Non-racemic Mixtures Research Articles

Identification of 3-hydroxyaspartate with two chiral centers by capillary electrophoresis-mass spectrometry and vibrational circular dichroism independent of single enantiomer standard

Background3-Hydroxyaspartate(3-HA) is a non-proteinaceous amino acid whose four stereoisomers have different biological functions, making it meaningful to separate and analyze them. A combination of capillary zone electrophoresis-mass spectrometry (CZE-MS) and electron circular dichroism enables the separation and analysis of the four stereoisomers of 3-HA, but relies on enantiomeric standards. In contrast, the new method based on vibrational circular dichroism (VCD) can successfully confirm the peak order of the four enantiomers simultaneously without a single enantiomeric standard. This method is suitable for molecules without UV absorption, as well as for molecules with polychiral centers, and does not require enantiomeric standards. ResultsWe present a new analytical method based on CZE-MS coupled with VCD for the simultaneous determination of four stereoisomers of 3-HA with two chiral centers (D-threo-3-hydroxyaspartate, D-THA; L-threo-3-hydroxyaspartate, L-THA; D-erythro-3-hydroxyaspartate, D-EHA; L-erythro-3-hydroxyaspartate, L-EHA) in the absence of an optically pure single enantiomeric standard. The semipreparations of the non-racemic mixtures of DL-THA and DL-EHA were performed using high performance liquid chromatography (HPLC), with enantiomeric excess values reaching 90 %. By comparing the experimental VCD spectra of the DL-THA/DL-EHA mixture with the theoretical VCD spectra of the single L-THA/L-EHA enantiomer, the configuration of the dominant enantiomer in the nonracemic mixture was determined, where the two characteristic peaks in the 1250-1750 cm−1 spectral range fitted well. Finally, combined with the comparison of CE peak areas, the four stereoisomers were identified successfully. SignificanceThis is the first combined CZE-MS and VCD method for the simultaneous separation and analysis of four stereoisomers of 3-HA without relying on enantiomeric standards. This method is simple and reliable, and provides a new idea for the separation and analysis of chiral compounds with polychiral centers, which are difficult to obtain from enantiomeric standards.

Simultaneous identification and enantioseparation of ofloxacin and duloxetine without the single standard and computational calculation of their inclusion complexes.

Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.

Altering the mobile phase composition to enhance self-disproportionation of enantiomers in achiral chromatography

The influence of mobile phase composition on the efficiency of enantiomer separation by achiral chromatography (ACh) was investigated. The separation was induced by the phenomenon of self-disproportionation of enantiomers (SDE) triggered by their homo and hetero-chiral interactions in an achiral environment. Typically, SDE occurs in apolar mobile phases of weak elution strength, which causes the separation time to extend and the process productivity to deteriorate. To mitigate that effect, we altered the content of a strong solvent (modifier) in the mobile phase by use of a solvent gradient in which the target enantiomer was separated in the presence of the weak solvent, whereas the unresolved mixture of enantiomers was eluted by increasing the modifier content in the mobile phase. This enabled accelerating the solute elution while preserving the separation selectivity. The approach was examined for the separation of nonracemic mixtures of two structurally different compounds that exhibited the SDE effect in ACh, i.e., metalaxyl (MX) and methyl p-tolyl sulfoxide (MTSO). The target compound of the separation was the more abundant enantiomer in the enantiomeric mixture. The process realization was preceded by the determination of the effect of the modifier content on the separation yield for enantiomeric mixtures of MX and MTSO of different enantiomeric excess (ee). In the case of MX, yield of the pure target enantiomer varied from 2 %, for the maximum concentration of the modifier, to 45 % for the minimum modifier concentration and the largest ee used in the experiments. In the case of MTSO, the yield varied from minimum 40 % to maximum 66 %. To predict the process, we employed a dynamic model, in which underlying thermodynamic dependencies were implemented.

