enantiomers. The barriers depend upon the size of the groups R = CMe3, Br, Me, Cl, OBz in A and B, the behaviour of annelated benzo rings instead of R being particularly considered.