Identification Of Enantiomers Research Articles

Electrochemical identification of reductive enantiomers in wood channels: A low-cost and scalable platform for chiral sensing

Chirality, an inherent characteristic of natural substances (such as sugars, peptides, proteins, and nucleic acid), plays a vital role in human metabolism and exerts substantial impacts. In general, chiral drugs can display diverse pharmacological and pharmacokinetic properties. One enantiomer may exhibit therapeutic effects, while the other could cause adverse reactions. Selective recognition of enantiomers is thus a significant task in the biomolecular and pharmaceutical fields. Despite the development of several chiral identification techniques, low-cost enantioselective sensing methods remain highly desirable. Here, we designed and developed an electrochemical sensing device for reductive enantiomer identification using natural wood channels as the substrate. The wood channels were endowed with oxidase-like activity through the in-situ growth of cerium oxide nanoparticles (CeO2). Chiral recognition capability was further introduced by incorporating a layer of chiral ZIF-8 (L-ZIF) as the chiral selector. To demonstrate the enantioselective sensing performance, 3,4-dihydroxyphenylalanine (DOPA) enantiomers were employed as model analytes. Due to the oxidase-like activity and the confinement effect of the proposed channels, the captured DOPA enantiomers were effectively oxidized to their quinone structure, and the Ce(IV) in CeO2 was reduced to Ce(III). These changes led to alterations in the surface charge of the channels, thereby modulating their ionic transport properties. This sensing mechanism also proved useful for the identification of other reductive enantiomers. The limits of detection for l-DOPA and d-DOPA were determined as 2.41 nM and 1.56 nM, respectively. The resulting wood channel-based sensing device not only can be used for the recognition and detection of reductive enantiomers, but also is expected to be applied to the non-electochemically active substances. Moreover, this study offers a novel type of solid-state channel material with low cost, reproducibility, and easy accessibility for electrochemical chiral sensing.

Helical au nanostructure for SERS detection of hazardous molecular and chiral enantiomers

In recent years, incidents of pesticide pollution and abuse of feed additives have occurred frequently, which pose a great threat to human health. Raman spectroscopy has become an important method in the field of food safety due to its rapidity, simplicity and sensitivity. It is important to obtain complex structure to promote surface-enhanced Raman scattering (SERS) effect. In this study, gold helical nanoparticles with rich surface structure were synthesized using cysteine as induce agent. Notably, the complex helical structure and tip led to an excellent electromagnetic enhancement property. The helical structure showed ultra-sensitive detection of hazardous molecular, such as thiram and ractopamine. Interestingly, the D/L-Au structure had significant chiral optical activity and could be used as an unlabeled SERS platform for enantiomer identification. This study provided an effective strategy for the detection of pesticides and feed additives, which could be applied in other aspects of food safety in the future.

Homochiral light-sensitive metal-organic framework photoelectrochemical gated transistor for enantioselective discrimination of monosaccharides

As pure antipodes may differ in biological interactions, pharmacology, and toxicity, discrimination of enantiomers is important in the pharmaceutical and agrochemical industries. Two major challenges in enantiomer determination are transducing and amplifying the distinct chiral-recognition signals. In this study, a light-sensitive organic photoelectrochemical transistor (OPECT) with homochiral character is developed for enantiomer discrimination. Demonstrated with the discrimination of glucose enantiomers, the photoelectrochemically active gate electrode is prepared by integrating Au nanoparticles (AuNPs) and a chiral Cu(II)-metal-organic framework (c-CuMOF) onto TiO2 nanotube arrays (TNT). The captured glucose enantiomers are oxidized to hydrogen peroxide (H2O2) by the oxidase-mimicking AuNPs-loaded c-CuMOF. Based on the confinement effect of the mesopocket structure of the c-CuMOF and the remarkable charge transfer ability of the 1D nanotubular architecture, variations in H2O2 yield are translated into significant changes in OPECT drain currents (ID) by inducing a catalytic precipitation reaction. Variations in ID confer a sensitive discrimination of glucose enantiomers with a limit of detection (LOD) of 0.07 μM for L-Glu and 0.05 μM for D-Glu. This enantiomer-driven gate electrode response strategy not only provides a new route for enantiomer identification, but also helps to understand the origin of the high stereoselectivity in living systems.