Charge-transfer complexation: A highly effective way towards chiral nanoparticles endowed by intrinsically chiral helicene and enantioselective SERS detection

An ordered chiral gold nanoparticle (AuNPs) array was prepared by the treatment of achiral sphere-shaped gold nanoparticles endowed with electron-accepting dinitro-phenyl (DNP) groups complexing with enantiomers of [6]helicene representing electron donors with strong chiroptical properties. Such surface-functionalization utilizes the principles of charge-transfer (CT) interaction. The incorporation of [6]helicene molecules with unique electronic and optical properties and subsequent arrangement of AuNPs caused chirality induction to intrinsically non-chiral plasmon-active nanostructures. The created nanostructures enabled the excitation of chiral plasmon and its application in highly sensitive enantioselective detection of small chiral molecules by surface-enhanced Raman spectroscopy (SERS). The chiral plasmonic response of such a system was shown to be fully controlled via the helicity of the parent [6]helicene. Upon calibration, it allowed us to directly determine the enantiomeric composition of non-racemic mixtures of (R)/(S)− 1-phenylethanol and (R)/(S)− 2-butanol.

Enantioseparation and mechanism study on baclofen by capillary electrophoresis and molecular modeling

Enantioselective analysis of chiral drugs plays a significant role in chemistry, biology and pharmacology. Baclofen, an antispasmodic chiral drug, has been widely studied due to the obvious differences in toxicity and medical activity between enantiomers. Herein, a simple and efficient method for separation of baclofen enantiomers by capillary electrophoresis was established without complicated sample derivatization and expensive instruments. Then, the molecular modeling and density functional theory were used to simulate and investigate the chiral resolution mechanism of electrophoresis, the calculated intermolecular forces were directly presented by visualization softwares. Moreover, the theoretical and experimental electronic circular dichroism (ECD) spectra of ionized baclofen were compared, and the configuration of dominant enantiomer in the nonracemic mixture can be determined by ECD signal intensity, which was proportional to the electrophoresis peak area difference of the corresponding enantiomer excess experiments. In this way, the peak order identification and configuration quantification of baclofen enantiomers in electrophoretic separation were successfully achieved without relying on a single standard.

Molecular Origins of Chiral Amplification on an Achiral Surface: 2D Monolayers of Aspartic Acid on Cu(111).

Recent experiments have demonstrated an intriguing phenomenon in which adsorption of a nonracemic mixture of aspartic acid (Asp) enantiomers onto an achiral Cu(111) metal surface leads to autoamplification of surface enantiomeric excess, ees, to values well above those of the impinging gas mixtures, eeg. This is particularly interesting because it demonstrates that a slightly nonracemic mixture of enantiomers can be further purified simply by adsorption onto an achiral surface. In this work, we seek a deeper understanding of this phenomena and apply scanning tunneling microscopy to image the overlayer structures formed by mixed monolayers of d- and l-Asp on Cu(111) over the full range of surface enantiomeric excess; ees = -1 (pure l-Asp) through ees = 0 (racemic dl-Asp) to ees = 1 (pure d-Asp). Both enantiomers of three chiral monolayer structures are observed. One is a conglomerate (enantiomerically pure), another is a racemate (equimolar mixture of d- and l-Asp); however, the third structure accommodates both enantiomers in a 2:1 ratio. Such solid phases of enantiomer mixtures with nonracemic composition are rare in 3D crystals of enantiomers. We argue that, in 2D, the formation of chiral defects in a lattice of one enantiomer is easier than in 3D, simply because the stress associated with the chiral defect in a 2D monolayer of the opposite enantiomer can be dissipated by strain into the space above the surface.

