Chiral Separation Of Enantiomers Research Articles

Computing metasurfaces enabled chiral edge image sensing

SummaryComputing metasurfaces have shown the extraordinary ability to precisely perform optical analog operations to the input light wave, and therefore exhibit greater potentials toward sensing applications. Here, we propose a unique application of computing metasurface for chiral edge sensing by incorporating a weak-value amplification technique. The computing metasurface performs the spatial differentiation operations of phase objects and extracts the edge-enhanced images, because the phase gradient generally occurs at the edge. The chirality-induced polarization rotation acts as the preselection state and the spatial differentiation operations in the metasurface provide weak coupling. The amplified pointer shift related to the tiny polarization rotation will eventually lead to an asymmetric edge-enhanced image. Owing to the high sensitivity of the weak-value amplification, we experimentally demonstrate a high-contrast recognition of chirality by edge detection, which may have potential applications in real-time measurement and separation of chiral enantiomers.

Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization

Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was R-VER followed by S-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.

Identification of Bi-2-naphthol and Its Phosphate Derivatives Complexed with Cyclodextrin and Metal Ions Using Trapped Ion Mobility Spectrometry.

The separation of chiral enantiomers has gained increasing importance in many research fields, becoming a major research hotspot. 1,1'-Bi (2-naphthol) (BINOL) and 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP) are referred to as atropisomer chiral molecules, which are essential chiral catalysts and intermediates in several reactions. In this work, BINOL and BNP atropisomers are separated and identified using trapped ion mobility spectrometry (TIMS) to monitor the different mobilities of their derivative complexes. The latter are obtained by the simple mixing of BINOL/BNP, cyclodextrin (CD), and the metal ions through noncovalent interactions. The results indicate that the enantiomer complexes of BINOL/BNP can be separated with a certain specificity, showing that R-, S-BINOL can be separated by the ternary complexes of [BINOL+γ-CD + Rb]+, [BINOL+γ-CD + Cu-H]+, and [BINOL+β-CD + Cu-H]+ based on the difference in their mobility; similarly, the R-, S-BNP enantiomer can be isolated by the formed ternary complexes of [BNP+α-CD + Ba-H]+, [BNP+β-CD + Co-H]+, [BNP+β-CD + Ca-H]+, [BNP+β-CD + Cu-H]+, [BNP+β-CD + Fe-H]+, [BNP+β-CD + Li]+, and [BNP+β-CD + Sr-H]+. Furthermore, the peak separation rate (Rp-p) of the complexes was calculated, with the Rp-p of the three enantiomers of BINOL being 1.130 and the Rp-p of the seven complexes of BNP reaching 2.089. At last, the different survival yields for the collision energies were found for the enantiomer complexes, revealing the rigid structural differences in the stereospecificity of the enantiomer complexes that result in the separation by the TIMS. Additionally, due to the advantages of simple operation, fast speed, and high sensitivity and because chemical derivatization and chromatographic separation are not required, the developed method can provide a promising and powerful strategy for the separation and identification of binaphthyl derivatives or even other enantiomers of the reaction intermediates.

Experimental realization of phase-controlled dynamics with hybrid digital\u2013analog approach

Quantum simulation can be implemented in pure digital or analog ways, each with their pros and cons. By taking advantage of the universality of a digital route and the efficiency of analog simulation, hybrid digital–analog approaches can enrich the possibilities for quantum simulation. We use a hybrid approach to experimentally perform a quantum simulation of phase-controlled dynamics resulting from a closed-contour interaction (CCI) within certain multi-level systems in superconducting quantum circuits. Due to symmetry constraints, such systems cannot host an inherent CCI. Nevertheless, by assembling analog modules corresponding to their natural evolutions and specially designed digital modules constructed from standard quantum logic gates, we can bypass such constraints and realize an effective CCI in these systems. Based on this realization, we demonstrate a variety of related and interesting phenomena, including phase-controlled chiral dynamics, separation of chiral enantiomers, and a mechanism to generate entangled states based on CCI.

Chiral and Achiral Enantiomeric Separation of (±)-Alprenolol

AbstractThe chiral separation of enantiomers is crucial for pharmacovigilance within drug discovery. Although a large number of prescribed medications are marketed as pure enantiomers, this is not always the case and many are in fact racemic mixtures. Drug scandals, such as that of Thalidomide in 1961, provide a clear example of the social and economic repercussions that can be caused by negligence of these chiral compounds. Two high performance liquid chromatography (HPLC) methods are presented to determine, separate and quantitate a commonly prescribed chiral beta blocker, (-)-Alprenolol. The first method utilises a chiral column to physically separate the two enantiomers of Alprenolol in 25 minutes, before quantitating with two detectors. Fluorimetry gave the better limit of detection of 0.16-0.41ng and a correlation coefficient of 0.999. The second method used an achiral column coupled with polarimetry to quantitate (-)-Alprenolol without the need for physical separation in 10 minutes. The limit of detection achieved was 27-37μg and demonstrated a correlation coefficient of -0.999.