Synergetic Multichiral Covalent Organic Framework for Enantioselective Recognition and Separation.

In enantiomer recognition and separation, a highly enantioselective approach with universal applicability is urgently desired but hard to realize, especially in the case of chiral molecules. To resolve the trade-off between enantioselectivity and universality, a glutathione (GSH) and methylated cyclodextrins (MCD)-functionalized covalent organic framework (GSH-MCD COF) with porosity and abundant chiral surfaces is presented that was designed and synthesized for recognition and separation of various enantiomers. As expected, the GSH-MCD COF can be used as chiral stationary phases for the separation of various enantiomers, including aromatic alcohols, aromatic acids, amides, amino acids, and organic acids, with performance and versatility even superior to some widely used commercial chiral chromatographic columns. Furthermore, the synthesized GSH-MCD COF shows high enantioselectivity for the rapid recognition and identification of enantiomers and chiral metabolites when coupling to Raman spectroscopy. Molecular simulations suggest that the COF provides a confined microenvironment for cyclodextrins and peptides that dictates the separation and recognition capability. This work provides a strategy to synthesize synergetic multichiral COF and achieve separations and recognitions of enantiomers in complex samples.

Paper-based microfluidic system and chiroptical functionalized gold nano-oval for colorimetric detection of L-Tryptophan

“The development and deployment of a practical and portable technology for on-site chiral identification of enantiomers hold immense significance in the fields of medical and biological sciences. Among the essential amino acids, Tryptophan (Trp) plays a crucial role in human metabolism and serves as a diagnostic marker for various metabolic disorders. In this study, we introduce an innovative approach that combines an enantio-selective ZIF-8-His MOF-MIPs packed-bed centrifugal microfluidic system with an enantioselective colorimetric sensor probe. This system is further integrated with smartphone-based on-site data recording. The basis of this colorimetric sensor's operation lies in the controlled morphology and surface passivation of gold nano-ovals (Au–NOs) through DL-Alanine. To confirm the successful synthesis of the chiral recognition elements, we employed various characterization techniques, including FE-SEM, TEM, FTIR, CD, UV–Vis, zeta potential, DLS, and XRD. Our focus was on optimizing operational parameters for the effective separation and determination of L-chiral tryptophan on-site. The sensor exhibited two linear ranges for L-Trp detection: 0–5.42 and 5.42–80.47 mM, with a detection limit of 0.5 mM. The integrated system possesses advantages such as ease of availability, preparation, high stability, desirable selectivity even in the presence of similar biomolecules, and rapid detection capabilities. Furthermore, our method demonstrated successful enantioselective sensing of L-Trp in various biological samples, including human blood plasma, urine, milk, and bovine serum albumin (BSA), yielding promising results. The integrated microfluidic platform follows a "sample-in and answer-out" approach, making it highly applicable in healthcare, environmental monitoring, food safety analysis, and point-of-care testing. The chiral recognition pretreatment assay and self-contained, automated colorimetric detection on the microfluidic disc represent a promising avenue for cutting-edge research in these domains”.

Differentiation and identification of enantiomers by nuclear magnetic resonance spectroscopy with support of quantum mechanical computations.

We report nuclear magnetic resonance studies of two chiral building blocks of solifenacin, phenyltetrahydroisoquinoline and quinuclidinol, in which chiral solvating agents, Mosher's acid, and Pirkle's alcohol were used for spectral discrimination between enantiomers of solifenacin constituents. Based on the constraints following from measurements of the nuclear Overhauser effect, structures of phenyltetrahydroisoquinoline and Pirkle's alcohol solvates were found. Next, shifts of nuclear magnetic resonance signals of phenyltetrahydroisoquinoline due to the application of Pirkle's alcohol were computed using density functional theory methods. The computed carbon-13 shifts reproduce those determined experimentally, allowing us to attribute the absolute configuration to phenyltetrahydroisoquinoline enantiomers without the need for the use of empirical rules.