Separation of non-racemic mixtures of enantiomers by achiral chromatography

The phenomenon of partial separation of enantiomeric mixtures in achiral chromatography (ACh) has already been documented for a wide variety of chiral compounds. It is attributed to the so-called effect of self-disproportionation of enantiomers (SDE). However, quantitative description of the SDE mechanism underlying adsorption of enantiomers on achiral surfaces is still incomplete, which hinders the application of that technique for large-scale separations.In this study, a mechanistic model for description of retention behavior of SDE-phoric compounds in silica-based ACh has been developed along with a procedure for fast determination of the model parameters. The model assumes formation of associates of chiral molecules, which occurs due to homo and hetero-chiral interactions in the adsorbed phase. The ability of the model to reproduce band profiles was verified for enantiomeric mixtures of three structurally different chiral compounds.

Separation and identification of cetirizine enantiomers in human urine by capillary electrophoresis and circular dichroism independent of their standards.

Enantioseparation and determination of chiral drugs are of vital importance in biochemical and pharmaceutical research due to the different biological activity, mechanism, and toxicity of individual enantiomers. As a second-generation H(1)-antagonist, cetirizine's pharmaceutical activity is mainly derived from the levocetirizine while the dextro-enantiomer is ineffective and even associated with side effects. Herein, the enantiomers of cetirizine were separated by capillary electrophoresis and identified by electronic circular dichroism. Satisfactory linear relationship was found between the circular dichroism signal at λmax and the electrophoretic peak area difference in the nonracemic mixture of enantiomers. It made possible identification and quantification of cetirizine enantiomers independent of single enantiomer standards. The method's feasibility was demonstrated on the enantiomeric excess experiments of oral drugs measured in human blank urine. Additionally, the separation and determination of cetirizine in human urine afteradministration were also realized by capillary electrophoresis, indicating the method was sensitive enough for pharmacokinetic study.

19F NMR enantiodiscrimination and diastereomeric purity determination of amino acids, dipeptides, and amines.

Chiral amino-group compounds are of significance for human health, such as biogenic amino acids (AAs), dipeptides, and even various drugs. Enantiospecific discrimination of these chiral compounds is vital in diagnosing diseases, identifying pathological biomarkers and enhancing pharmaceutical chemistry research. Here, we report a simple and rapid 19F NMR-based strategy to differentiate chiral AAs, dipeptides, and amines, that were derivatized with (R)-2-(2-fluorophenyl)-2-hydroxyacetic acid ((R)-2FHA). As a result, 19 proteinogenic AAs (37 isomers) as well as Gly could be concurrently resolved. Moreover, various mirror-image dipeptides, such as Ser-His, Leu-Leu, and Ala-Ala, were commendably recognized. Intriguingly, we found that the absolute configuration of AAs in the N-terminus of dipeptides decided the relative 19F chemical shifts between two enantiomers. Besides, the ability of this method for enantiodiscrimination was further demonstrated by non-AA amines, including aromatic and aliphatic amines, and even amines having chiral centers several carbons away from the amino-group. The structurally similar antibiotics, amoxicillin and ampicillin, were well discriminated. Furthermore, this method accurately determines the de or dr values of non-racemic mixtures. Therefore, our strategy provides an effective approach for 19F NMR-based enantiodiscrimination and diastereomeric purity determination of amino-group compounds.

Pharmacological Profile of MP-101, a Novel Non-racemic Mixture of R- and S-dimiracetam with Increased Potency in Rat Models of Cognition, Depression and Neuropathic Pain.

The racemic mixture dimiracetam negatively modulates NMDA-induced glutamate release in rat spinal cord synaptosomal preparations and is orally effective in models of neuropathic pain. In this study, we compared the effects of dimiracetam, its R- or S-enantiomers, and the R:S 3:1 non-racemic mixture (MP-101). In vitro, dimiracetam was more potent than its R- or S-enantiomers in reducing the NMDA-induced [3H]D-aspartate release in rat spinal cord synaptosomes. Similarly, acute oral administration of dimiracetam was more effective than a single enantiomer in the sodium monoiodoacetate (MIA) paradigm of painful osteoarthritis. Then, we compared the in vitro effects of a broad range of non-racemic enantiomeric mixtures on the NMDA-induced [3H]D-aspartate release. Dimiracetam was a more potent blocker than each isolated enantiomer but the R:S 3:1 non-racemic mixture (MP-101) was even more potent than dimiracetam, with an IC50 in the picomolar range. In the chronic oxaliplatin-induced neuropathic pain model, MP-101 showed a significantly improved anti-neuropathic profile, and its effect continued one week after treatment suspension. MP-101 also performed better than dimiracetam in animal models of cognition and depression. Based on the benign safety and tolerability profile previously observed with racemic dimiracetam, MP-101 appears to be a novel, promising clinical candidate for the prevention and treatment of several neuropathic and neurological disorders.