Optical lateral forces and torques induced by chiral surface-plasmon-polaritons and their potential applications in recognition and separation of chiral enantiomers.

Surface plasmon polaritons carry an intrinsic transverse spin angular momentum which is locked to their propagation direction due to the quantum spin Hall effect of light. We study the chirality-sorting lateral optical forces arising from this phenomenon in a Kretschmann configuration. We show that the characteristics of surface plasmon polaritons are affected by small changes of the environment's chirality. This property can be utilized to detect the medium's chirality in the macro-world. Furthermore, we explain how the the lateral forces and optical torques interact with the chirality of nano-particles located or adsorbed in the vicinity of the surface in the micro-world. Finally, we demonstrate that introducing one handedness of chirality to the dielectric medium in the Kretschmann configuration will benefit the discrimination of chiral enantiomers compared with the nonchiral case. Our work presents physical insights into chirality-selective lateral forces using surface plasmon polaritons and provides a new approach to discriminating and separating chiral enantiomers in the chemical and pharmaceutical industries.

Separation of chiral enantiomers by optical force and torque induced by tightly focused vector polarized hollow beams.

Enantioseparation is important for biology, chemistry and even pharmaceutical industries. We propose an approach for discriminating and separating chiral enantiomers by tightly focused vector polarized hollow beams, which possess a transverse spin angular momentum that can rotate the chiral particles along the transverse direction. We demonstrate the different optomechanical behaviours of the particles upon illumination with different vector polarized (azimuthally and radially) hollow beams by numerically calculating the optical force and spin torque. It is believed that this interesting approach may have potential applications in enantioseparation due to its simplicity and accessibility.

Synthesis and Chiral Separation of Fibratol, Isopropyl 2-(4-((4-chlorophenyl)(hydroxyl) methyl)-phenoxy)-2-methylpropanoate.

Practical synthetic route for the formation of enantiomeric mixture of Isopropyl 2-(4-((4-chlorophenyl)(hydroxyl)methyl)phenoxy)-2-methylpropanoate (Fibratol 2a/b) from isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate (Fenofibrate 1) has been developed. Method has also been established for the chiral separation of enantiomers of Fibratol 2a/b that is synthesized using the route mentioned above. The optical activity determined for enantiomerically separated Fibratol (2a) and Fibratol (2b) are −5.2° and 8.0° which reflect their ability to rotate plane polarized light counterclockwise (levo) and clockwise (dextro), respectively.

Kinetic performance of a 50 mm long 1.8 μm chiral column in supercritical fluid chromatography

Reduced plate heights (hr) of <2 were observed for the first time during the chiral separation of enantiomers, on sub-2μm particles with supercritical fluid chromatography (SFC). The enantiomers of trans-stilbene oxide, were separated on a 4.6×50mm, 1.8μm R,R-Whelk-O1 column, with hr as low as 1.93. The plumbing of a commercial SFC instrument was modified to create a low dispersion version. Without the modification performance was considerably worse.vanDeemter like plots of reduced plate height vs. flow rate, for trans-stilbene oxide, indicate that the optimum flow varied with% modifier. On a 4.6×250mm, 5μm R,R- Whelk-O1 column, the optimum flow was >4mL/min for 5% methanol in CO2, decreasing to <2mL/min for 40% methanol (more than a factor of 2). For a 4.6×50mm column packed with 1.8μm particles the optimum appeared to be near, or >5mL/min with 2.5%, 5%, and 10% methanol, decreasing to between 3 and 3.5mL/min at 40% methanol. This is the first time such shifts have been characterized. Since the solutes were the same in all cases, the differences are likely due to changes in solute diffusion coefficients caused by changes in modifier concentration, and pressure.Pump pressure requirements sometimes exceeded 500bar. It is shown that a 5mL/min flow rate is inadequate for use with 1.8μm particles in a 4.6mm ID column format. Instead, it is suggested to decrease the ID of the column to 3mm, where the optimum flow rates are on the order of 2mL/min with decreased tubing variance. Nevertheless, a number of sub-1min chromatograms are presented.