Spin‐Controlled Helical Quantum Sieve Chiral Spectrometer (Adv. Mater. 24/2023)

Identification of Chiral Enantiomers In article number 2209125, Hossam Haick and co-workers report a molecular-spin-sensitive-antenna (MSSA) made up of organically functionalized graphene layers on a fibrous helical cellulose network. The MSSA structure combines relativistic spin–orbit interaction coupled with organic spin-coherence and offers spatiotemporal chiral molecule separation, recognition, and selective identification of enantiomers. Coupled with neuromorphic artificial intelligence, it enables rapid classification of chiral molecules, resulting in portable spin-controlled spectrometry.

Water Evaporation-Driven Arginine Enantiomer Recognition on a Self-Powered Flexible Chip with High Specificity.

Chiral recognition is a crucial issue in the biomedical and pharmaceutical research communities. Due to the need for expensive equipment, reagents, and external energy, enantiomer identification is difficult to perform outside of a laboratory. Based on water evaporation-induced hydrovoltaic effect, a power-free sensing platform with sensitive chiral recognition capability is proposed for the discrimination of enantiomers. The chiral recognizer was bovine serum albumin (BSA), a naturally occurring protein. Using arginine (Arg) enantiomers as the sensing targets, the difference in enantioselectivity between l-Arg and d-Arg on a BSA-modified porous carbon substrate can be measured directly from the output voltage. By combining the cyclization reaction between NO and O-phenylenediamine (OPD), it has been discovered that the sensitivity and specificity of enantioselective identification can be significantly enhanced based on the surface charges. The limit of detection (LOD) could be as low as 76.0 nM. In addition, the proposed chips are extremely flexible and can function under deformation without sacrificing output performance. This self-powered chiral recognition chip paves a new path for the detection of chiral molecules at any time, any place, and it also has excellent potential for use in flexible wearable technology.

Chiral plasmonic Au–Ag core shell nanobipyramid for SERS enantiomeric discrimination of biologically relevant small molecules

The identification of enantiomers is of great importance in chiral separations and medicinal chemistry. While Surface-enhanced Raman spectroscopy (SERS) is a technique that provides vibrational fingerprints of analytes. The enantiomers identification relies on the SERS difference between left and right-handed circularly polarized light or additional selectors for indirect distinction. In this work, Au–Ag core shell nanobipyramid (L/D-Au@Ag BPs) were synthesized guiding by chiral encoder of L/D-cysteine. L/D-Au@Ag BPs produced plasmon-induced circular dichroism signals in the plasmon resonance absorption band, which can be tuned by modulation the amount of cysteine. Moreover, the chiral anisotropy factor of L/D-Au@Ag BPs at 532 nm can reach 5.11 × 10−3. Due to the selective resonance coupling between L/D-Au@Ag BPs and different enantiomers, L/D-Au@Ag BPs were further used as SERS substrates for efficient discrimination of biologically relevant small molecules. Chiral Au@Ag BPs display the potential for chiral drug identification.

All‐Dielectric Terahertz Metasurface with Giant Extrinsic Chirality for Dual‐Mode Sensing

Metasurface‐based sensors, with their planar compact structure and excellent sensing performance, have become one of the emerging technologies in metasurface and nanophotonics in recent years. In particular, chiral metasurfaces show unique advantages for chiral molecule detection and enantiomer identification. Herein, a scheme of dual‐mode sensing based on all‐dielectric terahertz metasurface via chiral and achiral spectroscopy is proposed. The proposed achiral meta‐atoms show great extrinsic chirality. The transmitted linearly polarized spectrum and the circular dichroism (CD) can be used as the sensing indicator under normal and oblique incidence of the terahertz waves, respectively. Among them, the working mode based on linear polarization spectrum only needs to measure the transmission spectrum once, which means wide applicability. The other mode using CD can eliminate the achiral terahertz absorption of the analyte through multiple measurements and has a higher signal‐to‐noise ratio. The results show that the maximum refractive index–frequency change rates of the two operating modes are −128.5 GHz/RIU and −124.7 GHz/RIU, respectively. In addition, there are two resonant peaks available in both working states, for both high‐precision and wide‐range refractive index detection. This new scheme is expected to be applied in industrial fields such as terahertz biochemical detection.

Self-Assembled Oligopeptide (FK)4 as a Chiral Alignment Medium for the Anisotropic NMR Analysis of Organic Compounds.