Construction of CS/BSA multilayers for electrochemical recognition of tryptophan enantiomers

• A chiral interface based on chitosan (CS) and bovine serum albumin (BSA) was fabricated by simple self-assembly technique. • The chiral recognition of Trp enantiomers at (CS/BSA) 1.5 /GCE was demonstrated by DPV and contact angle measurements. • The percentage of L-Trp or D-Trp in a non-racemic mixture solution can be accurately predicted by (CS/BSA) 1.5 /GCE chiral interface. Ultra stable and reproducible electrochemical chiral interface ((CS/BSA) 1.5 /GCE) based on chitosan (CS) and bovine serum albumin (BSA) was fabricated using layer-by-layer (LbL) self-assembly technique. Its structure and properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and electrochemical methods. Snowflake like morphology was observed on the (CS/BSA) 1.5 films using SEM. Interestingly, the (CS/BSA) 1.5 chiral interface achieved chiral recognition of D-Trp and L-Trp via contact angle measurements. Under optimized experimental conditions, differential pulse voltammetry (DPV) results showed that the peak current ratio of D-Trp to L-Trp (I D /I L ) was 3.83 at (CS/BSA) 1.5 /GCE (glass carbon electrode). In addition, there was a good linear relationship between the peak current and Trp enantiomer concentration in the range of 0.005–0.15 mM. Our study shows the (CS/BSA) 1.5 /GCE can be used to quickly determine the ratio of enantiomers in non-racemic Trp mixture solutions, which is of great significance for the chiral recognition in non-racemic mixtures of chiral compounds.

Interconversion between OAM and SAM in five-wave mixing process in medium with the fourth-order optical susceptibility

We investigate the interconversion between spin components of the angular momentum (SAM) and orbital components of the angular momentum (OAM) of collinear elliptically polarized monochromatic fundamental beams with frequencies ω1 and ω2 in the five-wave mixing process in homogeneous isotropic nonracemic mixtures of chiral molecules with nonlinear fourth-order susceptibility. Fundamental beams have helicoidal wavefronts and arbitrary radial distributions of intensity. The discovered non-conservation of the total SAM and OAM projections on the direction of propagation of the interacting waves during the generation of radiation at the frequency 3ω1 - ω2 compensate each other, ensuring the conservation of the total angular momentum projection. A straightforward classical and quantum interpretation of the results is given.

An electrochemical chiral sensor based on competitive host-guest interaction for the discrimination of electroinactive amino acids.

A novel electrochemical chiral sensor has been designed based on the principle of competitive host-guest interaction and utilized for the discrimination of electroinactive proline (Pro) isomers. Electroactive methylene blue (MB) was used as the signal probe, which was combined with multi-walled carbon nanotubes (MWCNTs)-decorated β-cyclodextrin (β-CD), via host-guest interaction, where the oxidation peak currents of MB decreased after isomers of Pro were combined with the MWCNTs-β-CD via a competitive host-guest interaction. Due to the steric configuration of L-Pro matching the cavity of β-CD, more L-Pro than D-Pro was combined with MWCNTs-β-CD, resulting in a more pronounced decrease of MB peak currents. Therefore, the isomers of Pro could be discriminated. Besides Pro, the isomers of electroinactive histidine (His) could also be discriminated with the chiral sensor. In addition, the contents of L-Pro in non-racemic mixtures could be detected with the developed chiral sensor.