Dynamical solutions for migration of chiral DNA-type objects in shear flows

We present a dynamical analysis of chiral object motions to explain physical mechanisms and give quantitative predictions on the shear-induced drift motions of chiral objects and the chiral separation of enantiomers using shear flows. For objects well represented by the uniaxial approximation, such as DNA and chiral disk hexamers, dynamical motions in low-Reynolds-number shear flows are solved analytically, in terms of steady-state object-flow interacting parameters, which can be calculated numerically by well-established methods. The shear-induced drifting speed of long helices are evaluated. Good agreements are found between our results and those obtained from dynamical simulations [Makino and Doi, Phys. Fluids 17, 103605 (2005)]. We also compare our results with those obtained experimentally [Marcos, Fu, Powers, and Stocker, Phys. Rev. Lett. 102, 158103 (2009)]. The analysis may also be extended to study other important chiral-flow interactions in nature environments and microfluidic devices, such as the particle-wall and interparticle interactions.

Optically Active Films Fabricated from Poly(Allylamine Hydrochloride) and R-(+)-1-Phenylethylamine Derivatives of Poly(Ethylene-Alt-Maleic Acid) with Different Degrees of Substitution

Optically active films were built up from poly(allylamine hydrochloride) (PAH) and R-(+)--phenylethylamine derivatives of poly(ethylene-alt-maleic acid) (PEMA-PEA) with substituting degrees (DS) ranging from 0.48 to 0.97. The growth of the film was monitored with the circular dichroism (CD) and the UV spectrophotometer and the effect of DS of PEMA-PEA on the film was investigated. UV and CD data show the growth regime of the multilayer changing from exponential to linear. Deposition amounts of PEMA-PEA in multilayer films decrease with the increase in DS of PEMA-PEA, which was explained based on the conformation of the polyelectrolyte and the charge overcompensation as the polyelectrolyte was deposited on the surface of the film. These results are of benefit to the development of multilayer films for the chiral separation of enantiomers.

Investigation of a dual CD chiral CE system for separation of glitazone compounds

A dual CD-CE method for chiral separation of enantiomers of pioglitazone, rosiglitazone and balaglitazone was investigated for the purpose of optimizing the chiral separation. In a previous work a dual CD chiral CE method was used for investigation of glitazone compounds in drug substance and pharmaceutical formulation and the studies showed that all studied glitazones were racemic mixtures. This CE method could separate the enantiomers with a resolution (R(S)) of about 3. However, another study on single glitazone enantiomers pointed out that a higher R(S) is needed to achieve more accurate results for separation of a small amount of one enantiomer in the presence of a high amount of the other enantiomers. The focus of this investigation was thus directed toward the effect of CDs and the pH of the running buffer to achieve a better enantioseparation. Initially CE systems with each of heptakis(2,6-di-O-methyl)-beta-CD (DM-beta-CD) and heptakis(6-sulfobutylether)-beta-CD (SB-beta-CD) as single CD added were investigated at three different pH values (2.5, 5.0 and 9.3). After having chosen the best of these three pH values a dual CD system was further investigated and optimized. The optimization work was then focused on the concentration of the two CDs and the pH of the running buffer and was performed using factorial design experiments. A mixture of a DM-beta-CD and SB-beta-CD was found to be optimal and necessary to achieve enantioseparation with sufficiently high R(S). In order to further verify the importance of the SB-beta-CD, a CE system with the DM-beta-CD added and substitution or partial substitution of the SB-beta-CD by SDS was studied for comparison. (1)H-NMR studies were performed to get a more detailed understanding of the interactions between the glitazones and the CDs used.The optimized dual CD-CE method for chiral separation of the enantiomers of pioglitazone, rosiglitazone and balaglitazone using a running buffer containing 50 mM borate buffer pH 9.7, 12 mM of SB-beta-CD and 3 mM of DM-beta-CD provided a high R(S) (R(S) between 5.5 and 8.8).

Enantiomeric determination of chiral persistent organic pollutants and their metabolites

Many persistent organic pollutants (POPs) are chiral and are generally released into the environment as racemates, but frequently undergo alterations in enantiomeric composition as soon as they are subjected to biochemical processes. Enantiospecific analysis of chiral POPs is important, since enantiomers of chiral compounds often exhibit differences in biological activity, and most biochemical processes in nature are stereospecific. The effects and the environmental fate of the enantiomers of chiral pollutants therefore need to be investigated separately. Chiral separation of enantiomers is one of the most challenging tasks for any analytical technique. We discuss different aspects of enantiospecific analysis of chiral POPs, including classical POPs and their metabolites, as well as some emerging POPs.

Evaluation of enantioselective binding of basic drugs to plasma by ACE

The present paper deals with the evaluation of the stereoselective binding of antihistamines (brompheniramine, chlorpheniramine, hydroxyzine, orphenadrine and phenindamine), phenothiazines (promethazine and trimeprazine) and a local anesthetic (bupivacaine) to human plasma proteins. Since all of them are drugs highly bound to proteins, a methodology to determine the bound fraction of each drug enantiomer was proposed. This methodology includes the incubation of samples containing plasma and racemic drug, ultrafiltration of the mixture and the chiral separation of enantiomers in the bound drug fraction using affinity EKC (AEKC)-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of some antihistamines such as brompheniramine, hydroxyzine, orphenadrine and phenindamine and the phenothiazines, promethazine and trimeprazine, to human plasma proteins. The binding of phenindamine to plasma presented the highest enantioselectivity (ES) (ES = 2.5) followed by trimeprazine (ES = 1.5) and promethazine (ES = 1.4).