Anisotropic NMR parameters have been proven to be powerful for the structural elucidation of organic molecules. Herein, we present an alignment medium based on the self-assembled (FK)4 oligopeptide, showing excellent properties in measurements of anisotropic NMR parameters in both D2O and CD3OD. The preparation of the (FK)4-based alignment medium is simple and rapid. The low viscosity of the anisotropic phase makes it easy to be transferred to the NMR tube. The alignment of the oligopeptide is fast, stable, and homogeneous, with weak background signals, permitting the acquirement of high-quality NMR spectra. The performance of this alignment medium in residual dipolar coupling measurements and diastereomer discriminations is demonstrated by analyzing several different analytes. The enantiodiscrimination property of the (FK)4 oligopeptide is revealed by the difference of residual chemical shift anisotropy of the two enantiomers in the 1D 13C spectrum, granting its potential use for the quantification and identification of enantiomers of small molecules.

Locally superengineered cascade recognition-quantification zones in nanochannels for sensitive enantiomer identification.

As an intriguing and intrinsic feature of life, chirality is highly associated with many significant biological processes. Simultaneous recognition and quantification of enantiomers remains a major challenge. Here, a sensitive enantiomer identification device is developed on TiO2 nanochannels via the design of cascade recognition–quantification zones along the nanochannels. In this system, β-cyclodextrin (β-CD) is self-assembled on one side of the nanochannels for the selective recognition of enantiomers; CuMOFs are designed as the target-responsive partners on the other side of the nanochannels for the quantification of enantiomers that pass through the nanochannels. As a proof-of-principle of the cascade design, arginine (Arg) enantiomers are tested as the identification targets. The l-Arg molecules selectively bind in the recognition zone; d-Arg molecules pass through the recognition zone and then interact with the quantification zone via a specialized reduction reaction. As verified by nanofluidic simulations, because of the confinement effect of nanoscale channels combined with the condensation effect of porous structure, the in situ reaction in the quantification zone contributes to an unprecedented variation in transmembrane K+ flux, leading to an improved identification signal. This novel cascade-zone nanochannel membrane provides a smart strategy to design multifunctional nanofluidic devices.

Double-Layer Chiral System with Induced Circular Dichroism by Near-Field Coupling

Circular dichroism (CD) is widely used in enantiomer identification, photodetection, and circular polarization devices. Improving the CD signal of easily prepared 3D chiral nanostructures by design...

Engineering Homochiral MOFs in TiO2 Nanotubes as Enantioselective Photoelectrochemical Electrode for Chiral Recognition.

Enantioselective sensing of chiral molecules is an important issue for both biomedical research and the pharmaceutical industry. Here, an enantioselective photoelectrochemical (PEC) sensor was constructed by integrating TiO2 nanotubes (NTs) with metal-organic frameworks (MOFs) for the identification of enantiomers. TiO2 NTs prepared by electrochemical anodization can not only be used as the PEC platform but also as the metal-ion precursor to react with terephthalic acid (BDC) to form MIL-125(Ti) in situ. A postsynthetic exchange (PSE) method was used for exchanging the ligand of MIL-125 by 2-aminoterephthalic acid (BDC-NH2) for further functionalization. Homochirality was then successfully introduced into achiral MIL-125-NH2 by postsynthetic modification (PSM) with l-histidine (l-His). The resulting homochiral metal-organic frameworks (MOF)-in-NT architecture exhibits excellent discrimination ability for the chiral recognition of 3,4-dihydroxyphenylalanine (l/d-DOPA) enantiomers. Moreover, by adjusting the charge-carrier separation-induced photocurrent variation mechanism, the as-proposed homochiral PEC electrode exhibits a broad application potential for the discrimination of enantiomers. Because of the construction of binder-free monochiral MOF-in-NT structure directly on a Ti-metal substrate, the valuable feature is that the PEC sensing platform can be used directly, thereby providing a stable, simplified, and low-cost sensing device for the recognition of chiral enantiomers.