An Account of Chiral Metal Surfaces and Their Enantiospecific Chemistry

ConspectusMolecular chirality has been of scientific interest since 1848 when Pasteur demonstrated its direct connection to the rotation of light by solutions of chiral compounds. In the 1960s the connection was made between the chirality of pharmaceutical compounds and their physiological impact; one enantiomer can be therapeutic while the other is toxic. That realization prompted enormous effort in the synthesis of enantiomerically pure compounds for bioactive use (a $300B/yr market). Until relatively recently, metals were ignored as potential substrates for asymmetric surface chemistry because metals have highly symmetric, achiral bulk structures and the premise was that they could not expose chiral surfaces. In 1996, we demonstrated that the high Miller index surfaces of metals can be chiral, existing in two enantiomeric forms M(hkl)R&S, and we hypothesized that they exhibit enantiospecific interactions with chiral adsorbates. Most such intrinsically chiral metal surfaces have ideal structural motifs based on low Miller index terraces separated by kinked monatomic steps. This Account begins with a short tutorial on the ideal and real structures of chiral metal surfaces to provide a firm basis for understanding the origin of their chirality. It then chronicles the evolution of our understanding of their enantiospecific interactions with chiral adsorbates.Detecting, quantifying, and understanding enantiospecific surface chemistry on intrinsically chiral metal surfaces has been far more challenging than coming to the realization that such surfaces exist. The first successes came from measurements and modeling of the enantiospecific adsorption energetics of small chiral molecules such as propylene oxide and trans-1,2-dimethylcyclopropane. These revealed one of the core challenges to observing enantiospecificity, the fact that the enantiospecificities of reaction energetics and barriers tend to be small, i.e., a few kJ/mol. Measurements of the enantiospecific adsorption energetics of R-3-methylcyclohexanone on seven different Cu(hkl)R&S surfaces demonstrated their sensitivity to surface structure, but again revealed variations of only a few kJ/mol. One of the most important advances in our understanding of chiral surface chemistry is that the limitations imposed by weakly enantiospecific interactions can be circumvented by processes with nonlinear kinetics or equilibria. As an example, the surface explosion mechanism of d- and l-tartaric acid decomposition on Cu(hkl)R&S surfaces leads to enantiospecific rates that differ by almost 2 orders of magnitude, in spite of the fact that the rate constants are only weakly enantiospecific. More surprising is the observation that equilibrium adsorption of nonracemic mixtures of d- and l-aspartic acid can lead to autoamplification of enantiomeric excess, even on achiral Cu(111) surfaces. Again, this arises from a nonlinear adsorption isotherm. Most recently, we have developed a high throughput method for identification of the most enantiospecific surface orientation for a given reaction from the continuum of Cu(hkl)R&S surface orientations. These developments, and others described in this Account, firmly establish some of the basic principles of chiral surface chemistry.

High performance continuous-wave laser cavity enhanced polarimetry using RF-induced linewidth broadening.

We present precise optical rotation measurements of gaseous chiral samples using near-IR continuous-wave cavity-enhanced polarimetry. Optical rotation is determined by comparing cavity ring-down signals for two counter-propagating beams of orthogonal polarisation which are subject to polarisation rotation by the presence of both an optically active sample and a magneto-optic crystal. A broadband RF noise source applied to the laser drive current is used to tune the laser linewidth and optimise the polarimeter, and this noise-induced laser linewidth is quantified using self-heterodyne beat-note detection. We demonstrate the optical rotation measurement of gas phase samples of enantiomers of α-pinene and limonene with an optimum detection precision of 10 µdeg per cavity pass and an uncertainty in the specific rotation of ∼0.1 deg dm-1 (g/ml)-1 and determine the specific rotation parameters at 730 nm, for (+)- and (-)-α-pinene to be 32.10 ± 0.13 and -32.21 ± 0.11 deg dm-1 (g/ml)-1, respectively. Measurements of both a pure R-(+)-limonene sample and a non-racemic mixture of limonene of unknown enantiomeric excess are also presented, illustrating the utility of the technique.