Enantioselective Degradation of Rac-Metolachlor and S-Metolachlor in Soil

ABSTRACT Separation of chiral enantiomers and the dissipation of rac-metolachlor and S-metolachlor in soil were evaluated using achiral high-performance liquid chromatography (HPLC) and chiral gas chromatography (GC) methods. Under the experimental conditions the possible metabolite was considered to be N-(2-ethyl-6-methyl-phenyl)-2-hydroxy-acetamide. Because of the presence of two chiral elements (asymmetrically substituted carbon and chiral axis), the baseline separation of metolachlor enantiomers was not achieved. S-metolachlor degraded faster in soil than rac-metolachlor. After a 42-day incubation, 73.4% of rac-metolachlor and 90.0% of S-metolachlor were degraded. However, due to the absence of biological processes the degradation process in sterilized soil showed no enantioselectivity. The results indicated that enantioselective degradations could greatly affect the environmental fate of metolachlor and should be considered when the environmental behavior of these compounds was assessed.

Chiral analysis of pollutants and their metabolites by capillary electromigration methods

Chiral separation of enantiomers is one of the most challenging tasks for any analytical technique including CE. Since the first report in 1985 showing the great possibilities of CE for the separation of chiral compounds, the amount of publications concerning this topic has quickly increased. Although chiral electromigration methods have mainly been used for enantioseparation of drugs and pharmaceuticals, they have also been applied to analyze chiral pollutants. This article intends to provide an updated overview, including works published till January 2005, on the principal applications of CE to the chiral analysis of pollutants and their metabolites, with special emphasis on articles published in the last 10 years. The main advantages and drawbacks regarding the use of CE for chiral separation of pollutants are addressed including some discussion on the foreseen trends of electromigration procedures applied to chiral analysis of contaminants.

Chiral Separation of Enantiomers of a Plant Growth Regulator, Abscisic Acid, by Capillary Electrophoresis with Cyclodextrin Additives

A capillary electrophoresis method for the chiral separation of enantiomers of a plant growth regulator—abscisic acid (ABA) was developed. Five cyclodextrins (CDs) were applied as chiral selectors and it was found that dimethyl‐β‐cyclodextrin (DM‐β‐CD), hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), and γ‐cyclodextrin (γ‐CD) could give satisfactory enantioselectivity. The effects of concentration of the CD, pH value of the buffer, the voltage applied, and the addition of methanol on the chiral separation, were investigated. The best resolution obtained was 3.0, with a 100 mM Tris‐phosphate buffer (pH 5.90) containing 30 mM HP‐β‐CD, and an applied voltage at 15 kV. The reproducibilities of migration times and peak areas were better than 0.6% and 3.2%, respectively. The detection limit of each enantiomer of ABA was 0.30 µg/mL.

ChemInform Abstract: Chiral Separation of Enantiomers via Selector/Selectand Hydrogen Bonding

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Retention and enantioselective properties of ovomucoid-bonded silica columns: Influence of physical properties of base materials and spacer length

The influence of the physical properties of base silica materials and spacer length on chiral separation of enantiomers on ovomucoid (OVM)-bonded materials was investigated. With regard to the pore size of the base silica materials, the 300-Å materials gave higher enantioselectivity, than the 120-Å materials, despite the smaller amounts of bonded OVM proteins. However, higher resolution was obtained with the latter materials. With regard to the spacer length, aminopropyl (AP)-, aminobutyl-, N-(4-aminobutyl)-3-aminopropyl- and N-(6-aminohexyl)-3-aminopropyl-silica gels were activated by N,N′-di-succinimidyl carbonate (DSC) and the proteins were bound. The first two materials showed excellent chiral resolution properties for the solutes tested, and the AP materials gave higher enantioselectivity and resolution. On the other hand, only oxprenolol enantiomers were slightly resolved on the last two materials. Also, AP-silica gels activated by DSC were compared with glycerylpropyl (GP)-silica gels activated by 1,1′-carbonyldiimidazole. The former materials gave higher resolution for acidic and basic solutes despite the lower enantioselectivity, whereas for the unchanged hexobarbital the latter materials gave higher enantioselectivity and almost equal resolution. The above results reveal that the 120-Å base silica gels are more suitable than the 300- Å base silica gels for obtaining larger amounts of bonded OVM proteins and that a less hydrophobic spacer such as an AP group and a hydrophilic spacer such as a GP group are suitable.