Microchemical identification of enantiomers in early-branching animals: Lineage-specific diversification in the usage of D-glutamate and D-aspartate

D-amino acids are unique and essential signaling molecules in neural, hormonal, and immune systems. However, the presence of D-amino acids and their recruitment in early animals is mostly unknown due to limited information about prebilaterian metazoans. Here, we performed the comparative survey of L-/D-aspartate and L-/D-glutamate in representatives of four phyla of early-branching Metazoa: cnidarians (Aglantha); placozoans (Trichoplax), sponges (Sycon) and ctenophores (Pleurobrachia, Mnemiopsis, Bolinopsis, and Beroe), which are descendants of ancestral animal lineages distinct from Bilateria. Specifically, we used high-performance capillary electrophoresis for microchemical assays and quantification of the enantiomers. L-glutamate and L-aspartate were abundant analytes in all species studied. However, we showed that the placozoans, cnidarians, and sponges had high micromolar concentrations of D-aspartate, whereas D-glutamate was not detectable in our assays. In contrast, we found that in ctenophores, D-glutamate was the dominant enantiomer with no or trace amounts of D-aspartate. This situation illuminates prominent lineage-specific diversifications in the recruitment of D-amino acids and suggests distinct signaling functions of these molecules early in the animal evolution. We also hypothesize that a deep ancestry of such recruitment events might provide some constraints underlying the evolution of neural and other signaling systems in Metazoa.

Separation of triacylglycerols containing allenic and acetylenic fatty acids by enantiomeric liquid chromatography-mass spectrometry

Triacylglycerols (TAGs) containing less common fatty acids (FAs) were isolated from the seeds of three plants (Santalum album, Crepis foetida, and Leucas aspera). These FAs had allenic (laballenic acid, Lb) and acetylenic (crepenynic, C; ximenynic acids, Xi) bonds. TAGs were analyzed on reversed-phase and chiral columns. High-resolution tandem mass spectrometry identified TAGs by positive electrospray ionization (ESI+). Twenty-two molecular species of TAGs isolated from the seed oil of Santalum album were separated by RP-HPLC and chiral HPLC methods and identified by positive electrospray ionization tandem MS detection (ESI+-MS). Two major enantiomers, i.e., sn-OOLb and sn-LLLb (O represents oleic acid; and L represents linoleic acid), were synthesized from the appropriate phosphatidylcholines. This allowed the identification of enantiomers after separation by chiral chromatography by tandem mass spectrometry. Similarly, TAGs from the seeds of Crepis foetida, and Leucas aspera were analyzed by reversed-phase chromatography and identified by mass spectrometry. Four enantiomers (sn-OOC, sn-LLC, sn-OOXi, and sn-LLXi) were synthesized. A total of six and three enantiomers of TAGs containing crepenynic and ximenynic acids, respectively, were identified by chiral column analysis. The retention times of TAGs containing allenic and acetylenic bonds were always greater on the reversed-phase column than TAGs with the same number of carbon atoms and the same unsaturation (e.g., LLL versus LLLb). From the chiral column, the regioisomers and enantiomers were eluted in the order of symmetric-asymmetric-asymmetric (i.e., sn-OCO, sn-COO, and sn-OOC). Through tandem mass spectrometry, we were able to identify and distinguish regioisomer [DAG]+-type ions, i.e., [MNH4NH3RCOOH]+, that can be considered diagnostic. Unfortunately, enantiomers and TAGs with the same numbers of carbon atoms and the same unsaturation levels have identical mass spectra, such as LLL and LLLb.

Enantiomeric separation of triacylglycerols containing fatty acids with a ring (cyclofatty acids)