Determination of the enantiomeric composition of amphetamine, methamphetamine and 3,4-methylendioxy-N-methylamphetamine (MDMA) in seized street drug samples from southern Germany.

Amphetamine (speed), methamphetamine (crystal meth), and 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) represent the most frequently abused amphetamine-type stimulants (ATS). Differences in pharmacological potency and metabolism have been shown for the enantiomers of all three stimulants. Legal consequences in cases of drug possession may also differ according to the German law depending on the enantiomeric composition of the seized drug. Therefore, enantioselective monitoring of seized specimens is crucial for legal and forensic casework. Various kinds of samples of amphetamine (n = 143), MDMA (n = 94), and methamphetamine (n = 528) that were seized in southern Germany in 2019 and 2020 were analyzed for their chiral composition using different chromatographic methods. Whereas all samples of amphetamine and MDMA were racemic mixtures, the chiral composition of the methamphetamine specimens was diverse. Although the vast majority (n = 502) was present as (S)-methamphetamine, also specimens containing pure (R)-methamphetamine (n = 7) were found. Furthermore, few samples (n = 8) were of racemic nature or contained non-racemic mixtures of both enantiomers (n = 10). Because methamphetamine appears in varying enantiomeric compositions, any seizure should be analyzed using an enantioselective method. Amphetamine and MDMA, on the other hand, currently appear to be synthesized exclusively via racemic pathways and are not chirally purified. Nevertheless, regular monitoring of the chiral composition should be ensured.

Rapid organocatalytic chirality analysis of amines, amino acids, alcohols, amino alcohols and diols with achiral iso(thio)cyanate probes.

The widespread occurrence and significance of chiral compounds does not only require new methods for their enantioselective synthesis but also efficient tools that allow rapid determination of the absolute configuration, enantiomeric composition and overall concentration of nonracemic mixtures. Although chiral analysis is a frequently encountered challenge in the chemical, environmental, materials and health sciences it is typically addressed with slow and laborious chromatographic or NMR spectroscopic techniques. We now show with almost 40 analytes representing 5 different compound classes, including mono-alcohols which are particularly challenging sensing targets, that this task can be solved very quickly by chiroptical sensing with a single, readily available arylisocyanate probe. The probe reacts smoothly and irreversibly with amino and alcohol groups when an organocatalyst is used at room temperature toward urea or carbamate products exhibiting characteristic UV and CD signals above 300 nm. The UV signal induction is not enantioselective and correlated to the total concentration of both enantiomers, the concomitant generation of a CD band allows determination of the enantiomeric composition from the same sample, and the sense of the induced Cotton effect reveals the absolute configuration by comparison with a reference. This approach eliminates complications that can arise when enantiomerically impure NMR derivatizing agents are used and it outperforms time-consuming HPLC protocols. The generation of distinct UV and CD signals at high wavelengths overcomes issues with insufficient resolution of overlapping signals often encountered with chiral NMR solvating agents that rely on weak binding forces. The broad solvent compatibility is another noteworthy and important characteristic of this assay. It addresses frequently encountered problems with insufficient solubility of polar analytes, for example pharmaceuticals, in standard mobile phase mixtures required for chiral HPLC analysis. We anticipate that the broad application spectrum, ruggedness and practicality of organocatalytic chiroptical sensing with aryliso(thio)cyanate probes together with the availability of automated CD multi-well plate readers carry exceptional promise to accelerate chiral compound development projects at reduced cost and with less waste production.

Enantioselective Recognition of Chiral Tryptophan with Achiral Glycine through the Strategy of Chirality Transfer.