Triacylglycerols (TAGs) containing cyclofatty acids (cycloFAs) from two oilseeds of Sterculia foetida and Hydnocarpus wightiana were analysed using both reversed-phase (RP18) and chiral phase columns. TAGs were identified using high-resolution electrospray ionization mass spectrometry in the positive ion mode. Fifty-five molecular species of TAGs have been identified in sterculic oil, 27 of which contained at least one cyclopropenyl-FA (e.g., malvalic or sterculic acids). The structures of regioisomers and enantiomers were determined for five major TAGs with cyclopropenyl-FAs.One hundred thirty-six TAGs were identified in chaulmoogra oil, 71 of which contained at least one cyclopentenyl-FA (e.g., gorlic, chaulmoogric, and hydnocarpic acids, etc.). Furthermore, in three molecular species, regioisomers and enantiomers were identified using HPLC on a chiral phase column. Eight molecular species of TAGs were prepared through organic synthesis to facilitate the identification of enantiomers. Retention times of fatty acid-containing triacylglycerols with one ring and one double bond are very similar to triacylglycerols with a dienoic fatty acid, but elution times are shorter. For example, dimalvaloylpalmitate elutes earlier than dilinoleylpalmitate.The order of elution of TAGs on the chiral column differs. In TAGs with 2 degrees of unsaturation (ring and double bond, e.g. PStP-StPP-PPSt), the order of elution is symmetric-asymmetric-asymmetric TAGs. TAGs with 4 degrees of unsaturation (one ring and three double bonds or two rings and two double bonds) present a different pattern. When TAGs contain two rings and two double bonds, the order of elution TAGs is asymmetric-symmetric-asymmetric (StStP-StPSt-PStSt); when TAGs contain a ring and 3 double bonds, the elution order is symmetric-asymmetric-asymmetric TAGs (OStO-StOO-OOSt). In species with a higher degree of unsaturation (e.g., 5), the elution order of the TAGs is asymmetric-asymmetric-symmetric (e.g. CCO-OCC-COC).

Electrically Programmable Terahertz Diatomic Metamolecules for Chiral Optical Control

Optical chirality is central to many industrial photonic technologies including enantiomer identification, ellipsometry-based tomography, and spin multiplexing in optical communications. However, a substantial chiral response requires a three-dimensional constituent, thereby making the morphology highly complex to realize structural reconfiguration. Moreover, an active reconfiguration demands intense dosage of external stimuli that pose a major limitation for on-chip integration. Here, we report a low bias, electrically programmable synthetic chiral paradigm with a remarkable reconfiguration among levorotatory, dextrorotatory, achiral, and racemic conformations. The switchable optical activity induced by the chiral conformations enables a transmission-type duplex spatial light modulator for terahertz single pixel imaging. The prototype delivers a new strategy towards reconfigurable stereoselective photonic applications and opens up avenues for on-chip programmable chiral devices with tremendous applications in biology, medicine, chemistry, and photonics.

Electrically Programmable Terahertz Diatomic Metamolecules for Chiral Optical Control.

Optical chirality is central to many industrial photonic technologies including enantiomer identification, ellipsometry-based tomography, and spin multiplexing in optical communications. However, a substantial chiral response requires a three-dimensional constituent, thereby making the morphology highly complex to realize structural reconfiguration. Moreover, an active reconfiguration demands intense dosage of external stimuli that pose a major limitation for on-chip integration. Here, we report a low bias, electrically programmable synthetic chiral paradigm with a remarkable reconfiguration among levorotatory, dextrorotatory, achiral, and racemic conformations. The switchable optical activity induced by the chiral conformations enables a transmission-type duplex spatial light modulator for terahertz single pixel imaging. The prototype delivers a new strategy towards reconfigurable stereoselective photonic applications and opens up avenues for on-chip programmable chiral devices with tremendous applications in biology, medicine, chemistry, and photonics.

A highly efficient chiral sensing platform for tryptophan isomers based on a coordination self-assembly

Construction of convenient and effective method for enantiomer identification is of vital significance for biochemistry and medical science. Herein, we design an effective sensor for chiral recognition of tryptophan (Trp) enantiomers, and self-assembly of Cu2+-modified β-cyclodextrin on poly-L-arginine/multi-walled carbon nanotubes (Cu-β-CD/PLA/MWCNTs) is studied. Meanwhile, Cu2+ acts as a cap to prevent the release of the high energy water and compel Trp enantiomer into the smaller opening of β-cyclodextrin. Recognition of L-Trp is accomplished by the formation of hydrogen bonds between the amino of L-Trp and the high energy water confined in cavity of Cu-β-CD. Compared with D-Trp, the sensor exhibits favorable chiral recognition toward L-Trp with a separation coefficient of 3.37. And the chiral sensor presents admirable enantiomers determination with excellent sensitivity, providing a good linear correlation in the range of 1 × 10−6 M~5.5 × 10−5 M, and the detection limit can reach 3.3 × 10−7 M (S/N = 3). Besides, the proposed sensor has been able to predict the percentage of D-Trp in the racemic mixture, suggesting its potential applications in the enantiomer recognition field.