Glycine (Gly), an achiral amino acid, has never been reported for enantioselective recognition owing to the absence of chiral sites. Herein, a facile strategy of chirality transfer is proposed to endow Gly with chirality. Optically active CuO, L-CuO, is first prepared, which can be used for the decoration of Gly through the formation of the Cu(Gly)2 complex. Successful chirality transfer from L-CuO to Gly is confirmed by circular dichroism (CD) spectra. The formation of the Cu(Gly)2 complex is further confirmed by Fourier transform infrared spectra and X-ray photoelectron spectroscopy. Next, the resultant L-CuO-Gly is used for chiral analysis of the isomers of tryptophan (Trp). Because of the higher affinity of L-CuO-Gly toward L-Trp than its isomer, the Trp isomers exhibit significant differences in their oxidation peak currents at the L-CuO-Gly-modified glassy carbon electrode (GCE) (IL-Trp/ID-Trp = 5.24). Finally, the practicability of the developed L-CuO-Gly/GCE is assessed, and the results indicate that it could be a reliable chiral sensor for the quantitative analysis of Trp isomers in nonracemic mixtures.

Enantiospecific equilibrium adsorption and chemistry of d-/l-proline mixtures on chiral and achiral Cu surfaces.

A fundamental understanding of the enantiospecific interactions between chiral adsorbates and understanding of their interactions with chiral surfaces is key to unlocking the origins of enantiospecific surface chemistry. Herein, the adsorption and decomposition of the amino acid proline (Pro) have been studied on the achiral Cu(110) and Cu(111) surfaces and on the chiral Cu(643)R&S surfaces. Isotopically labelled 1-13 C-l-Pro has been used to probe the Pro decomposition mechanism and to allow mass spectrometric discrimination of d-Pro and 1-13 C-l-Pro when adsorbed as mixtures. On the Cu(111) surface, X-ray photoelectron spectroscopy reveals that Pro adsorbs as an anionic species in the monolayer. On the chiral Cu(643)R&S surface, adsorbed Pro enantiomers decompose with non-enantiospecific kinetics. However, the decomposition kinetics were found to be different on the terraces versus the kinked steps. Exposure of the chiral Cu(643)R&S surfaces to a racemic gas phase mixture of d-Pro and 1-13 C-l-Pro resulted in the adsorption of a racemic mixture; i.e., adsorption is not enantiospecific. However, exposure to non-racemic mixtures of d-Pro and 1-13 C-l-Pro resulted in amplification of enantiomeric excess on the surface, indicative of homochiral aggregation of adsorbed Pro. During co-adsorption, this amplification is observed even at very low coverages, quite distinct from the behavior of other amino acids, which begin to exhibit homochiral aggregation only after reaching monolayer coverages. The equilibrium adsorption of d-Pro and 1-13 C-l-Pro mixtures on achiral Cu(110) did not display any aggregation, consistent with prior scanning tunneling microscopy (STM) observations of dl-Pro/Cu(110). This demonstrates convergence between findings from equilibrium adsorption methods and STM experiments and corroborates formation of a 2D random solid solution.

Enantioselective LC analysis and determination of selective serotonin reuptake inhibitors.

LC separation of biologically and pharmaceutically important enantiomers (from racemic or non-racemic mixtures) remains a subject of importance. The present review article deals with the liquid chromatographic enantioseparation of chiral selective serotonin reuptake inhibitors (SSRIs), namely citalopram, paroxetine, sertraline and fluoxetine. It is now known that the enantiomers of numerous psychotropic drugs exhibit distinct pharmacodynamics, pharmacokinetic patterns and receptor binding properties, and psychiatric patients are frequently taking more than one medication. Therefore, monitoring of the levels of these analytes in biological fluids is important to determine the levels of enantiomer concentrations; the present paper may be helpful in understanding the present state of available methods (along with a critical discussion of applicability of the methods) and in developing the new ones for this purpose. Different approaches using LC discussed herein may be applied for determining the enantiomeric composition (and enantiomeric purity) of SSRIs and numerous other racemic drugs, of current/future pharmaceutical importance and utility, using simple separation methods, instrumentation, inexpensive reagents and potentially significant analytical approaches. The contents cover the essential data to understand the various separation techniques and associated issues, if any, with documented examples.